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How to Cite a Case Study in APA, MLA, or Chicago

When citing a case study, the format in MLA and APA is similar to that of a report, and in Chicago style, it is similar to that of a book. For all three citation styles, you will need the name of the author(s), the title of the case study, the year it was published, the publishing organization/publisher, and URL (if applicable). The templates and examples below will demonstrate how to cite a case study in MLA, APA, and Chicago styles.

Author Last Name, Author First Name.  Title of Case Study . Edition (if applicable), volume number (if applicable), Publisher, year of publication, URL without http:// or https:// (if applicable).

Hill, Linda A., et al. HCL Technologies (A). Rev. edition, Harvard Business School, 2008, www.hbs.edu/faculty/Pages/item.aspx?num=34784.

In-text Citation:

(Author Last Name(s) page #)

(Hill et al. 8)

Author Last Name, Author Initial. (Publication Year). Title of Case Study (Case # if applicable). Publishing Organization. URL

Hill, L., Khanna, T., & Stecker, E. (2008). HCL Technologies (A) (Case 408-004). Harvard Business School. https://www.hbs.edu/faculty/Pages/item.aspx?num=34784

(Author Last Name, Publication Year)

(Hill et al., 2008)

Notes-bibliography style

Author Last Name, First Name.  Title of the Case Study . Publishing City: Publishing Organization, Publication Year. URL.

Hill, Linda A., Tarun Khanna, and Emily Stecker. HCL Technologies (A).  Boston: Harvard Business School, 2008. https://www.hbs.edu/faculty/Pages/item.aspx?num=34784.

1. Author First Name Last Name, Title of the Case Study (Publishing City: Publishing Organization, Publication Year), URL.

1. Linda A. Hill, Tarun Khanna, and Emily Stecker, HCL Technologies (A) ( Boston: Harvard Business School, 2008), https://www.hbs.edu/faculty/Pages/item.aspx?num=34784.

Author-date style

Author Last Name, First Name. Publication Year. Title of the Case Study . Publishing City: Publishing Organization. URL.

Hill, Linda A., Tarun Khanna, and Emily Stecker. 2008. HCL Technologies (A).  Boston: Harvard Business School. https://www.hbs.edu/faculty/Pages/item.aspx?num=34784.

In-text citation: 

(Author Last Name Publication Date)

(Holl, Khanna, and Stecker 2008)

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Published February 4, 2021. Updated August 9, 2021.

To create a reference or citation for a case study, you will need to know basic information including the name of the author, title of the case study, journal or book title, and publication year.

The templates and examples below will show you how to cite a case study in MLA style, APA style, Chicago style, and Harvard referencing style.

Easily cite a case study in the style of your choice using the  Chegg Writing citation generator .

Help protect your paper against accidental plagiarism with the Chegg Writing  plagiarism checker  and  citation generator .

Citing a case study in MLA style

In-text citation template and example:

(Author Surname Page number)

(Rapp and Caramazza 373)

Works cited entry template and example:

Surname, First M. “Title of the Case Study.”  Name of Publication , Volume number, Issue number, Publication Day Month Year, Page number. Case study.

Rapp, Brenda, and Alfonso Caramazza. “Selective Difficulties with Spoken Nouns and Written Verbs: A Single Case Study.”  Journal of Neurolinguistics , vol. 15, no. 3, 2002, pp. 373–402. Case Study.

Citing a case study in APA style

(Author Surname, Year)

(Rapp & Caramazza, 2002)

Reference list entry template and example:

Surname, F. M. (Publication Year). Title of the case study [Case study].  Name of Publication , Volume(Issue), Page number.

Rapp, B., & Caramazza, A. (2002). Selective difficulties with spoken nouns and written verbs: A single case study [Case study].  Journal of Neurolinguistics,  15(3), 373–402.

Citing a case study in Chicago style, notes-bibliography

Footnote template and example:

Author Full Name, “Title of the Case Study,”

Name of Publication

Volume number, Issue number (Publication Month Day, Year): Page number.

Brenda Rapp and Alfonso Caramazza, “Selective Difficulties with Spoken Nouns and Written Verbs: A Single Case Study,”

Journal of Neurolinguistics

15, no. 3 (2002): 373.

Shortened Note

Author Surname, “Shortened Title of the Case Study,” Page number.

Rapp and Caramazza, “Selective Difficulties,” 402.

Bibliography entry template and example:

Author Surname, First M. “Title of the Case Study.”  Name of Publication  Volume number, Issue number (Publication Month Day, Year): Page number.

Rapp, Brenda, and Alfonso Caramazza. “Selective Difficulties with Spoken Nouns and Written Verbs: A Single Case Study.”  Journal of Neurolinguistics  15, no. 3 (2002): 373–402.

Citing a case study in Chicago style, author-date

(Author Surname Publication year)

(Rapp and Caramazza 2002)

Author Surname, First M. Publication year. “Title of the Case Study.”  Name of Publication  Volume number, Issue number: Page number.

Rapp, Brenda, and Alfonso Caramazza. 2002. “Selective Difficulties with Spoken Nouns and Written Verbs: A Single Case Study.”  Journal of Neurolinguistics  15, no. 3: 373–402.

How to cite a case study in Harvard referencing style

(Author Surname, Publication Year)

(Rapp and Caramazza, 2002)

Author Surname, F.M. (Publication Year) ‘Title of case study’,  Name of Journal , Volume(Issue), pp. #-#.

Rapp, B. and Caramazza, A. (2002) ‘Selective difficulties with spoken nouns and written verbs: A single case study’,  Journal of Neurolinguistics , 15(3-5), pp. 373–402.

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APA Citation Guide (APA 7th Edition): Case Studies

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How to Write a Case Study in APA Format

Table of contents

• 1 What Is a Case Study In APA Format?
• 2.1 Sample Of APA Case Study Outline
• 3.1 Title Page in APA for Case Study Project
• 3.2 APA Title Page Example
• 3.3 The Abstract for an APA case study

Whether you study social sciences or life sciences, you’re likely to encounter a case study analysis in your academic journey. These papers demand a lot from students. First, you must have impeccable research and analysis skills. Sample populations, particularly people, can be challenging to analyze. It’s easy to misinterpret data and come up with the wrong conclusions. Additionally, you’ll need to have a knack for writing to present your findings persuasively, backed up by evidence-based arguments that build confidence for your teacher to accept the results of your work. If you need to boost your paper, Papers Owl is here to help you with a wide range of guidelines on how to write a case study in APA.

What Is a Case Study In APA Format?

To make your success, first realize that a case study is detective work. Your research may have an unresolved question or to carry out some testing to validate a hypothesis; in this case, studies are born. Psychology, nursing, and business are common fields this method is applied. In this scientific method, you’ll approach an event, action, individual, etc. And apply a set of circumstances to observe outcomes. Most papers in this field are written in the APA format, which can be a burden for students, especially if they aren’t familiar with this style. If you lack time or motivation for writing, appeal to our professional writers to write a case study  in APA format, and we will ensure your paper is perfectly formatted and gets a high grade.

Structure of Case Study Report In APA

First, let’s look at the sections in writing a case study in APA, which shares a few similarities to a typical research paper.

Introduction: Introduce your topic to the reader. Be sure to include the state of current research and where you plan to develop the current state of knowledge. You should include an interesting fact to reinforce your work’s importance and develop an interest in your hypothesis. Finish off with a thesis statement that you’ll focus on your workaround.

Aims: In this section, you answer the questions regarding why you are conducting your research and any questions you’ll explore. Avid case study writer recommends focusing your questions around your thesis. You can develop a triangle with a diagram and drill down your questions in a logical format that matches your paper’s main purpose.

Methods: Writing a case study in APA requires a methods section that details how you conducted your research. Did you conduct any interviews, send out questionnaires, or observe any behaviors? Detail them in this section, and state the environment and circumstances surrounding your data collection.

Results: Now that you’ve identified what you’d planned to accomplish and how you went about it in your APA case study format, it’s time to post the results. Don’t be shy if things don’t go swimmingly. Often in studies, we have unexpected results, which sometimes makes your paper more interesting to read.

Discussion: It’s time for the heart and soul of your paper. After all your research and observation, it is time to have a discourse on the results. The key to how to write a case paper in APA hangs on your ability to interpret the results in a meaningful way. Be sure to focus the discussion on your stated methods and how they pertain to your aims.

Recommendations: Here you want to detail what is to follow your research. Professional case study writers advise stating any knowledge gaps in your work and any unanswered or new questions you had found in the process. Your insights will be useful for others to follow in your footsteps and expand on your analysis.

Sample Of APA Case Study Outline

Example of writing a case study analysis in APA format:

Writing a case study in APA Step By Step

Knowing how to write a case study in APA format is a common question for students. In addition to the typical academic standards, APA has its own requirements that must be adhered to. The first step is to create a heading, known as a running head, that will be present on each page of your paper. The running head includes:

• The page number on the right margin
• A shortened title of your paper in ALL-CAPS no longer than 50 characters to the right

Title Page in APA for Case Study Project

The title of a case study in an APA paper is a requirement. The purpose is to state the name of the work, who the author is, and the institution that sponsored the research. It has the following parts:

• The words “running head” at the top, followed by the actual running head
• The full title of your paper using APA titling no longer than 12 words
• Your name without any designations (Dr/Ph.D./Rev/etc.) and the institution you attend

For APA Style ( 7th edition ), the cover page should also have:

• A page number at the top right corner.
• The institutional affiliation where the research took place.
• Course information, which is mandatory for student papers.
• The author’s note is optional and usually appears in professional papers.
• Font options have expanded to include Calibri 11, Arial 11, Lucida Sans Unicode 10, Times New Roman 12, or Georgia 11.
• All text on the title page should be double-spaced.
• Center all page contents and capitalize the first letter of significant words.

Note: APA 7 distinguishes between the formatting of title pages for professional and student papers. For instance, professional papers include a running head, while student papers do not necessarily include one.

APA Title Page Example

The Abstract for an APA case study

The abstract of your paper works as a summary to give a brief overview of what it contains. Include the running head at the top; the first line should have the word “abstract” centered. Follow the abstract with 150-250 words summarizing your paper. You may also index some keywords to help find the contents of your work in academic databases. At the end of your summary, indent once, and in italics, indicate keywords related to your work.

Writing an effective college paper requires a lot of planning and formatting to get it done right. Brush up on these guidelines for how to write your paper in APA format . If you need someone to review your work or write any parts of your paper, reach out to our professional writers, who are always willing to lend a hand.

Additionally, with the help of our blog, you can make sure you create a professional PowerPoint presentation that clearly outlines the main points of your paper. If you need help with this, our professional writers can provide guidance.

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How to Cite a Case Study

Last Updated: March 6, 2024

This article was co-authored by wikiHow staff writer, Jennifer Mueller, JD . Jennifer Mueller is a wikiHow Content Creator. She specializes in reviewing, fact-checking, and evaluating wikiHow's content to ensure thoroughness and accuracy. Jennifer holds a JD from Indiana University Maurer School of Law in 2006. This article has been viewed 37,525 times.

Particularly in research for business studies or papers in the social sciences, you may want to cite a case study completed by a university or other organization. While case studies have titles and publication information like other articles, they often have a unique case study number that is typically included in your citation. While Chicago citation style is most frequently used in business schools, you may also use the American Psychological Association (APA) or Modern Language Association (MLA) style.

Sample Citations

• Example: Lee, Stan.
• If there is more than one author, list the additional authors' names in first-middle initial-last format. Separate author's names with commas, with the word "and" before the last author's name.

• Example: Lee, Stan. "DC Comics in 2016." HBS No. 999-111.

• Example: Lee, Stan. "DC Comics in 2016." HBS No. 999-111. Boston: Harvard Business School Publishing, 2017.

• Example: Lee, Stan. "DC Comics in 2016." HBS No. 999-111. Boston: Harvard Business School Publishing, 2017. http://hbsp.harvard.edu, accessed July 2018.

• Print example: Stan Lee, "DC Comics in 2016," HBS No. 999-111 (Boston, Harvard Business School Publishing, 2017), p. 14.
• Online example: Stan Lee, "DC Comics in 2016," HBS No. 999-111 (Boston, Harvard Business School Publishing, 2017), http://hbsp.harvard.edu, accessed July 2018.

• Example: Lee, S.
• Separate the names of multiple authors with commas, placing an ampersand before the last author's name.

• Example: Lee, S. (2017).
• If there is no year of publication listed, use the abbreviation "n.d." in the parentheses.

• Example: Lee, S. (2017). DC Comics in 2016 .

• Example: Lee, S. (2017). DC Comics in 2016 . HBS No. 999-111.

• Example: Lee, S. (2017). DC Comics in 2016 . HBS No. 999-111. Boston, MA: Harvard Business School Publishing.

• Example: (Lee, 2017).

• If there are 2 authors, place the word "and" between their names. For 3 or more, use commas with the word "and" before the final author. After the first author, list subsequent authors with their first name followed by their last name. For example: Lee, Stan and Clark Kent.

• Example: Lee, Stan. DC Comics in 2016. Case Study.

• Example: Lee, Stan. DC Comics in 2016. Case Study. Boston. Harvard Business School Publishing, 2017.
• Note that unlike many other citation styles, the unique case study number is not necessarily included for MLA citations. Ask your instructor or supervisor if they want this information included in your citation.

• Print example: Lee, Stan. DC Comics in 2016. Case Study. Boston. Harvard Business School Publishing, 2017. Print.
• Web example: Lee, Stan. DC Comics in 2016. Case Study. Boston. Harvard Business School Publishing, 2017. Web. 17 July 2018.
• If you accessed the case study online, you may put the URL of the case study. However, this isn't required by MLA style. Ask your instructor or supervisor for their preference.

• Example: (Lee 27).

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• ↑ https://guides.library.ualberta.ca/apa-citation-style/case-studies
• ↑ http://libanswers.snhu.edu/faq/128490
• ↑ http://libanswers.walsh.edu/faq/147917
• ↑ http://maag.guides.ysu.edu/businesscitations/mla

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Last Updated: Jun 22, 2023 Views: 75063

When citing case studies in APA style you'll want to include the typical citation elements and apply general formatting guidelines. The following are examples of how case studies could be cited in APA style, but be sure to check with your professor about how they'd like you to cite case studies in your work.

In-Text Citations

Kotter (1990) explains the steps British Airways took to reverse a horrible customer service atmosphere and financial crisis.

… as the case study concluded (Bisell & Tram, 2007) .

Groysberg and Connolly (2015) concluded in their case study that….

Reference List

Example (don't forget to indent the second and subsequent lines):

Author(s). (Year). Title of case study . HBS No. number of case study. Publisher.

Example, one author:

Kotter, J. (1990). Changing the culture at British Airways . HBS No. 491-009. Harvard Business School Publishing.

Example, two authors:

Groysberg, B., & Connolly, K. (2015). BlackRock: Diversity as a driver for success . HBS No. 415-047. Harvard Business School Publishing.

More Information

• APA Guide  (Shapiro Library)
• APA Style Blog This link opens in a new window (APA)

Further Help

This information is intended to be a guideline, not expert advice. Please be sure to speak to your professor about the appropriate way to cite sources in your class assignments and projects.

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To access Academic Support, visit your Brightspace course and select “Tutoring and Mentoring” from the Academic Support pulldown menu.

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To access help with citations and more, visit the Academic Support via modules in Brightspace:

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Harvard Referencing Style: Case Studies & Standards

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Referencing Case Studies

IN-TEXT CITATION

Spar and Burns (2000) ...

.... (Spar & Burns, 2000)

"....." (Spar & Burns, 2000:8)

FORMAT OF A REFERENCE TO A CASE STUDY

Author’s surname, Initials. Year. ‘Title.’ Case number. Place: Publisher or Institution.

Note that the title is not italicised.

EXAMPLE OF A REFERENCE TO A PRINTED CASE STUDY

Spar, D. and Burns, J. 2000. ‘Hitting the wall: Nike and International Labor Practices.’ HBS 700047.  Boston: Harvard Business School Publishing.

EXAMPLE OF A REFERENCE TO AN ELECTRONIC CASE STUDY FROM A DATABASE

Mathu, K.M. and Scheepers, C . 2016.  'L eading change towards sustainable green coal mining'. Available from: Emerald Emerging Markets Case Studies, < https://www.emeraldinsight.com/doi/full/10.1108/ EEMCS-01-2016-0007> [Accessed on: 7 June 2017].

Referencing Standards

South African Bureau of Standards (2013) ...

... (South African Bureau of Standards, 2013).

"....." (South African Bureau of Standards, 2013: 3).

FORMAT OF A REFERENCE  TO A STANDARD

Name of the Authorizing Body. Year.  Number and Title of Standard.  Place of Publication: Publisher.

 EXAMPLE OF A REFERENCE TO A PRINT STANDARD

British Standards Institute.2015.  ​BS ISO 14001:Environmental management systems. Requirements with guidance for use.  ​London: British Standards Institute.

EXAMPLE OF A REFERENCE  TO AN ELECTRONIC STANDARD TAKEN FROM A DATABASE

South African Bureau of Standards. 2013.  SANS 1300​: Quality management — Customer satisfaction — Guidelines for monitoring and measuring ​. [online]. Pretoria: South African Bureau of Standards. Available from:<https://www.sabs.co.za/Standardss/index.asp> [ Accessed on: 17 March 2014].

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How do I cite a case study?

According to APA, case studies do not have their own citation style or process, instead a case study is typically cited according to its source type -- often as an article. See below for some examples.

Journal Article/Case Study with DOI (Print or Electronic)

Author Last Name, First Initial. Second Initial.(Year). Title of article. Journal Title , Volume Number (Issue Number), Page Numbers. http://dx.doi.org/xx.xxxxxxx.xx.x

Wheeler, B. J., & Taylor, B. J. (2012). Successful management of allergy to the insulin excipient metacresol in a child with type 1 diabetes: a case report.  Journal Of Medical Case Reports ,  6 (1), 263-266. http://dx.doi.org/10.1186/1752-1947-6-263

Case Study with a DOI from a Library Database (not from a Journal)

Author Last Name, First Initial. Second Initial. (Year). Title of article. Publisher . http://dx.doi.org/xx.xxxxxxx.xx.x

Example from SAGE Cases:

Ravichandran, N., & Narayanaswami, S. (2016). Security management at the national institute of management: To outsource or insource? (A). SAGE Publications . https://www.doi.org/10.4135/9781526438379

Journal Article/Case Study Without a DOI from a Library Database

Author Last Name, First Initial. Second Initial., & Author Last Name, First Initial. Second Initial. (Year). Title of article. Journal Title, Volume Number (Issue Number), Page Numbers. Permanent link/URL

Pedemont, K., Jolly, N., & Rose, L. (2011). A child with Myasthenia Gravis and defective accommodation: A case study.  Australian Orthoptic Journal ,  43 (2), 4–8.  https://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,shib&db=a9h&AN=87023984&site=eds-live&custid=s9076023

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How to Cite a Case Study: A Detailed Guide

Table of Contents

It’s no news that one of the most difficult things about any academic assignment is formatting. And while choosing fonts and margins is easy, citing and referencing can be a problem. If you also wonder how to cite a case study, this article is the right place to be.

We want to tell you about the most common referencing styles and the way you should use them. In a few minutes, you’ll know how to reference a case study. Just save the post or print it and be ready for any task and requirement!

Citing a Case Study With Our Help

Many students don’t know how to cite a case study. They study tones of books and manuals, but the guidelines constantly change. That is why it becomes very difficult to cite case study in a proper way. In any case, if you do not have a desire or time, use  case study writing service  and get a discount for the first order!

Some of them decide to use free online platforms where you insert information and get a reference in return. But there is no guarantee that the case study citation will be correct. To achieve the best results, you should turn to CaseStudyWritingService.com. Our experts and their tips have already changed the lives of thousands of students. So why don’t you give it a try?

How to cite a case study in APA

If you don’t know how to cite a case study in APA, here is a general format to consider: 

Author. (Year). Case study title. Case study number. URL.

Utah Sociology School Case Study

Williams, N. (2019). Society. GFH No. 8-912-283. https://gfh.utah.edu/cases/

As you see, an APA citation case study is rather easy to reference.

How to cite a case study MLA

For those who wonder how to cite a case study MLA examples and tips below are very useful:

Last name, first name. Title. Edition, volume number, publisher, publication year, URL without HTTPS

MLA citation case study example:

Smith, Anna, et al. VR Technologies. Rev. edition, Utah Sociology School, 2015, www.vr.edu/faculty/pages/num=21042.

How to cite a case study in a Book

Here’s how to cite a case study in a book:  Author. (Year). Case study title. Case study number.

As you see, a book citation case study is very similar to the APA style.

How to cite a case study in ACS

ACS citation case study has the following format:

Last name, First name. Case study Title. Edition, volume number, publisher, publication year. Case study.

When learning how to cite a case study in ACS, don’t forget about punctuation and capital letters.

How to cite a case study in AMA

To understand how to cite a case study in AMA, you just need to look at the common template below:

• Last name, First name of the author. Title. Abbreviated Title. Year Month Day; volume and issue: pages.

The AMA citation case study is quite different from others, so you should bear the structure above in mind.

How to cite a case study in ASA

ASA citation case study format is very simple: Author. Publication Year. Title.

Here’s an example of how to cite a case study in ASA:

Jackson. 2008. Smith Co Ltd.

How to cite a case study in IEEE

Here’s how the IEEE citation case study format looks like:

Author’s last name, Case Study Title. City, State, Country: Publisher’s name, Month Day, Year.

An example of how to cite a case study in IEEE:

Leonard, Our response to global warming. New York, NY, USA: Printed Press, Sept. 14, 2015.

How to cite a case study in Harvard

Harvard citation case study format includes the following elements:

Author. Publication year. Title. Date viewed. URL in &lt;&gt;

Example of how to cite a case study in Harvard:

Willis. 2009. The Man I Have Become. Viewed 13 March 2010, &lt;http://willis.com/blog-post/the-man-I-have-become/&gt;

Requirements for this style change rather often, so not to miss a thing, you should get the latest updates from recent sources.

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• Case studies

General format

There is no specific way to reference a case study in APA style. Case studies are typically published as an article or report, or within a book. Format the reference list entry according to the type of publication. Following are some examples of case studies in business.

Business case study

Author(s). (Year).   Title of case study . Number of case study. URL

Harvard business school case study

Dey, A. (2022). Corporate governance: A three pillar framework. HBS No. 491-009.  https://hbsp.harvard.edu/cases/

Ivey business school case study

Dunbar, C., & Southam, C. (2005). London youth symphony. Ivey ID: 9B05009.  http://iveycases.com

Style notes

• If the case study is not numbered, leave it out of the reference entry.
• If the source is a book, format the reference according to the rules for books.
• If the source is a journal, format the reference according to the rules for journal articles.
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How to Cite a Case Study in APA: A Comprehensive Guide

If you’re writing an academic paper, you may need to cite a case study. But how do you do that? This guide will explain everything you need to know about citing a case study in APA format.

Table of Contents

What is APA?

APA stands for American Psychological Association. It is a style guide used by many academic disciplines, including psychology, sociology, and business. The purpose of the APA style is to provide a consistent format for academic writing, making it easier for readers to understand and follow the author’s argument.

Why is it important to cite a case study?

Citing a case study is important for several reasons. First, it gives credit to the original author for their work. Second, it allows readers to find the source if they want to learn more. Finally, it adds credibility to your work by demonstrating that you have researched and referenced other relevant studies.

How to cite a case study in APA format

Here are the steps you need to follow to cite a case study in APA format:

Step 1: Start with the author’s last name and first initial.

The first step in citing a case study is to list the author’s last name and first initial. For example Smith, J.

Step 2: Include the year of publication in parentheses.

Next, you need to include the year of publication in parentheses. For example: (2018).

Step 3: Provide the title of the case study in italics.

After the year of publication, you need to provide the title of the case study in italics. For example The impact of social media on adolescent mental health.

Step 4: Add the name of the publisher.

The next step is to add the name of the publisher. For example Harvard Business Review Press.

Step 5: Include the DOI or URL.

Finally, you need to include the DOI or URL where the case study can be found. For example https://doi.org/10.1145/1234567.1234567

Here’s what the final citation should look like:

Smith, J. (2018). The impact of social media on adolescent mental health. Harvard Business Review Press. https://doi.org/10.1145/1234567.1234567

What to do if there is no DOI or URL

If you cannot find a DOI or URL for the case study, you can omit it from the citation. In that case, you should include the name of the database where you found the case study instead. For example:

Smith, J. (2018). The impact of social media on adolescent mental health. Harvard Business Review Press. Academic Search Complete.

Tips for citing a case study in APA format

• Always check the specific requirements of your instructor or publisher to ensure that you are following their guidelines correctly.
• Double-check your citations to make sure that you have included all the necessary information.
• If you are citing multiple case studies from the same author or publisher, you can use a shortened version of the citation after the first one. For example Smith (2018, p. 25).

Citing a case study in APA format may seem daunting at first, but it is quite simple once you know the steps. By following the guidelines in this article, you can ensure that your citations are accurate and complete and that you are giving credit to the original authors for their work.

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Answer Last Updated: Aug 23, 2023     Views: 19856

Author's Last Name, Author's First Name. "Title of Case Study." Case Study Number (if given), Publisher, Year of Publication.  Database Name . Case Study.

Havard, Cody T. " Basketball at the Most Magical Place on Earth: A Case Study of the NBA’s Season Conclusion at Walt Disney World Amid the COVID-19 Pandemic." SAGE, 2021.  SAGE Business Cases . Case Study.   

  According to APA, case studies do not have their own citation style or process, instead, cite as an article. 

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• How to cite a court case in APA Style

How to Cite Court Cases in APA Style | Format & Examples

Published on February 4, 2021 by Jack Caulfield . Revised on December 27, 2023.

Legal citations (e.g. court cases, laws ) in APA Style look somewhat different from other APA citations. They generally don’t list authors, and abbreviations are used to make them more concise.

Citations for court cases refer to reporters , the publications in which cases are documented. To cite a court case or decision, list the name of the case, the volume and abbreviated name of the reporter, the page number, the name of the court, the year, and optionally the URL.

The case name is italicized in the in-text citation, but not in the reference list. In the reference, specify only a single page number—the page where the coverage of that case begins—instead of a full page range.

You can easily create citations for court cases using our free  APA Citation Generator .

Table of contents

Abbreviations in apa legal citations, citing federal court cases, citing state court cases, frequently asked questions about apa style citations.

Most words are abbreviated in legal citations. This means that a very large number of standard abbreviations exist. Consult resources like this page to familiarize yourself with common abbreviations.

Pages where case information is found online also tend to show the correct form of citation for the case in question. You can check these to make sure you use the right abbreviations.

Note that “v.” (for “versus”) is used between the names of the parties in a case title, though APA recommends “vs.” outside the context of legal citations.

Are your APA in-text citations flawless?

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Federal court cases are those that take place at the national level in the U.S.—in the U.S. Supreme Court, a circuit court, or a district court.

U.S. Supreme Court

The Supreme Court is the highest federal court, and its decisions are reported in the United States Reports (abbreviated to “U.S.” in the reference). You don’t need to specify the court in parentheses in this case, since the name of the reporter already makes this clear.

Circuit court

Decisions from the U.S. circuit courts are reported in the Federal Reporter . This reporter has appeared in three series; the first is abbreviated as “F.”, the second as “F.2d”, and the third and current series as “F.3d”.

There are 13 circuit courts, so specify which one you’re citing in the parentheses, e.g. “9th Cir.”

District court

Decisions from the U.S. district courts are reported in the Federal Supplements.  Like the Federal Reporter , it has appeared in three series, abbreviated as “F. Supp.”, “F. Supp. 2d”, and “F. Supp. 3d”.

There are many different district courts, so specify which one is being cited in the parentheses, e.g. “N.D. Ohio.”

State courts are those that operate in specific states rather than federally. The two kinds of state court that are commonly cited are supreme courts and appellate courts. They are both cited in a similar format.

In APA Style , when you’re citing a recent court case that has not yet been reported in print and thus doesn’t have a specific page number, include a series of three underscores (___) where the page number would usually appear:

With APA legal citations, it’s recommended to cite all the reporters (publications reporting cases) in which a court case appears. To cite multiple reporters, just separate them with commas in your reference entry . This is called parallel citation .

Don’t repeat the name of the case, court, or year; just list the volume, reporter, and page number for each citation. For example:

No, including a URL is optional in APA Style reference entries for legal sources (e.g. court cases , laws ). It can be useful to do so to aid the reader in retrieving the source, but it’s not required, since the other information included should be enough to locate it.

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the “Cite this Scribbr article” button to automatically add the citation to our free Citation Generator.

Caulfield, J. (2023, December 27). How to Cite Court Cases in APA Style | Format & Examples. Scribbr. Retrieved June 24, 2024, from https://www.scribbr.com/apa-examples/court-case/

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How to Cite a Case Study: Different Styles

November 20, 2023

Properly citing case studies plays a crucial role in academic writing for several reasons. Firstly, citing case studies demonstrates the credibility and reliability of your arguments and research. By referencing the original sources, you show that you have conducted thorough research and have used reputable and authoritative information to support your claims.

Secondly, citing case studies allows readers to further explore the topic and verify the information provided. It enables them to locate and read the full case study if they wish to delve deeper into the details and findings. This promotes transparency and fosters a more comprehensive understanding of the subject matter.

Finally, citing case studies acknowledges the contributions of the original authors and researchers. By giving proper credit, you adhere to ethical standards of academic integrity and avoid plagiarism. It also ensures that the individuals responsible for the case study receive recognition for their work.

In summary, citing case studies is essential in academic writing to enhance credibility, facilitate further exploration, and acknowledge the original authors’ contributions.

Basic Guidelines for Citing a Case Study

When citing a case study in your essay, it is important to follow some basic guidelines to ensure accuracy and consistency. Here are the key guidelines to keep in mind:

• Identify the case study: Start by providing the full title of the case study, along with the names of the authors or researchers involved. Include any relevant publication information, such as the name of the journal or book in which the case study is published.
• Format the citation style: Depending on the citation style required by your academic institution or professor, format your case study citation accordingly. Common citation styles include APA, MLA, Chicago, and Harvard. Each style has specific rules for formatting and referencing case studies, so familiarize yourself with the requirements of the chosen style.
• Include the case study publication date: In addition to the authors’ names and title, mention the date on which the case study was published. This provides important chronological context for your readers and allows them to assess the relevance and currency of the information presented.
• Provide a direct link or source: Whenever possible, include a direct link or source to the case study. This could be a URL to an online version of the case study, a DOI (Digital Object Identifier), or the volume and page numbers if it is published in a journal or book. This helps readers locate the case study easily and access it for further reading.

By adhering to these basic guidelines, you can ensure that your case study citations are accurate, consistent, and accessible for your readers. Remember to consult the specific guidelines of your chosen citation style to ensure complete adherence.

Citing a Case Study in APA Format

When citing a case study in APA format, follow these guidelines to accurately reference the source:

• Author(s) of the case study: Include the last name(s) and initials of the author(s) of the case study. If there are multiple authors, separate their names with commas and use an ampersand (&) before the last author’s name.
• Year of publication: Provide the year the case study was published in parentheses.
• Title of the case study: Use sentence case capitalization for the title. Only capitalize the first word and proper nouns.
• Source information: Depending on the source type, include additional details following the title. For example:
• If it is a journal article, include the journal name in italics, volume number(issue number), and page range.
• If it is a book chapter, include the book title in italics and the editors’ names.
• If it is an online source, provide the URL and the date of access.

Example APA citation for a case study:

• Single author: Author, A. (Year). Title of case study. Source information.
• Multiple authors: Author, A., & Author, B. (Year). Title of case study. Source information.

Make sure to properly format the citation, including hanging indents, use of italics, and punctuation. Additionally, list all the case studies you cited in a separate references page at the end of your essay, following APA formatting guidelines.

Citing a Case Study in MLA Format

When citing a case study in MLA format, follow these guidelines to reference the source accurately:

• Authors of the case study: Include the author’s name(s) in the order they appear in the source, but inverted (last name, first name).
• Title of the case study: Use sentence case capitalization. Capitalize the first word, proper nouns, and any other words that would normally be capitalized. Italicize the title.
• Title of the source: Use italics to indicate the title of the source. This could be the name of the journal, book, or website.
• Publication information: Depending on the source type, include additional details following the source title. For example:
• If it is a journal article, include the name of the journal in italics, volume number (issue number), and page range.
• If it is a book chapter, include the book title in italics, the editors’ names, publisher, year of publication, and page range.
• If it is an online source, provide the name of the website in italics, the date of publication, the name of the publisher, the URL, and the date of access.

Example MLA citation for a case study:

• Single author: Author last name, First name. “Title of case study.” Title of source, Publication information.
• Multiple authors: Last name, First name and First name Last name. “Title of case study.” Title of source, Publication information.

Remember to properly format the citation, including hanging indents, use of italics, and punctuation. Additionally, list all the case studies you cited in a separate works cited page at the end of your essay, following MLA formatting guidelines.

Citing a Case Study in Chicago Style

When citing a case study in Chicago style, follow these guidelines to reference the source accurately:

• Title of the case study: Use sentence case capitalization. Capitalize the first word, proper nouns, and any other words that would normally be capitalized. Enclose the title in double quotation marks.

Example Chicago citation for a case study:

• Single author: Author last name, first name. “Title of case study.” In Title of source, publication information.
• Multiple authors: Last name, first name, and first name last name. “Title of case study.” In Title of source, publication information.

Remember to properly format the citation, including hanging indents and punctuation. Additionally, list all the case studies you cited in a separate bibliography page at the end of your essay, following Chicago formatting guidelines.

Citing a Case Study in Harvard Style

When citing a case study in Harvard style, follow these guidelines to accurately reference the source:

• Authors of the case study: Include the last name(s) and initials of the author(s) of the case study. Separate multiple authors’ names with commas and use an ampersand (&) before the last author’s name.
• Title of the case study: Use sentence case capitalization for the title. Capitalize the first word, proper nouns, and any other words that would normally be capitalized. Italicize the title.

Example Harvard citation for a case study:

Ensure the citation is properly formatted, including punctuation, use of italics, and indentation. Also, list all the case studies cited in a separate references list at the end of the essay, following Harvard formatting guidelines.

Online Databases for Finding Case Studies

Finding case studies for your essay is made easier with the availability of online databases. These databases compile various case studies from different disciplines, allowing you to access a wide range of relevant examples. Here are some online databases you can use to find case studies:

• Google Scholar : This widely-used search engine provides access to scholarly articles, including case studies. Use specific keywords to narrow down your search and include the phrase “cite a case study” to find articles that specifically discuss how to cite case studies.
• EBSCOhost : EBSCOhost is a popular online research platform that offers access to multiple databases such as Academic Search Complete, Business Source Complete, and Psychology and Behavioral Sciences Collection. These databases contain numerous case studies across various fields.
• JSTOR : JSTOR is a digital library that provides access to academic journals, books, and primary sources. It covers diverse disciplines and includes a vast collection of case studies that can be useful for your research.
• ProQuest : ProQuest is another comprehensive research tool that offers access to a wide range of databases, including scholarly journals, newspapers, and dissertations. It houses a substantial collection of case studies covering multiple subject areas.

When searching in these databases, use keywords specific to your topic, such as the name of the industry or concept you are focusing on. Additionally, if you find a relevant case study, make sure to cite it correctly using the appropriate citation style.

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How to Write a Case Study - All You Wanted to Know

What do you study in your college? If you are a psychology, sociology, or anthropology student, we bet you might be familiar with what a case study is. This research method is used to study a certain person, group, or situation. In this guide from our dissertation writing service , you will learn how to write a case study professionally, from researching to citing sources properly. Also, we will explore different types of case studies and show you examples — so that you won’t have any other questions left.

What Is a Case Study?

A case study is a subcategory of research design which investigates problems and offers solutions. Case studies can range from academic research studies to corporate promotional tools trying to sell an idea—their scope is quite vast.

What Is the Difference Between a Research Paper and a Case Study?

While research papers turn the reader’s attention to a certain problem, case studies go even further. Case study guidelines require students to pay attention to details, examining issues closely and in-depth using different research methods. For example, case studies may be used to examine court cases if you study Law, or a patient's health history if you study Medicine. Case studies are also used in Marketing, which are thorough, empirically supported analysis of a good or service's performance. Well-designed case studies can be valuable for prospective customers as they can identify and solve the potential customers pain point.

Case studies involve a lot of storytelling – they usually examine particular cases for a person or a group of people. This method of research is very helpful, as it is very practical and can give a lot of hands-on information. Most commonly, the length of the case study is about 500-900 words, which is much less than the length of an average research paper.

The structure of a case study is very similar to storytelling. It has a protagonist or main character, which in your case is actually a problem you are trying to solve. You can use the system of 3 Acts to make it a compelling story. It should have an introduction, rising action, a climax where transformation occurs, falling action, and a solution.

Here is a rough formula for you to use in your case study:

Problem (Act I): > Solution (Act II) > Result (Act III) > Conclusion.

Types of Case Studies

The purpose of a case study is to provide detailed reports on an event, an institution, a place, future customers, or pretty much anything. There are a few common types of case study, but the type depends on the topic. The following are the most common domains where case studies are needed:

• Historical case studies are great to learn from. Historical events have a multitude of source info offering different perspectives. There are always modern parallels where these perspectives can be applied, compared, and thoroughly analyzed.
• Problem-oriented case studies are usually used for solving problems. These are often assigned as theoretical situations where you need to immerse yourself in the situation to examine it. Imagine you’re working for a startup and you’ve just noticed a significant flaw in your product’s design. Before taking it to the senior manager, you want to do a comprehensive study on the issue and provide solutions. On a greater scale, problem-oriented case studies are a vital part of relevant socio-economic discussions.
• Cumulative case studies collect information and offer comparisons. In business, case studies are often used to tell people about the value of a product.
• Critical case studies explore the causes and effects of a certain case.
• Illustrative case studies describe certain events, investigating outcomes and lessons learned.

Need a compelling case study? EssayPro has got you covered. Our experts are ready to provide you with detailed, insightful case studies that capture the essence of real-world scenarios. Elevate your academic work with our professional assistance.

Case Study Format

The case study format is typically made up of eight parts:

• Executive Summary. Explain what you will examine in the case study. Write an overview of the field you’re researching. Make a thesis statement and sum up the results of your observation in a maximum of 2 sentences.
• Background. Provide background information and the most relevant facts. Isolate the issues.
• Case Evaluation. Isolate the sections of the study you want to focus on. In it, explain why something is working or is not working.
• Proposed Solutions. Offer realistic ways to solve what isn’t working or how to improve its current condition. Explain why these solutions work by offering testable evidence.
• Conclusion. Summarize the main points from the case evaluations and proposed solutions. 6. Recommendations. Talk about the strategy that you should choose. Explain why this choice is the most appropriate.
• Implementation. Explain how to put the specific strategies into action.
• References. Provide all the citations.

How to Write a Case Study

Let's discover how to write a case study.

Setting Up the Research

When writing a case study, remember that research should always come first. Reading many different sources and analyzing other points of view will help you come up with more creative solutions. You can also conduct an actual interview to thoroughly investigate the customer story that you'll need for your case study. Including all of the necessary research, writing a case study may take some time. The research process involves doing the following:

• Define your objective. Explain the reason why you’re presenting your subject. Figure out where you will feature your case study; whether it is written, on video, shown as an infographic, streamed as a podcast, etc.
• Determine who will be the right candidate for your case study. Get permission, quotes, and other features that will make your case study effective. Get in touch with your candidate to see if they approve of being part of your work. Study that candidate’s situation and note down what caused it.
• Identify which various consequences could result from the situation. Follow these guidelines on how to start a case study: surf the net to find some general information you might find useful.
• Make a list of credible sources and examine them. Seek out important facts and highlight problems. Always write down your ideas and make sure to brainstorm.
• Focus on several key issues – why they exist, and how they impact your research subject. Think of several unique solutions. Draw from class discussions, readings, and personal experience. When writing a case study, focus on the best solution and explore it in depth. After having all your research in place, writing a case study will be easy. You may first want to check the rubric and criteria of your assignment for the correct case study structure.

Read Also: ' WHAT IS A CREDIBLE SOURCES ?'

Although your instructor might be looking at slightly different criteria, every case study rubric essentially has the same standards. Your professor will want you to exhibit 8 different outcomes:

• Correctly identify the concepts, theories, and practices in the discipline.
• Identify the relevant theories and principles associated with the particular study.
• Evaluate legal and ethical principles and apply them to your decision-making.
• Recognize the global importance and contribution of your case.
• Construct a coherent summary and explanation of the study.
• Demonstrate analytical and critical-thinking skills.
• Explain the interrelationships between the environment and nature.
• Integrate theory and practice of the discipline within the analysis.

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Case Study Outline

Let's look at the structure of an outline based on the issue of the alcoholic addiction of 30 people.

Introduction

• Statement of the issue: Alcoholism is a disease rather than a weakness of character.
• Presentation of the problem: Alcoholism is affecting more than 14 million people in the USA, which makes it the third most common mental illness there.
• Explanation of the terms: In the past, alcoholism was commonly referred to as alcohol dependence or alcohol addiction. Alcoholism is now the more severe stage of this addiction in the disorder spectrum.
• Hypotheses: Drinking in excess can lead to the use of other drugs.
• Importance of your story: How the information you present can help people with their addictions.
• Background of the story: Include an explanation of why you chose this topic.
• Presentation of analysis and data: Describe the criteria for choosing 30 candidates, the structure of the interview, and the outcomes.
• Strong argument 1: ex. X% of candidates dealing with anxiety and depression...
• Strong argument 2: ex. X amount of people started drinking by their mid-teens.
• Strong argument 3: ex. X% of respondents’ parents had issues with alcohol.
• Concluding statement: I have researched if alcoholism is a disease and found out that…
• Recommendations: Ways and actions for preventing alcohol use.

Writing a Case Study Draft

After you’ve done your case study research and written the outline, it’s time to focus on the draft. In a draft, you have to develop and write your case study by using: the data which you collected throughout the research, interviews, and the analysis processes that were undertaken. Follow these rules for the draft:

Use Data to Illustrate Key Points in Your Case Study

Even though your case study is a story, it should be based on evidence. Use as much data as possible to illustrate your point. Without the right data, your case study may appear weak and the readers may not be able to relate to your issue as much as they should. Let's see the examples from essay writing service :

‍ With data: Alcoholism is affecting more than 14 million people in the USA, which makes it the third most common mental illness there. Without data: A lot of people suffer from alcoholism in the United States.

Try to include as many credible sources as possible. You may have terms or sources that could be hard for other cultures to understand. If this is the case, you should include them in the appendix or Notes for the Instructor or Professor.

Finalizing the Draft: Checklist

After you finish drafting your case study, polish it up by answering these ‘ask yourself’ questions and think about how to end your case study:

• Check that you follow the correct case study format, also in regards to text formatting.
• Check that your work is consistent with its referencing and citation style.
• Micro-editing — check for grammar and spelling issues.
• Macro-editing — does ‘the big picture’ come across to the reader? Is there enough raw data, such as real-life examples or personal experiences? Have you made your data collection process completely transparent? Does your analysis provide a clear conclusion, allowing for further research and practice?

Problems to avoid:

• Overgeneralization – Do not go into further research that deviates from the main problem.
• Failure to Document Limitations – Just as you have to clearly state the limitations of a general research study, you must describe the specific limitations inherent in the subject of analysis.
• Failure to Extrapolate All Possible Implications – Just as you don't want to over-generalize from your case study findings, you also have to be thorough in the consideration of all possible outcomes or recommendations derived from your findings.

How to Create a Title Page and Cite a Case Study

Let's see how to create an awesome title page.

Your title page depends on the prescribed citation format. The title page should include:

• A title that attracts some attention and describes your study
• The title should have the words “case study” in it
• The title should range between 5-9 words in length
• Your name and contact information
• Your finished paper should be only 500 to 1,500 words in length.With this type of assignment, write effectively and avoid fluff

Here is a template for the APA and MLA format title page:

There are some cases when you need to cite someone else's study in your own one – therefore, you need to master how to cite a case study. A case study is like a research paper when it comes to citations. You can cite it like you cite a book, depending on what style you need.

Citation Example in MLA ‍ Hill, Linda, Tarun Khanna, and Emily A. Stecker. HCL Technologies. Boston: Harvard Business Publishing, 2008. Print.

Citation Example in APA ‍ Hill, L., Khanna, T., & Stecker, E. A. (2008). HCL Technologies. Boston: Harvard Business Publishing.

Citation Example in Chicago Hill, Linda, Tarun Khanna, and Emily A. Stecker. HCL Technologies.

Case Study Examples

To give you an idea of a professional case study example, we gathered and linked some below.

Eastman Kodak Case Study

Case Study Example: Audi Trains Mexican Autoworkers in Germany

To conclude, a case study is one of the best methods of getting an overview of what happened to a person, a group, or a situation in practice. It allows you to have an in-depth glance at the real-life problems that businesses, healthcare industry, criminal justice, etc. may face. This insight helps us look at such situations in a different light. This is because we see scenarios that we otherwise would not, without necessarily being there. If you need custom essays , try our research paper writing services .

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What Is A Case Study?

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is a seasoned educational writer focusing on scholarship guidance, research papers, and various forms of academic essays including reflective and narrative essays. His expertise also extends to detailed case studies. A scholar with a background in English Literature and Education, Daniel’s work on EssayPro blog aims to support students in achieving academic excellence and securing scholarships. His hobbies include reading classic literature and participating in academic forums.

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Search the FAQ

How do i cite a case study in harvard business review.

Cite case study as you cite a book.

EasyBib: https://www.easybib.com/guides/citation-guides/how-do-i-cite-a/case-study/

University od Alberta: https://guides.library.ualberta.ca/apa-citation-style/case-studies

• Citation Format
• Last Updated Apr 14, 2020
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Citation guides

All you need to know about citations

How to cite “The art of case study research” by Robert E. Stake

Apa citation.

Formatted according to the APA Publication Manual 7 th edition. Simply copy it to the References page as is.

If you need more information on APA citations check out our APA citation guide or start citing with the BibguruAPA citation generator .

Stake, R. E. (1995). The art of case study research . SAGE Publications.

Chicago style citation

Formatted according to the Chicago Manual of Style 17 th edition. Simply copy it to the References page as is.

If you need more information on Chicago style citations check out our Chicago style citation guide or start citing with the BibGuru Chicago style citation generator .

Stake, Robert E. 1995. The Art of Case Study Research . Thousand Oaks, CA: SAGE Publications.

MLA citation

Formatted according to the MLA handbook 9 th edition. Simply copy it to the Works Cited page as is.

If you need more information on MLA citations check out our MLA citation guide or start citing with the BibGuru MLA citation generator .

Stake, Robert E. The Art of Case Study Research . SAGE Publications, 1995.

Other citation styles (Harvard, Turabian, Vancouver, ...)

BibGuru offers more than 8,000 citation styles including popular styles such as AMA, ASA, APSA, CSE, IEEE, Harvard, Turabian, and Vancouver, as well as journal and university specific styles. Give it a try now: Cite The art of case study research now!

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This is not the edition you are looking for? Check out our BibGuru citation generator for additional editions.

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• Online image or video
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What Is Cite This For Me’s APA Citation Generator?

If you are working on a paper in the APA style, you know that formatting APA citations can be a complicated task that requires a lot of patience. Fortunately, referencing has never been so easy. Introducing your new best friend: the Cite This For Me APA citation generator. Using this automated citation machine to create accurate citations allows students to work smarter, leaving them more time to focus on their studies.

The Cite This For Me powerful citation generator fully-formats all of your APA citations in just a click. So if you’re unsure how to accurately create your citations in the APA format, or you need to cite all of your sources in record time, using the Cite This For Me accurate generator will help ensure you don’t lose valuable points on your work unnecessarily.

This guide provides you with everything you need to know to help ensure that your paper reflects all your hard work. Read ahead for tips on how to structure and present your work according to the APA formatting guidelines, how to avoid charges of plagiarism, and how to cite sources both in-text and in your reference list and bibliography.

Popular APA Citation Examples

• Dictionary entry 
• Edited book 
• Image or video online
• PDF or E-book
• Presentation or lecture
• Video, film, or DVD

Why Do I Need to Cite?

Essentially, citing is the crediting of sources used in academic work. When another source contributes to your work you must acknowledge the original author with an accurate reference, unless it is common knowledge (e.g., the Magna Carta was signed in 1215). Failing to cite all of your sources or citing them incorrectly constitutes plagiarism , which is considered a serious academic offense. It is important to remember that information doesn’t just belong to anyone who happens to stumble upon it. If you are caught plagiarizing it is more than likely that you will lose points on your assignment, or even face expulsion from your university.

APA citation format also stipulates that students and researchers should be wary of a type of plagiarism called “self-plagiarism.” This is when you reuse material that you previously wrote for a new writing assignment without signaling to the reader that you have done so by creating an APA format citation for your work. Presenting your own past work as new scholarship is still plagiarism, and could still have serious consequences.

Aside from avoiding plagiarism, attributing your research to its proper source is crucial in ensuring that your work is firmly anchored in academic tradition. Correctly citing your sources validates the statements and conclusions you make in your work by providing supporting evidence. For many students, citing can be a frustrating process, but it’s an excellent way to enhance the quality of your work and inject it with authority.

Imagine if all the stress of referencing simply vanished. Well, Cite This For Me’s APA citation generator is here to help you make that stress disappear – now you can create in-text citations and reference lists in the APA format without all of the usual frustrations of referencing.

What is the APA Citation Style?

The APA citation style is a parenthetical author-date style, meaning that you need to put the author’s last name and the publishing date into parentheses wherever another source is used in the narrative.

The APA format consists of in-text citations and a reference list, along with guidelines for formatting the paper itself. Both the in-text citations and the reference list can be created in the blink of an eye using the Cite This For Me APA reference generator.

Although primarily used by students and researchers studying the social and behavioral sciences, the APA format is used amongst other scientific publications for its editorial efficiency. The Cite This For Me APA citation generator uses an up to date version of the APA format, helping to ensure accuracy whether you are using the APA format generator for university assignments or are preparing research projects for publishing.

Aside from the APA format, there is a plethora of different citation styles out there – the use of which depends on your discipline, university requirements, your professor’s preference, or the publication you are submitting the work to. It is important to make sure that you are using the correct style – so if you’re unsure, consult your department and follow their guidelines exactly.

It is important to note that APA style citation rules are fundamentally an editorial style, not a writing style per se. An editorial style refers to rules and guidelines a publisher uses to ensure that materials in their publications are presented consistently.

The citation generator above will generate your references in APA format as standard, and can show you how to cite APA sources in a few clicks. You can also sign up to Cite This For Me to select from thousands of widely used global college styles, including individual university variations. So, whether your professor prefers that you use the MLA format , or your discipline requires you to adopt the Chicago style citation , your referencing will be supported. Cite This For Me includes citation generators and handy guides for styles such as ASA , AMA or IEEE .

How Do I Create and Format My Citations?

Ever find yourself searching the web for things like “How to cite a website APA?” Then you’re in the right place. When you reference a source within an APA style paper; whether it is using a direct quote, repurposing an image, or simply referring to an idea or theory, you should:

• Insert an in-text citation (the author’s surname and the date of publication within parentheses) straight after a direct quote
• Insert an in-text citation at the end of the sentence where a source has contributed, but was not a direct quote
• If you have already mentioned the author’s name in the sentence, you only need to insert the date immediately after their surname
• Include page numbers within the parentheses (after the date), if referring to a particular page or section of the source
• When citing a source with three to five authors, include all surnames for the first in-text citation, then use the first author’s surname followed by et al. for subsequent citations
• When citing six or more authors – use the first author’s surname followed by et al. for all citations
• If you are mentioning both the year and author in the text, don’t include an additional citation in parentheses – unless you are referring to a particular section of the source, in which case you should cite the page number
• Provide an alphabetical list (ordered by author’s surname) of all sources used, titled ‘References’, on a separate page at the end of the narrative
• Inclusive page numbers for the electronic version of a print source (i.e., a PDF)
• Provide your appendices on a separate page after the reference list
• Use ‘&’ in place of ‘and’ in both in-text citations and full references

Use the Cite This For Me APA citation maker to create citations with ease; this will allow you to add citations to your project, edit on the spot, and export separate in-text citations as well as fully-formatted reference lists.

APA Citation Examples (7th Edition)

Each APA reference must adhere to the rules set forth in the Publication Manual of the American Psychological Association, 7th edition . The following examples follow guidelines from Chapter 10 of the manual. Here are a few examples for you to get started:

In-text citation APA examples:

• Page specified, author mentioned in text:

Lutz & Huitt (2010, p. 4) argue that “the statistical significance of …”

• Page specified, author not mentioned in text:

The results were consistent throughout the study (Fernández-Manzanal, Rodríguez-Barreiro, & Carrasquer, 2007).

• Six authors:

The study found that … (Sania et al., 2011)

The data presented …. (“How sleep enhances memory retention”, 2015).

Reference list examples:

• Book citation, one author, multiple editions:

Hawking, S. W. (1998). A brief history of time: From the big bang to black holes (10th ed.). New York: Bantam Doubleday Dell Publishing Group.

• Ebook, online only:

Tyler, G. (n.d.). Evolution in the systems age . Retrieved from http://www.onlineoriginals.com/showitem.asp?itemID=142&action=setvar&vartype=history&varname=bookmark&v1=1&v2=46&v3=2

• Journal article, three authors, with a DOI:

Fernández-Manzanal, R., Rodríguez-Barreiro, L., & Carrasquer, J. (2007). Evaluation of environmental attitudes: Analysis and results of a scale applied to university students. Science Education , 91(6), 988–1009. doi:10.1002/sce.20218

* Note: For more information on the different types of journal article citations that can be made under APA 7, see section 10.1 of the Publication Manual, pp. 316-321.

• How to cite a website in APA:

Veterans Affairs Canada. (2019, February 14). Indigenous people in the Second World War . https://www.veterans.gc.ca/eng/remembrance/history/historical-sheets/aborigin

• Online newspaper article:

Smith, D. (2019, October 22). The banner, the rings, the season opener: Champion Raptors return on a night like no other. The Toronto Star . https://www.thestar.com/sports/raptors/2019/10/22/the-banner-the-rings-the-season-opener-champion-raptors-return-on-a-night-like-no-other.html

• Article from an online news website (HuffPost, MSNBC, Vox, etc.):

Wade, L. (2013, March 6). ‘Sunstone’ crystal from British shipwreck may be vikings’ legendary navigation aid . HuffPost. https://www.huffpost.com/entry/sunstone-british-shipwreck-viking-navigation_n_2818858

• Video, online:

CrashCourse. (2015, April 30). Mars: Crash course astronomy #15 [Video]. YouTube. https://www.youtube.com/watch?v=I-88YWx71gE

How Do I Format My Reference List?

Drawing on a range of relevant sources in your work proves that you have read widely around your chosen topic, so it’s a surefire way to impress your reader.

To ensure your reader’s ease of comprehension you must adhere to the style’s formatting guidelines. In APA format, a list of all the sources that have directly contributed to your work should be placed on a new page at the end of the narrative and titled ‘References’ (center align the title), otherwise known as an APA works cited list. The references should all have a hanging indentation – the second and subsequent lines of each reference should start ½ inch from the margin.

You may also be required to provide a full APA bibliography. This is a comprehensive list of all the source material you used to complete the assignment, even if it was not cited in the text. It should include any book, journal, article etc. that you may have consulted throughout your research and writing process in order to get a deeper understanding of the subject at hand.

APA Format Example:

Sound like a lot of work? Although the style guidelines are strict in regard to how references should be formatted, the Cite This For Me APA citation machine can help take the weight off your shoulders by quickly compiling your reference list and bibliography.

APA Style Paper Formatting Guidelines (7th Edition)

When following the APA format guidelines, you must pay attention to presentation details such as font type, line spacing, margins and page headers to ensure your work is easily legible. The information below, as well as further formatting details, can be found in Chapter 2 of the APA 7 Publication Manual .

• 1-inch margins on all sides
• Easily readable font – Times New Roman recommended, 12pt. size
• Double-space the entirety of the paper
• Page numbers in the header, aligned to the right
• Title of the paper in all capitals, 50 characters or less, in the header on each page of the body (the ‘running head’), aligned to the left. Only include a running head if you’re writing a professional paper
• The paper should typically include four major sections – Title Page, Abstract, Main Body and References.
• If infographics (tables, charts) were used in the narrative you should also add Appendices as a separate section at the end of the paper.

APA Title Page

Not all instructors will require a title page, also sometimes called an APA cover page. If they do, include these four parts:

• Title of your paper
• Running head (see above section)
• Author’s/Your name
• Institutional affiliation

The title of your paper should:

• Be centered on the page and use title case (a combination of lower and uppercase letters).
• Not be italicized, bolded, or underlined
• Use a 12-point font
• Be a maximum of 2 lines and not more than 12 words long
• Not include abbreviations

Underneath the title, place the author’s name. If you wrote the paper, put your full name here. There’s no need to include titles or degrees (e.g., Ms., PhD, etc.).

Under the author’s name, place the institutional affiliation. For most students, this would be the name of the school, college or university you are attending. The title, author’s name, and institutional affiliation should all be double spaced. Here’s an example of an APA format title page:

Writing Guidelines

The American Psychological Association also provides some helpful guidelines regarding overall best practices when writing academic and scientific papers. One important thing to be on the lookout for is bias in your writing. For instance, using the word “man” to represent humans as a species is neither scientific nor without potential bias.

Here are some good rules of thumb to help you avoid bias in your paper:

• Always be specific in your writing and avoid generalizations.
• Do not label people or test subjects unnecessarily.
• When writing about participants in your experiment or study, be sure to acknowledge them as such appropriately. Use the term “participants” instead of “subjects.”
• Use active voice instead of passive voice in your writing. For example, “the participants completed the task” vs. “the task was completed by the participants.”
• Always be cautious when discussing topics such as sexual orientation, racial and ethnic identity, disabilities, etc.
• Never change quotations to better serve your own ends or to better fit with your conclusions.

Important Terms for an APA Paper

Have you come across terms such as “abstract” or “appendices” in the manual and been unsure of their meanings? Here are some important terms to know when writing your next APA paper.

• Abstract – A brief and concise summary of your paper’s contents.
• Keywords – A list of significant keywords that the reader should be on the lookout for in your paper.
• Introduction – Generally kicks of the rest of your paper by describing what you’re writing about. In scientific papers, this would outline the problem you are solving and your research strategy.
• References – An APA reference page is the place where you list each source that you have cited via an APA in-text citation within the body of your paper.
• Running Head – Running head is the name of APA headings that are used in research papers. They contain the title of the paper, the page number, and the term “Running head.”

A Brief History of the APA Format

APA stands for American Psychological Association , the scientific organization that assembles the publishing manual of the APA format. The style was developed in 1929 by a group of scientists to standardize scientific writing. It was created in the hopes that it would provide a coherent and professional manner of citing sources for students and researchers in the fields of social and behavioral sciences.

The first publication manual of the APA format was published in pursuit of a neat and efficient research formatting style, mainly for editorial purposes. Although some contemporary scientists argued that having such strict regulations restricted personal writing styles, the format has since become one of the most popular referencing styles. Today it is adopted in term papers, research reports, literature reviews, theoretical articles, case studies etc.

What’s New in the 7th Edition of APA Format?

It is important to note that citation styles and referencing formats change over time as they adapt to new source types and trends in academic publishing. APA format is no different, and in the fall of 2019 released the 7th edition of its Publication Manual.

Are you curious to know what the differences are between the 7th and 6th edition of APA style? Here are some of the important updates listed in the 7th edition of APA citing:

• The location of the source’s publisher no longer needs to be included in the citation.
• DOIs are formatted as URLs (i.e. https://doi.org/xxx), and no longer require the label “DOI” preceding them in the reference.
• When making an APA website citation, URLs no longer need to be preceded by “Retrieved from.” The exception to this is when you include a date of retrieval, which is optional.
• When making an APA book citation for an ebook, you no longer need to include the device or platform that you read the book on (i.e. “Kindle) is no longer required in the citation.
• There is more flexibility in the 7th edition regarding APA paper format specifications on font.
• The running head in an APA format title page no longer requires the words “Running head,” and instead now only requires a page number and a shortened version of your paper’s title.
• You now need to only use one space after each period in your paper.

Before you switch to the newest version, it is a good idea to confirm with your teacher or instructor that this is the version of the style that they prefer you use.

How do I Create Accurate Citations with the Cite This For Me APA Generator?

Referencing giving you a headache? Let the Cite This For Me APA format generator remove the stress caused by citations by helping to turn in any of your sources into a fully-formatted citation. The generator will create your reference in two parts; an in-text citation and a full reference that is ready to be copied straight into your work.

To unlock the full potential of the APA citation maker, simply login to Cite This For Me multi-platform tool. Use the web platform to add and edit citations, export full projects and individual entries, utilize the add-ons, and save all of your citations in the cloud. Or, you can make use of Cite This For Me for Chrome – the browser extension for Google Chrome that allows you to cite APA sources and instantly create and edit a citation for any online web page, without leaving the one you’re viewing.

Cite This For Me gives students the confidence to achieve their full academic potential by encouraging them to research and cite diverse sources. The APA citation generator can help you cite many different kinds of sources; whether it be a PDF report, podcast, a musical score or many more .

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Section 8.17 of the APA Manual, 7 th edition, provides details on the number of authors to be included in in-text citations. As per this section, any work having 3 or more authors will not be written fully. Instead, the Latin words “et al” meaning “and others” have to be used after writing the first author’s name.

Example In-Text Citation Entry for more than 3 authors:

Almost all suppressed persons end up becoming an oppressed person when the same set of situations is presented in their lives (Camus et al., 1975).

In a rare instance, multiple sets of three or more authors might have the same initial pair or initial author. Under such rare situations, Section 8.18 of the APA manual requires you to write out the names of authors in order to distinguish between such confusing references.

Example In-Text Citation Entries:

Bandopadhyay, Schmidt, Wagner et al. (2000)

Bandopadhyay, Schmidt, Meyer et al. (1975)

Section 2.8 of the APA Manual, 7 th edition, provides details on the running head. A shortened version of the paper’s title (50 characters or fewer, including spaces and punctuation), the running head appears on top of each page so that the readers can connect the paper’s content with the title. While running heads are not required for student papers unless explicitly stated by the organization or instructor, manuscripts for publication absolutely require them.

Running heads should be in all-capital letters, flush left (directly across from the page number, which is flush right), and presented in the page header including the title page. You do not need to use the words, “Running head” because it is implied from its presence in the header.

Comparison of Loan Repayment Between Traditional Lending and Online Lending Models (Heading)

COMPARISON OF LOAN REPAYMENT MODELS (Running Head)

Section 2.3 of the APA Manual, 7 th edition provides details on what should appear in a title page for both professionals and students. While students are advised to follow the guidelines from their respective institutions or instructors, the following elements (from top to bottom) are necessary in the absence of any such information.

• Page number at the right hand side top in the header portion (also to be included in all pages)
• Title of the paper in bold, centered and appearing in the middle
• Author’s name
• Affiliation of the author (this will be the university’s name along with the department’s or division’s name)
• Name of the course (format used in the course materials. For example, PSY101)
• Name of the instructor (check with the instructor for their preference of salutation like Dr., Professor, etc.)
• Due date of the assignment with the month spelled out (June 1, 2021, or 1 June, 2021)

Section 2.3 of the APA Manual, 7 th edition provides details on what should appear on a title page for both professional and student papers. The following elements (from top to bottom) are necessary for the professional version of the title page.

• Running head in capitals at the left-hand side of the header portion (included on every page)
• Page number at the right-hand side of the header portion (included on every page)
• Title of the paper in bold, centered, and on the upper portion of the page (usually three or four lines down from the top)
• Authors’ name(s) in full, including first name, middle initial, and last name
• Affiliation of the authors (the university’s or institution’s name where the work referenced in the paper was conducted and the department’s or division’s name)
• Author Note (below the information listed above, this section provides additional pertinent information about authors along with contact information for those interested)

According to section 9.16 of the APA manual, 7th edition, you only need to add “retrieved from” and a retrieval date in a reference entry for web sources designed to be continuously updated. For example, an online reference entry from a dictionary or encyclopedia, or a social media page. Including a retrieval date signals to readers that the source may differ in content if retrieved on a different date. When including the retrieval date, insert it before the URL or DOI at the end of the entry:

Retrieved January 1, 2022, from https://chegg.com

For web sources with stable URLs or DOIs that do not change, do not include a retrieval date. Only include the URL or DOI. Section 9.5 of the APA manual, 7 th edition provides information on how to format DOIs (Digital Object Identifiers) and URLs (Uniform Resource Locators). Both DOIs and URLs are to be presented as hyperlinks (use http:// or https:// as the case may be). Since these are presented as hyperlinks that the readers can use to access the content, it is NOT necessary to have the words, “Retrieved from” or “Accessed from” before a DOI or an URL. However, test the resource to ensure the hyperlink works.

Section 8.11 of the APA Publication Manual , 7 th edition, provides details on parenthetical citations. A parenthetical citation provides the authors’ names and publication date of the source within parentheses along with the cited text. If two authors are present in the source, both authors’ last names should be mentioned in the in-text citation. Their names should be separated by an ampersand (&). The publication date should follow the second surname, separated by a comma.

A parenthetical citation can appear either at the end of the sentence or within the sentence depending on how the sentence is framed. The period or end punctuation appears after the closing parenthesis.

Example parenthetical citation at the end of a sentence:

The reach of fake news is greatly underrated (Rameses & Hudgson, 2021).

If more text appears along with the parenthetical citation, include commas to separate the year and help the reader distinguish the citation from the surrounding text.

Example parenthetical citation with additional text:

The reach of fake news is greatly underrated (see Rameses & Hudgson, 2021, for more detail).

Section 8.11 of the APA Publication Manual , 7 th edition, provides details on narrative citations. A narrative citation provides the authors’ names in running text, and the publication date appears within parentheses immediately after the names. If two authors are present in the source, both authors’ last names should be mentioned in the in-text citation. In narrative citations, the word “and” should be spelled out between the two names.

Example narrative citation with two authors:

Crompton and Williams (2020) noted that gut health is of paramount importance in maintaining mental health.

In some circumstances, the year may also appear within the text along with the authors’ names. In such a scenario, the date should not appear within parentheses.

Example narrative citation with two authors and date:

In 2020, Crompton and Williams broke new ground with their hypothesis that mental health is strongly linked with gut health.

As per Section 2.4 of the APA Publication Manual , 7 th edition, the title of a research paper should summarize the main idea in a succinct manner. While there is no prescribed title length in APA style, authors are advised to keep their titles brief and focused. The manual also provides examples between effective and ineffective titles, including “fluff” words that can be cut from titles and substantive information that should be included in a title to make it relevant to the reader(s).

When the whole book or article is being referenced, there is no need to include a page number. However, when you are referring to a specific page or pages (either in a paraphrase or a direct quote), include the page number(s) in your in-text citation.

If you are referring to information or a quote contained on a single page, add the page number after the author and date, preceded by “p.” If you are citing multiple pages, the page numbers should be preceded by “pp.” and separated by an en-dash.

Example in-text citation with single page number:

(Rayden, 2014, p. 308)

Example in-text citation with page range:

(Rayden, 2014, pp. 308-311)

If there are no page numbers in a work, you can use some other type of locator in in-text citations to help your reader find the information you are citing, like chapter names, headings, or paragraph numbers.

As per Section 8.14 of the APA Publication Manual , 7 th edition, for sources with an unknown author, include the title of the source and year of publication in your in-text citations instead.

If the title of the source is italicized in your reference list, it should also be italicized in your in-text citation. If the title is not in italics in the reference list, it should be in quotation marks in your in-text citation. Titles should be listed in title case (with all important words capitalized) when included in in-text citations.

In-text citation templates:

( Full Name of the Source , year)

(“Full Name of the Source,” year)

In-text citation examples:

( How to Be Awesomely You , 2021)

(“Social Dynamics in US Colleges,” 2018)

If a work’s author is designated as “Anonymous,” use “Anonymous” as the author in in-text citations, as shown below.

(Anonymous, 2020)

As per Section 2.14 of the APA Publication Manual , 7 th edition, an appendix or appendices are included after the references, footnotes, tables, and figures of the paper. In other words, appendices are the last item in your paper. Each appendix should be separately mentioned within the main text (e.g., “see Appendix A”). Appendices are to be self-contained; they should describe the contents and clearly have a label and title.

For a parenthetical in-text citation in APA style, the basic elements needed are the author’s last name (or the group author’s name) and the publication year. For parenthetical citations, format this information by inputting it in parentheses.

For a narrative in-text citation, include the information in the running text. Usually, this means you include the author’s last name followed by the year in parentheses. However, if needed, you may include both the author’s last name and the year in the running text.

For audio, visual, or audiovisual works, replace the author’s last name with a director’s last name (for a film), an uploader’s last name (for YouTube), the artist’s name (for an artwork), and so on.

As per section 2 of the APA 7 manual, papers require the following elements presented in the order below. Since the required elements differ depending on whether your paper is a professional or student paper, there are two lists to distinguish the differences. Sections like Figures, Tables, and Appendices may not be relevant to your paper, so you may exclude those.

Professional Papers*

• Title Page (with title, author(s), affiliations, and an author note)
• Page Headers including a running head and page numbers
• Reference List
• Keywords (optional)
• Footnotes (optional)
• Tables (optional)
• Figures (optional)
• Appendices (optional)
• Supplemental Materials (optional)

*Always refer to the professional journal’s instructions or submission guidelines.

Student Papers

• Page Numbers

An APA reference list comprises the publication details of the studies that specifically quote or support the ideas and concepts presented in a paper. Cite sources in the text, with a narrative or parenthetical citation, and include corresponding reference entries in the reference list.

An APA bibliography is similar to a reference list because it also includes full reference entries for sources cited in the text. However, they also include other sources that support or give background for further research related to the listed source.

An APA annotated bibliography includes short annotations below the reference entry in a separate paragraph(s). Annotations summarize and/or describe a source in detail.

Both the 6 th and 7 th editions of APA style are available on the Cite This For Me citation generator .

For a webpage/website, journal article, or book, you’ll need 1-2 pieces of basic publication information. For example:

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Using unfolding case studies to develop critical thinking for Graduate Entry Nursing students: an educational design research study

• Rachel Macdiarmid   ORCID: orcid.org/0000-0003-4791-7417 1 ,
• Eamon Merrick   ORCID: orcid.org/0000-0003-4269-6360 2 , 3 &
• Rhona Winnington   ORCID: orcid.org/0000-0002-6504-2856 1  

BMC Nursing volume  23 , Article number:  399 ( 2024 ) Cite this article

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Graduate Entry Nursing (GEN) programmes have been introduced as another entry point to nurse registration. In the development of a new GEN programme, a problem-based approach to learning was used to develop critical thinking and clinical reasoning skills of motivated and academically capable students.

To explore and evaluate the design and delivery of course material delivered to GEN students embedded in authentic learning pedagogy from the perspectives of both GEN students and academic staff using an unfolding case study approach.

An educational design research approach was used to explore the learning experiences of GEN students using an unfolding case study approach situated in experiential pedagogy and the teaching experiences of the academics who designed it. Data were collected through semi-structured interviews with students once they had finished the course and weekly reflective diary recordings by academic staff throughout implementation. Thematic analysis was used to analyse the data.

Student reflections highlighted that this cohort had insight into how they learned and were comfortable voicing their needs to academic staff. While the unfolding case studies were not liked by all participants, for some it offered a unique learning opportunity; particularly when scaffolded with podcasts, simulation labs, tutorials and clinical placements. Staff reflections primarily aligned with student experiences.

The gaps highlighted in the delivery of the course suggest that a blended pedagogical approach to graduate entry nurse education is required. Specifically, GEN students are aware of the learning needs and are happy to express these to academic staff, thus suggesting that engaging with a co-design curriculum approach will benefit future cohorts.

Peer Review reports

Graduate entry nursing students begin their degrees as experienced learners and must develop critical thinking skills within the shortened degree time frame.

What is already known

Graduate entry students are experienced and academically capable learners who begin with a diverse range of life and career experiences.

What this paper adds

Graduate entry students would benefit by being involved in curriculum design to acknowledge the unique skill set that they bring.

Introduction

Graduate Entry Nursing (GEN) degrees, or second degrees leading to eligibility for nursing registration, have recently been introduced to New Zealand. GEN students are known to be academically capable, motivated, and driven, bringing with them a range of life experiences, and have often had significant careers before enrolment [ 1 , 2 ]. Previous research has identified that teaching and learning methods must be carefully planned and innovative [ 1 ].

Pre-registration nursing education programmes prepare nursing students to provide safe nursing care with crucial skills expected of nursing graduates, including critical thinking and clinical reasoning. Clinical reasoning enables students to approach clinical issues with a problem-solving lens that relies on gathering assessment data and intervening and evaluating the patient’s response to the intervention [ 3 ].

Problem-Based Learning (PBL) aligns with the fundamental elements of authentic learning approaches [ 4 ], where learning is situated in real-world contexts [ 5 ]. Problem-based learning is considered to be an experiential teaching and learning approach that helps students develop a critical lens and clinical reasoning skills [ 6 , 7 ]. The use of PBL in nursing education is well established with previous research focused on students’ experiences and satisfaction [ 8 ]; factors that facilitate or hinder students' learning [ 9 ]; and the development of critical thinking skills [ 10 ].

Graduate entry nursing students report enjoyment of the active learning sets that enabled discussion surrounding case studies, scenarios, and practice issues [ 11 ]. Cangelosi’s [ 12 ] phenomenological study found that although time-poor, GEN students welcomed learning opportunities that were not traditional and facilitated their development and growth.

However, there is conflicting evidence regarding the effectiveness of PBL in nursing. For example, McCormick et al. [ 13 ] compared undergraduate student performance using differing teaching approaches, such as unfolding simulation scenarios versus recorded lectures and found these to be of benefit to students. Carter and Welch [ 14 ] compared the results of associate degree nursing students who attended lectures to those whose learning was informed by an unfolding case study. In contrast to McCormick’s et al.’s [ 13 ] earlier positive results, these authors found both groups of students performed worse in the post-test.

As previous research has identified that new graduate nurses do not always have critical thinking skills, using an unfolding case study approach can reflect the reality of clinical practice where not all the relevant information is known at the first encounter with the patient [ 14 , 15 , 16 ].

Nonetheless, while several studies have investigated the use of unfolding case studies in undergraduate preregistration programmes there is little evidence that supports the use of these with more academically capable GEN students. This article reports on a qualitative interpretivist study that used an educational design methodology to explore the experiences of GEN students who participated in the programme of learning and the experiences of the academics who designed it.

Educational Design Research (EDR) is an iterative, pragmatic, and reflective methodology well suited to small projects [ 17 ]. It has arisen from design-based research and can include both quantitative and qualitative data collection methods. EDR was selected as it fitted with our desire to develop new ways of teaching alongside gaining feedback from both academic staff and students. In the first phase of this research, we redesigned the teaching and learning strategies for a component of the GEN programme [ 18 ].

EDR has four phases (Table  1 ) [ 17 ]:

Aims and objectives

The study aimed to explore and evaluate the design and delivery of course material delivered to GEN students embedded in authentic learning pedagogy from the perspectives of both GEN students and academic staff using an unfolding case study approach.

Theoretical framework

To enable the development of clinical reasoning skills a scaffolded learning approach was implemented that involved unfolding case studies designed to represent the health needs of the New Zealand population, thus, encouraging critical thinking. Unfolding case studies reflective of situations that students might face in the future were used to encourage students to consider and analyse information, provoke further questioning and identify the information required to narrow their inquiries [ 14 , 15 ]. Supported by this evidence the academic staff built a learning environment where a regular teaching schedule (two days of lectures and one day of clinical labs per week), was complemented with online resources. Initial questions about the case study were provided on the learning management system. Students attended simulations where they responded to the case and answered questions critical to unpacking the ‘patients’ reality. Alongside the unfolding case studies were podcasts where experts were interviewed on topics related to the case. Tutorials enabled students to collaboratively construct answers and share their perspectives; at the end of each week students shared their answers in an online discussion forum.

Methods and setting

This study was conducted at an education facility in New Zealand offering undergraduate and GEN programmes. The participants are academics involved in the design and delivery of the course and one cohort of students of the GEN programme. This article reports on Phase 2 and 3 of the EDR approach, the academic staff’s reflective diary during course delivery, and students' feedback after the course was completed the first time. The methods were reported using the Consolidated Criteria for Reporting Qualitative Studies (COREQ) [ 19 ].

Participants

Purposeful sampling was used as the researchers were keen to explore the experiences of a specific GEN cohort [ 20 ]. Academic staff involved in the weekly reflective diaries are also the research team ( n  = 3). All students in the identified cohort ( n  = 7) were invited to participate, totalling ten possible participants. Student participants were approached via an advertisement on the university’s learning management system. Students were asked to contact the research assistant, who was separate from the academic staff and was not involved in the delivery of the GEN programme; five students agreed to participate. A $20 petrol voucher was offered to those who participated.

Data collection and analysis

In keeping with education design methodology, the authors met weekly to reflect on their experiences of delivering the content and guiding students. The weekly reflective conversations, between 60–90 min in length, followed a simple format of ‘what worked, what didn’t work, and what would we (as academic staff) change?’ Face to face student interviews were conducted by the research assistant at a time and place convenient to the students using semi-structured questions that were developed by the research team (see Additional file 1 ).

The semi-structured interviews ( n  = 5) and reflective meetings ( n  = 9) were recorded and transcribed verbatim by a research assistant who had signed a confidentiality agreement. All identifying information was deleted from the transcripts by the research assistant before the research team reviewed the data; each recording and transcript was allocated a unique identifier, for example ‘participant one’.

Thematic analysis [ 21 , 22 ] was used to analyse the data. First, the research team independently read the transcribed interviews to familiarise themselves with the data and identified initial codes. Second, the researchers met and reviewed all transcripts to identify themes and reached consensus on the themes emerging from the data. Themes were established once more than 50% of the participants stated the same issue/thought/perception. A matrix was developed whereby common themes were identified, with quotes demonstrating the themes collated to establish an audit trail.

Reflexivity

Central to this study given the proximity of staff to this student cohort, a reflexive stance was essential. Reflexivity is an engendered practice and was used in this instance not to influence the direction and outcome of the research but to allow the researchers to engage in the data to produce viable and valuable outcomes for future staff and students. Specifically, this reflexive practice provided a means for the research to be rigorous through the consideration of the vulnerability of the participating student cohort, thus inciting reflection-before-action [ 23 ].

Ethical considerations

Ethical approval for this study was obtained from the Auckland University of Technology Ethics Committee (AUTEC) (19/233). Given the potential power differential in the student/staff relationship present, participants were approached via an online advertisement and followed up by an independent research assistant. This is key to the success of the project, as such research undertakings have the potential for conflict of interest to exist [ 24 ]. The academic staff recordings were also undertaken with the knowledge that these would remain confidential to the participants and transcriber only, with a memorandum of understanding completed to this effect. Participant information sheets were given to students interested in joining the study to ensure they knew what it entailed and how their safety and identity would be managed. Written consent was obtained before the interviews were undertaken, with oral consent obtained at the beginning of each interview.

Three dominant themes emerged, which focused on the experiences of both GEN students and teaching staff. These were:

Reflective learning: Students and staff ability to clarify what worked and what did not work

Evaluation of learning: Students and staff being insightful about their ways of learning and needs

Challenges: Planning and delivering appropriate content for GEN students is challenging for teaching staff.

Within these overarching themes, subthemes were developed and will be presented in the following data results (Table 2 ).

Reflective learning

The exploration of student and staff experiences and responses to the unfolding case studies unearths what worked and what was problematic for both parties.

Unfolding case study as problem-based approach

The student experiences of using an unfolding case study approach were divided. Some students enjoyed the case scenarios but did not necessarily find them beneficial in terms of knowledge advancement as.

“ I personally, like the case studies but personally I didn’t really find that they enhanced my learning in like the clinical setting ” (P1)

or that they were relevant to clinical practice in that.

“… some of it was definitely relatable but I just found it was very different in the clinical setting compared with doing this theoretical case setting ” (P1).

A second student supported this idea that the case studies did not add practical clinical knowledge value as.

“ I mean for me the case studies weren’t challenging…I didn’t think the case studies added anything extra into my practice, they didn’t challenge my clinical reasoning or anything like that ” (P2).

Of note was that those students with previous professional healthcare backgrounds found the use of an unfolding case study approach problematic in that.

“ I found that quite a challenge. I think because with my clinical background I was sort of going straight into, yeah like I wanted more information so you know I probably would have preferred…to have a different case study every week or have all the information…and I’d be like well what about this, what about that? ” (P5).

Participant One, however, noted that while the case studies may not have added knowledge value, they were helpful at times as.

“ …one example is we learnt about arterial blood gases and then I was on placement I came across that literally [on] day one, so was really nice to be able to put something that I’d learnt in class into practice ” (P1).

While some students were less keen on the case study approach and found them hard work, others thought they provided opportunities to encourage discussion, clinical reasoning, and autonomous thinking as.

“ there was no right or wrong answer, you just had to prove your point to say I think it is this because of this, and someone else can say something else and just kind of still prove it because it was a quite grey [area] but I actually found that it really got us thinking ” (P3).

Moreover, the same participant acknowledged that.

“…I think that’s the whole idea of the course [GEN Programme] because at this level they shouldn’t be spoon-feeding you…you should be able to think for yourself and reason things out ” (P3).

Although some discord was present with regard to the case study approach, one participant did acknowledge the value of being able to break down a huge scenario into manageable sections to enhance understanding and clinical decision-making, as.

“ when you break it down it makes it easier to kind of work out what you’re going to do and what steps you’re going to do ” (P4), and that “ because you start looking at the smaller things that you need to do rather than just the big bits ” (P4).

It appears, however, that staff involved in the programme of learning were pleased with the overall notion that problem-based learning approach offered a ‘practical’ means through which to discuss what is the hands-on job of nursing. Specifically,

“ the second session around child abuse and recognising child abuse…took me a bit by surprise as I wasn’t expecting that to go very well and it went extraordinarily well, mostly because it was case based again and story based ” (L1).

Moreover, with regard to encouraging discussion and clinical reasoning at a postgraduate level,

“ I think we’ve really pulled out the difference [of] what we’re expecting of them [GEN students] as opposed to what they may have been used to” (L1).

Use of podcasts

While the use of technology is not necessarily a completely new strategy in tertiary education, here we have linked podcasts recorded with experts in their fields which related to the unfolding case studies, Again, however, there was division in the value of podcast recordings, with some students really enjoying them, saying.

“ I liked the podcasts yeah, I found the podcasts really good especially when there was [sic] different people talking about it, yeah...podcasts are good, like to just chuck on in the car or at the gym ” (P2).

Moreover, some found them easy to listen to because.

“… it’s a different way to learn because like you’ve got YouTube videos and you’ve got books and stuff but podcasts are kind of like easy ” (P2).

Some students found the podcasts particularly engaging saying.

…I just remember listening to it and I think I was in the car and I had stopped because I was on my way home…and I was still listening to it in the garage like when I was home and I was like oh this is a really interesting podcast ” (P2).

Participant three also thought podcasts a positive addition to the resources saying.

“ yeah they were helpful…there was one I listened to…they were talking about dying…I know that [one of the lecturers’] kind of research is kind of talking about death, euthanasia and all this kind of thing, and for some reasons, I don’t know why, maybe that’s why I still remember, I can say it’s the only podcast I really listened to and it was really good because it gave me a good insight as to what is happening… ” (P3)

This positive response was also noted in face-to-face class time as one staff member reported that.

“ they [the students] loved the person who was interviewed, and the feedback was it was really nice to hear a conversation about different perspectives ” (L1).

Yet, not all students were of this opinion, with some advising the podcasts were too long (approximately 60 min each), that they can be distracting, that they preferred videos and images or an in-person discussion, saying.

“ I find podcasts…I tend to switch off a bit, a bit quicker than if I was watching something, I would probably prefer, rather than watching a podcast [sic] I’d rather have an in-class discussion with the person” (P4).

Participant one said that they too struggled with podcasts because.

“ I’m more visual so I like to look at things and see like a slide I guess or what they’re talking about or, so I sort of zone out when it’s just talking and nothing to look at, so that’s what I personally struggle with, they [podcasts] are helpful it’s just I’m more a visual learner ” (P1).

While there were some negative responses to the podcasts, another participant acknowledged their value but offered their own solutions to learning, saying that.

“ I listened to a few podcasts that were put up, because they’re just easy to listen to ” (P2).

but felt that overall there were insufficient resources made available to students and therefore.

“ just went to YouTube and just, any concepts that I was unfamiliar with or stuff in class that we went over and when I went home I was like [I have] no idea what they talked about, I just found my own videos on YouTube… ” (P2).

Evaluation of learning

Learning experiences are unique to each GEN student, as are those experienced by the teaching staff. The data collected highlighted this clearly from both perspectives, offering a particularly strong insight into how this cohort of students’ function.

Approaches to learning

It was evident that these GEN students were aware of their approach to learning and that perhaps the structure of the teaching module did not align with their needs as.

“ I’m not really the best at utilising online things I’m a really hands on learner and things like a lecture…but you know if it’s yeah, more like class time, it’s sort of more my, my learning style [I] guess ” (P5).

A number of students were able to identify that they were visual learners as.

“ I use videos more because I guess I’m more of a visual learner as well and I learn better by seeing things instead of reading a huge article, I think that [videos] it helps me a bit more” (P4).

Another student, however, preferred a discussion based approach as opposed to either videos or podcasts saying that.

“ if it’s interesting, if it’s a topic that you can like relate to [through a podcast] or something it’s fine, but for me I just switch off not really taking a lot of the information [in] whereas in a discussion setting you can ask questions and you can interact with the person, yeah I find that would be a bit more helpful ” (P4).

This approach to learning through discussion was also noted when the teaching staff reflected on their experiences in that in one teaching session the GEN students.

“ were engaged, they were round a table with the second speaker talking and what I think enabled the discussion was that she [the speaker] was using her data as stories and so she was reading them, actually she got them [the students] to read them out” (L3).

The notion of learning styles, however, was not as linear as being visual or auditory or practical, as one student noted that a combination of styles was preferable to enhance learning, saying that.

“ if we weren’t able to have lectures like a recorded lecture so that there was a PowerPoint and just someone actually talking you through it, like I know there’s the YouTube videos…some of them were a little bit helpful, but like I just felt that sometimes we missed the teaching aspect of it. There’s a lot of self-directed stuff but definitely like a recorded lecture every week to go along with the readings and extra videos to watch ” (P5).

Students as insightful and engaged

While GEN students are known for their tenacity and ability to cope with the pressure and fast paced delivery, some students discovered that this did not necessarily equate with their preferred approach to learning. This cohort of GEN students were insightful in terms of their strengths and weaknesses in relation to knowledge acquisition. The use of the unfolding case studies, however, caused some frustrations as.

“ for me it was challenging in the fact that I felt I actually got frustrated because I’m thinking well I want to know this, I want to know that and yeah not getting all the information that I wanted at the time ” (P5).

This participant went further, saying that.

“ I definitely found that difficult [lack of information] I felt like [I] wasn’t getting as much information as I wanted to be able to make my clinical decisions ” (P5),

however this may have been due to the student’s background as their.

“my background is in paramedicine ” where “ we get a lot of information in a very short amount of time ” (P5).

Some fundamental issues were raised by the participants in terms of how much study is required for them to acquire the new knowledge. As one student highlighted,

“ I have a really terrible memory, so I kind of need to listen to things a few times or write it down and then watch a video and do some more reading and then like it’s good having another element to get into your brain you know ” (P2).

For one student, a solution to this was to ensure they did their preparation before attending class as.

“ you’re supposed to have read these things before coming to class, some people don’t but my kind of person, I’d read before coming to class and I tended to answer those questions so the critical, analytical part of me would be trying to find out and come up with a reasonable answer…” (P3).

For another participant, they took an alternative pathway to learning as they.

“ I just watch it and I don’t take [it in], it just sits in the back of my head because sometimes it’s building on top of previous knowledge so just, I just watch it to see if I can gain anything from that, I don’t necessarily take down notes or anything, but I just watch it so that it’s there you know ” (P4).

The pace of content delivery appeared problematic for some students, especially in relation to the practical sessions, with one student highlighting that.

“ personally I didn’t’ really like it and most of the time they were rushing, I was always like can I write this down to go back home to like really make sense of it and then sometimes obviously, sometimes I would have to say can I stay back and practice this thing again [as] I didn’t grab it as quickly as others did and the essence of the labs is that it’s grab all of these things ” (P3).

Challenges: Teaching staff experiences of GEN student learning

While on the whole the teaching staff were able to gauge the learning needs of this GEN cohort, the expectations of both parties did not always align, with one staff member reporting that.

“ the two biggest challenges was [sic] getting them [the students] to unpack already learned behaviour and [to] acknowledge their own limitations or bias ” (L1),

however by the end of the semester the same staff member reported that.

“ I think we made a lot of progress in getting them to acknowledge how they learn ” (L1).

Moreover, the challenges anticipated in teaching GEN students were not those that transpired in that.

“ I actually thought going into the first paper I was pretty excited as to how it was going to roll out, the problems I encountered were not the problems I anticipated ” (L3).

The vocality of this cohort was tangible, however, when content did not meet their needs, interest or expectations with the students saying,

“ that they didn’t do the materials because it wasn’t of interest to them and requested other teaching very much related to the assignment as opposed to anything else …” (L1).

It was expected that the GEN students would be participatory both in class and online irrespective of their ways of learning, but there was a difference in both responses and comfort with this form of engagement. One student that talked about the unfolding case study and the online component of assessment as being problematic said that.

“.. we had to put up about 250 words of something related to the case study every week and then we spoke to someone else, [I] didn’t really like the responses…I didn’t really like having to respond to someone else ” (P3).

Yet in contrast to this statement, the teaching staff were delighted that.

“…actually I got some fantastic questions from one of the students…emailed to me on Monday night about the case that was online for them, questions that I didn’t talk about in [the] lecture, I didn’t introduce the concept…they’re talking about concepts that are currently undergoing international clinical trials” (L1).

This study explored the experiences of both GEN students and academics using unfolding case studies situated in experiential learning pedagogy. The use of unfolding case studies supported with podcasts embraced our idea of developing content situated in real-life contexts. Learning was scaffolded using different teaching approaches such as podcasts, and experiential simulated learning, to offer learners multiple ways of engaging with content. Scaffolding is recognised as learning material being broken into smaller chunks of learning and in this way aligns with case-based learning [ 25 ]. In this way, we hoped that not only would students engage in problem-solving, and develop clinical decision-making skills [ 26 , 27 ], but that they would also achieve deep and lifelong learning and ultimately have an ‘aha’ moment when it all made sense.

Reflections on using an unfolding case study approach

Findings were divided, with some students enjoying the unfolding case studies and others describing them as not sufficiently challenging. The scaffolded learning approach that we developed incorporated a range of teaching approaches that enabled them to engage with the content in a way that fitted in with their lifestyle, even if the teaching method did not align with their individual learning preferences. Students reported differing views about the case studies; some enjoyed the unfolding nature while others wanted more context and direction to feel that they could make an informed clinical decision. Nonetheless, even though they did not like information being presented in smaller chunks one student recognised it meant they analysed the information they received more deeply.

Other learning tools such as podcasts were not always valued by participants and yet, the fact that students were able to provide feedback on their use does indicate that they at least attempted to engage with them.

Student reflections indicate that perhaps the use of unfolding case studies as a learning approach is not the solution to engagement, and that often more traditional teaching methods were preferred Indeed, Hobbs and Robinson’s [ 28 ] study of undergraduate nursing students in the US supported Carter and Welch’s [ 14 ] findings that the use of unfolding case studies were of no direct benefit, whilst Ellis et al.’s., [ 29 ] study confirmed that for final year nurse practitioner students unfolding case studies were beneficial in developing critical thinking and stimulating clinical reasoning. Considering these two conflicting findings, further consideration is needed of how to engage highly motivated GEN students.

As such, our results suggest it can be difficult to predict the needs of the GEN students given the diversity of their previous academic qualifications, career, and often significant life experience they bring to the programme [ 30 , 31 ]. Interestingly students in this study simultaneously demonstrated insight into their needs supporting their previous academic study experience and felt sufficiently secure to voice them, which supports evidence found in D’Antonio et al.’s [ 32 ] study. This suggests that GEN students’ capabilities need to be embraced and incorporated when planning curriculum and scaffolding learning. Anecdotally, we have found that students embrace experiential learning such as that offered in simulation labs whether this involves the use of simulated manikins or not, it seems the hands-on learning offers not only the opportunity to experience simulated reality but also fosters collaboration and problem solving with peers that enables them to dwell in learning of what it is to be a nurse.

Graduate entry students recognised as experienced learners

Our students were not overwhelmingly supportive of the pedagogical approach of unfolding case studies we adopted. As previously recognised GEN students are experienced learners and whilst having differing educational backgrounds bring individual experience and knowledge of their own approach to their learning. Nonetheless, the value of their previous learning experience appears problematic in that those learned behaviours and attitudes need to be refocused to engage with learning how to become a nurse, as demonstrated in the academic staff reflections. Despite this background experience and perceived confidence, some students reflected that online engagement that involved exploring the case studies in discussion forums with colleagues was uncomfortable. This was surprising to the academic staff and contrasted sharply with their reflections on the activity but has been previously noted by Boling et al., [ 33 ].

Implications

Given the disparity that exists between student and academic staff experiences, as demonstrated in our study, co-designing content delivery may offer a progressive solution. By engaging ‘students as partners’ it offers them a much deeper level of involvement in future teaching delivery through collaboration and reciprocation of ideas, thus culminating in appropriate curriculum design [ 34 ]. Collaborating with students in course design might facilitate students learning as they become cognisant of the active engagement of academic staff [ 9 , 10 , 35 ]. In the future, we aim to involve students in any curriculum review and course development to ensure their perspectives influence curriculum design and content delivery.

Even so, our initial intention of scaffolding learning by offering different ways for students to engage with content is supported by recent research by Dong et al. [ 36 ] who found that students performed better academically in a flipped classroom. This point, in association with our findings, suggests that the best approach to content delivery for graduate entry nursing students is to ensure students are involved in curriculum and course design alongside the delivery of learning experiences that are well facilitated and supported by faculty so that students are aware of the expectations, required of them, and importantly how they will be assessed.

Limitations

We acknowledge that the sample size in this study is small in terms of generalisability. However, our findings offer interesting, detailed and in-depth insights into the experiences and needs of both GEN students and the academic staff involved in the development and delivery of educational material. Further work needs to be undertaken to evaluate the experiences of GEN students from a range of educational providers. A longitudinal study has been undertaken to explore the motivations and experiences of GEN students in Australasia [ 37 ], which will also support these findings regarding the learning needs of GEN students.

This study has provided a platform through which academics and GEN students can share their insights of teaching and learning experiences. The results offer a clear insight into what these students expect and need to expedite their learning and how teaching staff must respond. While participants' views were somewhat mixed in relation to the use of unfolding case studies and scaffolded learning these results demonstrate how GEN students are aware of their personal ways of learning and how this translates in terms of education needs. The sharing of these experiences provides an insightful lens through which to re-evaluate pedagogical approaches for GEN students. As such, we suggest that to meet the needs of GEN student’s not only is a blended pedagogical approach appropriate but expanding education design boundaries further through a co-design focused approach to GEN programme design.

Availability for data and materials

The datasets generated and analysed during the current study are not publicly available due privacy and ethical restrictions of the participants, but are available from the corresponding author on reasonable request.

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Macdiarmid, R., Merrick, E. & Winnington, R. Using unfolding case studies to develop critical thinking for Graduate Entry Nursing students: an educational design research study. BMC Nurs 23 , 399 (2024). https://doi.org/10.1186/s12912-024-02076-8

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Title: accelerating complex disease treatment through network medicine and genai: a case study on drug repurposing for breast cancer.

Abstract: The objective of this research is to introduce a network specialized in predicting drugs that can be repurposed by investigating real-world evidence sources, such as clinical trials and biomedical literature. Specifically, it aims to generate drug combination therapies for complex diseases (e.g., cancer, Alzheimer's). We present a multilayered network medicine approach, empowered by a highly configured ChatGPT prompt engineering system, which is constructed on the fly to extract drug mentions in clinical trials. Additionally, we introduce a novel algorithm that connects real-world evidence with disease-specific signaling pathways (e.g., KEGG database). This sheds light on the repurposability of drugs if they are found to bind with one or more protein constituents of a signaling pathway. To demonstrate, we instantiated the framework for breast cancer and found that, out of 46 breast cancer signaling pathways, the framework identified 38 pathways that were covered by at least two drugs. This evidence signals the potential for combining those drugs. Specifically, the most covered signaling pathway, ID hsa:2064, was covered by 108 drugs, some of which can be combined. Conversely, the signaling pathway ID hsa:1499 was covered by only two drugs, indicating a significant gap for further research. Our network medicine framework, empowered by GenAI, shows promise in identifying drug combinations with a high degree of specificity, knowing the exact signaling pathways and proteins that serve as targets. It is noteworthy that ChatGPT successfully accelerated the process of identifying drug mentions in clinical trials, though further investigations are required to determine the relationships among the drug mentions.

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Advancing drug-response prediction using multi-modal and -omics machine learning integration (MOMLIN): a case study on breast cancer clinical data

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Md Mamunur Rashid, Kumar Selvarajoo, Advancing drug-response prediction using multi-modal and -omics machine learning integration (MOMLIN): a case study on breast cancer clinical data, Briefings in Bioinformatics , Volume 25, Issue 4, July 2024, bbae300, https://doi.org/10.1093/bib/bbae300

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The inherent heterogeneity of cancer contributes to highly variable responses to any anticancer treatments. This underscores the need to first identify precise biomarkers through complex multi-omics datasets that are now available. Although much research has focused on this aspect, identifying biomarkers associated with distinct drug responders still remains a major challenge. Here, we develop MOMLIN, a multi-modal and -omics machine learning integration framework, to enhance drug-response prediction. MOMLIN jointly utilizes sparse correlation algorithms and class–specific feature selection algorithms, which identifies multi-modal and -omics–associated interpretable components. MOMLIN was applied to 147 patients’ breast cancer datasets (clinical, mutation, gene expression, tumor microenvironment cells and molecular pathways) to analyze drug-response class predictions for non-responders and variable responders. Notably, MOMLIN achieves an average AUC of 0.989, which is at least 10% greater when compared with current state-of-the-art (data integration analysis for biomarker discovery using latent components, multi-omics factor analysis, sparse canonical correlation analysis). Moreover, MOMLIN not only detects known individual biomarkers such as genes at mutation/expression level, most importantly, it correlates multi-modal and -omics network biomarkers for each response class. For example, an interaction between ER-negative-HMCN1-COL5A1 mutations-FBXO2-CSF3R expression-CD8 emerge as a multimodal biomarker for responders, potentially affecting antimicrobial peptides and FLT3 signaling pathways. In contrast, for resistance cases, a distinct combination of lymph node-TP53 mutation-PON3-ENSG00000261116 lncRNA expression-HLA-E-T-cell exclusions emerged as multimodal biomarkers, possibly impacting neurotransmitter release cycle pathway. MOMLIN, therefore, is expected advance precision medicine, such as to detect context–specific multi-omics network biomarkers and better predict drug-response classifications.

The advent of high-throughput sequencing technologies has revolutionized our ability to collect various ‘omics’ data types, such as deoxyribonucleic acid (DNA) methylations, ribonucleic acid (RNA) expressions, proteomics, metabolomics and bioimaging datasets, from the same samples or patients with unprecedented details [ 1 ]. By far, most studies have performed single omics analytics, which capture only a fraction of biological complexity. The integration of these multiple omics datasets offers a more comprehensive understanding of the underlying complex biological processes than single-omic analyses, particularly in human diseases like cancer and cardiovascular disease, where it significantly enhances prediction of clinical outcomes [ 2 , 3 ].

Cancer is a highly complex and deadly disease if left unchecked, and its heterogeneity poses significant challenges for treatment [ 4 ]. Standard treatments, including chemotherapy with or without targeted therapies, aim to reduce tumor burden and improve patient outcomes such as survival rate and quality of life [ 5–7 ]. However, even for the most advanced therapies, such as immunotherapies, treatment effectiveness varies widely across cancer types and even between patients with same diagnosis [ 8 ]. This heterogeneity is believed to be due to tumor microenvironment heterogeneity and their effects on the resultant complex and myriad molecular interactions within cells and tissues [ 9 , 10 ]. This variability underscores the urgent need to identify precise biomarkers to predict individual patient responses and potential adverse reactions to a particular therapy [ 11 ]. This can be made possible through multi-omics data integration analyses at the individual patient scale [ 12 ].

To assess treatment response, such as pathologic complete response (pCR) and residual cancer burden (RCB), current clinical practice relies on clinical parameters (e.g. tumor size/volume and hormone receptor status), along with genetic biomarkers (e.g. TP53 mutations) [ 13–15 ]. However, these approaches do not fully capture the complex intracellular regulatory dynamics [ 16 , 17 ] or the tumor-immune microenvironment (TiME) interactions that influence outcomes [ 18 , 19 ]. Thus, to enhance personalized cancer treatments, we need novel methodologies that can handle large, complex molecular (omics) and clinical datasets. Machine learning (ML) methods integrating multi-omics data offer a promising avenue to improve prediction accuracy and uncover robust biomarkers across drug-response classes [ 20 ], which may be overlooked by single-omics analytics. This approach can predict patients benefiting from standard treatments and those requiring alternative plans like combination therapies or clinical trials.

The current drug-response prediction methods can be broadly categorized into ML-based and network-based approaches. ML methods often analyze each data type (e.g. mutations and gene expression) independently using univariable selection [ 21 , 22 ] or dimension reduction methods [ 23 ]. These results are then integrated using various classifiers or regressors [e.g. support vector machine, elastic-net regressor, logistic regression (LR) and random forest (RF)] [ 24–26 ] and ensemble classifier to make predictions [ 9 ]. However, these methods often overlooked the crucial interactions among different data modalities. Deep learning methods, while gaining popularity, are limited by the need for large clinical sample sizes to achieve sufficient accuracy [ 27 ]. Recent ML advancements have focused on integrating multimodal omics features with patient phenotypes to improve predictive performance [ 28 , 29 ]. To discover multimodal biomarker, techniques such as multi-omics factor analysis (MOFA) and sparse canonical correlation analysis (SCCA), including its variant multiset SCCA (SMCCA) offer realistic strategies for integrating diverse data modalities [ 30–32 ]. However, although these methods are suitable for classification tasks, they are unsupervised and do not directly incorporate phenotypic information (e.g. disease status) to integrate diverse data types. As a result, they are limited to identify phenotype-specific biomarkers.

Recently, advanced supervised approaches like data integration analysis for biomarker discovery using latent components (DIABLO) by Sing et al. (2019) have emerged to overcome these limitations [ 28 ]. DIABLO is an extension of generalized SCCA (GSCCA), considers cross-modality relationships and extracts a set of common factors associated with different response categories. Network-based methods, like unsupervised network fusion or random walk with restart approaches construct drug–target interaction and sample similarity networks that are effective for patient stratification [ 20 , 33 ]. However, these methods lack a specific feature selection design, limiting their utility for identifying biomarkers for patient classification. Nevertheless, none of these ML methods are rigorous in terms of task/class-specific biomarker discovery and interpretability, and both SMCCA and GSCCA struggle with gradient dominance problem due to naive data fusion strategies [ 34 ]. Therefore, it is essential to develop novel interpretable methods for identifying robust multimodal network biomarkers across diverse data types to advance our understanding of the complex factors that influence drug responses.

In this study, we introduce MOMLIN, a multi-modal and -omics ML integration framework to enhance the prediction of anticancer drug responses. MOMLIN integrates weighted multi-class SCCA (WMSCCA) that identifies interpretable components and enables effective feature selection across multi-modal and -omics datasets. Our method contributes in three keyways: (i) innovates a class-specific feature selection strategy with SCCA methods for associating multimodal biomarkers, (ii) includes an adaptive weighting scheme into multiple pairwise SCCA models to balance the influence of different data modalities, preventing dominance during training process and (iii) ensures robust feature selection by employing a combined constraint mechanism that integrate lasso and GraphNet constraints to select both the individual features and subset of co-expressed features, thereby preventing overfitting to high-dimensional data.

We applied MOMLIN to a multimodal breast cancer (BC) dataset of 147 patients comprising clinical features, DNA mutation, RNA expression, tumor microenvironment and molecular pathway data [ 9 ], to predict drug-response classes, specifically distinguishing responders and non-responders. Our results demonstrate MOMLIN’s superiority in terms of outperforming state-of-the-art methods and interpretability of the underlying biological mechanisms driving these distinct response classes.

Overview of our proposed method for treatment response prediction

The workflow of our proposed method MOMLIN for identifying class- or task-specific biomarkers from multimodal data is shown in Fig. 1 . The core of this pipeline involves three stages: (i) identification of response-specific sparse components, in terms of input features and patients, (ii) development of drug-response predictor using latent components of patients and (iii) interpretation of sparse components and multi-modal and -omics biomarker discovery.

Schematic representation of the proposed framework. In stage 1, multimodal datasets from cancer patients (e.g. BC) were sourced from a published study [ 9 ]. This dataset comprises clinical features, DNA mutations, and gene expression from pre-treatment tumors, alongside post-treatment response classes (pCR, RCB-I to III). TiME and pathway activity were derived from transcriptomic data using statistical algorithms. For identifying class-specific correlated biomarkers, class binarization and oversampling were used to balance between classes. WMSCCA models the multimodal associations across different biomarkers and identifies response-specific sparse components on diverse input features and patients. In stage 2, a binary LR classifier then utilizes these patient latent components for predicting response to therapies, evaluated by AUROC. Next in stage 3, class–specific sparse components are shown in a heatmap, highlighting key signatures (non-zero loading) in colors. Finally, the identified multi-modal and -omics signatures then formed a correlation network, revealing pathways associations with multi-modal and -omics biomarkers for each response class. Nodes with colors in the network indicate multimodal features.

The rationales underpinned of this approach is that effective biomarkers are: (i) response–related multimodal features including genes, cell types and pathways, and (ii) features that demonstrate prediction capabilities on unseen patients. The first stage, a ‘feature selection step’ that selects multimodal features on the generated sparse components based on their relevance to drug-response categories (pCR and RCB-I to III). Features with high loading identified are considered as potential biomarker candidates. The second stage, a ‘classification step’, validates these biomarkers by assessing their predictive power in distinguishing responders from non-responders to anticancer therapy; any predictions indicating chemo-resistant tumors should be considered for enrolment in clinical trials for novel therapies. The third stage, an ‘interpretation step,’ analyzes the candidate biomarkers in a multi-modal and-omics network associated with relevant biological pathways. This step aims to elucidate the underlying biological processes differentiating between drug–response phenotypes.

Stage 1. Identification of response-associated sparse components in terms of input features and patients

Multi-modal and -omics data overview and preparation.

This study utilized clinical attributes, DNA mutation and gene expression (transcriptome) data from147 matched samples of early and locally advanced BC patients (categorized as pCR, n  = 38, RCB-I, n  = 23, or RCB-II, n  = 61, or RCB-III, n  = 25), obtained from the TransNEO cohort at Cambridge University Hospitals NHS Foundation [ 9 ]. The dataset includes clinical attributes (8 features, summary attributes are available in Supplementary Table S1 available online at http://bib.oxfordjournals.org/ ), genomic features (31 DNA mutation genes, applying a strict criterion of genes mutated in at least 10 patients) and RNA-sequencing (RNA-Seq) features (18 393 genes), covering major BC subtypes-normal-like, basal-like, Her2, luminalA and luminalB. Although DNA mutation genes typically represent binary data, we used mutation frequencies to construct a mutation count matrix. Initial data pre-processing involved a log2 transformation on the RNA-Seq features after filtering out less informative features at 25th percentile (in terms of mean and standard deviation) using interquartile range. For integrative modeling, we used the top 40% of variable genes (3748 genes, based on median absolute deviation ranking) from the RNA-Seq datasets. Finally, each feature was normalized dividing by its Frobenius norm, adjusting the offset between high and low intensities across different data modalities.

To characterize TiME and pathway markers, we applied various statistical algorithms on the RNA-Seq data. The GSVA algorithm [ 35 ] calculated (i) the GGI gene sets [ 36 ] and (ii) STAT1 immune signature scores [ 37 ]. For immune cell enrichment, three methods were used: (i) MCPcounter [ 37 ] with voom-normalized RNA-Seq counts; (ii) enrichment over 14 cell types using 60 gene markers, employing log2-transformed geometric mean of transcript per million (TPM) expression [ 38 ]; and (iii) z -score scaling of cancer immunity parameters [ 39 ] to classify four immune processes (major histocompatibility complex molecules, immunomodulators, effector cells and suppressor cells). Additionally, the TIDE algorithm [ 40 ] computed T-cell dysfunction and exclusion metrics for each tumor sample using log2-transformed TPM matrix of counts, which can serve as a surrogate biomarker to predict the response to immune checkpoint blockade. Pathway activity scores for each tumor sample were computed using the GSVA algorithm with input gene sets from Reactome [ 41 ], PIP [ 42 ] and BioCarta databases within the MSigDB C2 pathway database [ 43 ].

Sparse multiset canonical correlation analysis

In this study, lowercase letters denote a vector, and uppercase ones denote matrices, respectively. The term |${\left\Vert .\right\Vert}_{1,1}$| denotes the matrix |${l}_1$| -norm, and |${\left\Vert .\right\Vert}_{gn}$| denotes the GraphNet regularization. The sparse multiset canonical correlation analysis (SMCCA) is an extension of dual-view SCCA, proposed to model associations among multiple types of datasets [ 31 ]. Given the multiple types of datasets, let |$X\in{\mathcal{R}}^{n\times p}$| represent gene expression data with |$p$| features, and |${Y}_k\in{\mathcal{R}}^{n\times{q}_k}$| represent the |$k$| -th data modality (e.g. clinical, DNA mutation and tumors microenvironment) with |${q}_k$| features. Both |$X$| and |${Y}_k$| have |$n$| samples, and |$k=\left(1,\dots, K\right)$|⁠ , where |$K$| denotes the number of different data modalities. The objective function of SMCCA is defined as follows:

where |$u$| and |${v}_k$| are the canonical weight vectors corresponding to |$X$| and |${Y}_k$|⁠ , indicating the importance of each respective biomarkers. The term |${\left\Vert .\right\Vert}_1$| represents the |${l}_1$| regularization to detect small subset of discriminative biomarkers and prevent model overfitting. |${\lambda}_u,{\lambda}_{vk}$| are non-negative tuning parameters balancing between the loss function and regularization terms. The term |${\left\Vert .\right\Vert}_2^2$| denotes the squared Euclidean norm to constraint weight vectors |$u$| and as unit length |${v}_k$|⁠ , respectively.

However, SMCCA has limitations: (i) it is naturally unsupervised, meaning SMCCA cannot leverage phenotypic information (e.g. disease status and drug-response classes); (ii) pairwise association among multiple data types can vary significantly and can lead to gradient dominance issues during optimization; and (iii) SMCCA mines a common subset of biomarkers for classifying different tasks, which diminishes its relevance, as each task might require distinct features sets.

Weighted multi-class sparse canonical correlation analysis

To address the above limitations, here we propose weighted multi-class SCCA (WMSCCA), a formal model for class/tasks-specific feature selection, different from the conventional SMCCA. Throughout this study, we used the terms tasks/classes/drug-response classes interchangeably. WMSCCA includes phenotypic information as an additional data type, employs a weighting scheme to resolve the gradient dominance issue and innovates traditional class–specific feature selection strategies through the one-versus-all strategies into its core objective function. In this study, the underlying motivation is WMSCCA can jointly identify drug-response class–specific multimodal biomarkers to improve drug-response prediction. For ease of presentation, we consider |$n$| patients with data matrices |${X}_c\in{\mathcal{R}}^{n\times p},{Y}_{ck}\in{\mathcal{R}}^{n\times{q}_k}$|⁠ , and |$Z\in{\mathcal{R}}^{n\times C}$| from C different drug-response classes. Here, |${X}_c$| denotes |$p$| features from gene expression datasets, |${Y}_{ck}$| denotes |${q}_k$| features from |$k$| -th data modality (e.g. mutation, clinical features, TiME and pathway activity), |${Z}_c$| denotes |$c$| response class, and |$k=\left(1,\dots, K\right)$|⁠ , |$K$| denotes the number of data modalities. The WMSCCA optimization problem can be formulated as follows:

where |$U\in{\mathcal{R}}^{p\times C},{V}_k\in{\mathcal{R}}^{q_k\times C}$| are canonical loading matrices correspond to |$X$| and |${Y}_k$|⁠ , representing the importance of candidate biomarkers for each class |$C$|⁠ , respectively. In this equation, the first term models associations among |$X$|⁠ , and |${Y}_k$| datasets; the second- and third terms correlate class labels |${Z}_c$| with |$X$| and |${Y}_k$| data modalities for each |${C}^{th}$| class, aiming to identify class-specific features and their relationships; |$\psi (U)$| and |$\psi \left({V}_k\right)$| represent sparsity constraints on |$U$| and |${V}_k$|⁠ , to select a subset of discriminative feature. As mentioned in Equation ( 1 ), to address gradient dominance, the adjusting weight parameter |${\sigma}_{xy}$|⁠ , |${\sigma}_{xz}$| and |${\sigma}_{yz}$| can be defined as:

where |$k=\left(1,\dots, K\right)$|⁠ , |$K$| denotes the number of data modalities. |${\sigma}_{..}$| adjusts a larger weight if the non-squared loss (denominator term) between datasets is small and vice versa.

Given high-dimensional datasets, the model in Equation ( 2 ) encounters an overfitting problem. Therefore, the use of a sparsity constraint is appropriate to address this issue. We hypothesized that gene expression biomarkers can be either single genes or co-expressed sets; thus, a combined penalty is designed for the |$X$| dataset. Therefore, |$\psi (U)$| for |$X$| takes the following form:

where, |${\mathrm{\alpha}}_u,\beta$| are nonnegative tuning parameters. |$\beta$| balances between the effect of co-expressed and individual feature selection. The first sparsity constraint is matrix |${l}_{1,1}$| -norm, which is defined as follows:

This penalty promotes class-specific features on |$U$|⁠ . The second sparsity constraint GraphNet regularization, defined as follows:

where |${L}_c$| represents the Laplacian matrices of the connectivity in |$\boldsymbol{X}$| matrices. The Laplacian matrix is defined as |$L=D-A$|⁠ , where |$D$| is the degree matrix of connectivity matrix |$A$| (e.g. gene co-expression or correlation network). This penalty term promotes a subset of connected features to discriminate each response on |$U$|⁠ .

Besides, neither every mutation marker nor every clinical/TiME/pathways involves in predicting response classes, therefore, the |${l}_{1,1}$| -norm is used on the |${Y}_k$| datasets to select individual markers, i.e. |$\psi \left({V}_k\right)$| for the |${\boldsymbol{Y}}_k$| data modalities take the following form:

where |${\mathrm{\alpha}}_{vk}$| is non-negative tuning parameter.

Finally, we obtained C pairs of canonical weight matrices |$\big({U}_c{V}_{ck}\big)\left(c=1,\dots, C;k=1,\dots, K\right)$| using an iterative alternative algorithm by solving Equation ( 2 ) [ 44 , 45 ]. Detected features with non-zero weights in each class in the weight vectors were extracted as correlated sets.

The WMSCCA method involves parameters |${\mathrm{\alpha}}_u,\mathrm{\beta}, and\ {\mathrm{\alpha}}_{vk}$| |$\left(k=1, \dots, K\right)$|⁠ . Given the limited number of samples, we applied a nested cross-validation (CV) strategy on training sets and evaluated the maximum correlation on the test datasets. Optimal values for the regularization parameters were determined within each training set via internal five-fold CV.

Stage 2. Drug-response prediction using latent components of patients

To predict drug-response categories, we trained LR classifier using the latent components of patients (or raw multimodal features) generated by MOMLIN in Fig. 1 : stages 1 and 2. We used a binary classification scheme, distinguishing pCR versus non-pCR, RCB-I versus non-RCB-I, RCB-II versus non-RCB-II and RCB-III versus non-RCB-III, to evaluate model performance. In addition, we performed analyses with existing multi-omics methods, including SMCCA+LR, MOFA+LR, DIABLO and latent principal component analysis (PCA) features, with LR classifiers. To assess prediction performance for the response to treatment in an unbiased manner, we used five-fold cross-validated performance and repeated the process over 100 runs. The partitioning of data was kept consistent across all models for fair comparisons. The accuracy of response prediction was evaluated using area under the receiver operating characteristic curve (AUROC).

Stage 3. Interpretation of sparse components and multi-omics biomarker discovery and their networks

After learning sparse latent components of features across different data modalities using MOMLIN, we identify the most relevant feature based on the loading weight of genes, TiME and pathways, which reveal underlying interactions for discriminating response classes. The larger the loading weight, the more important the pair of features in discriminating response categories. We then use these selected features to construct a sample correlation network, or a relationship matrix based on their canonical weights [ 46 ]. In this network, nodes represent selected features, and the edge weights between two interconnected features indicate correlation or relatedness. The generated network is visualized using the ggraph package in R ( https://cran.r-project.org ). Finally, we prioritize multi-omics biomarkers based on their degree centrality within the interconnected correlation network.

Derivation of response-associated latent components from BC data with MOMLIN

We applied MOMLIN to analyze a breast cancer (BC) dataset to predict treatment response and gain molecular insights. The dataset comprised 147 BC patients with early and locally advanced pretherapy tumors [ 9 ], categorized as follows: pCR with 38 patients, RCB-I (good response) with 23 patients, RCB-II (moderate response) with 61 patients and RCB-III (resistance) with 25 patients. After preprocessing and filtering least informative features, the final dataset comprised 3748 RNA genes (top 40% out of 9371 genes), 31 mutation genes, 8 clinical attributes, 64 TiME and 178 pathways activities ( Fig. 1 : stage 1). Supplementary Table S1 available online at http://bib.oxfordjournals.org/ summarizes overall clinical characteristics by patients’ response classes.

While our proposed framework offers general applicability for identifying context-specific multi-omics biomarkers, this study specifically focused on discovering drug-response–specific biomarkers to enhance the prediction of pCR and RCB resistance. MOMLIN decomposed the input multimodal data into response-associated sparse latent components of input-features and patients. These sparse components reveal patterns of how various features (e.g. genes and mutations) and clinical attributes related to treatment outcomes ( Fig. 1 : stage 1–3), and their effectiveness was evaluated by measuring prediction performance. We assessed the predictive ability of MOMLIN through five-fold CV repeated 100 times. In each iteration, the dataset is divided into five-folds, with one random fold assigned as the held-out test set, and the remaining folds used as the training set. MOMLIN was trained using the training dataset, including detection of predictive marker candidates, and its performance was evaluated on the ‘unseen’ test set. This process was repeated for all five-folds to ensure robust evaluation of MOMLIN’s generalizability. Performance was measured by the AUROC matrices ( Fig. 1 : stage 2).

Performance comparison with existing methods for drug-response prediction

To evaluate the prediction capability of MOMLIN, we modeled each response category as a binary classification problem and compared its prediction accuracy to existing multi-omics integration algorithms. For comparison, we randomly split the dataset into a training set (70%) and a test set (30% unseen data), with balanced inclusion of response classes. We employed LR as the classifier to assess predictive performance of multimodal biomarkers. We compared MOMLIN with four other classification algorithms for omics data: (i) SMCCA, which integrates multi-omics data by projecting it onto latent components for discriminant analysis; (ii) MOFA, which decomposes multi-omics data into common factors for discriminant analysis; (iii) sparse PCA; and (iv) DIABLO, a supervised integrative analysis method, represent the state-of-the-art in classification. All methods were trained on the same preprocessed data.

The classification results showed that MOMLIN outperformed the compared multi-omics integration methods in most classification tasks on unseen test samples ( Fig. 2A ). Notably, DIABLO, the next best performer, was 10 to 15% less effective than our MOMLIN. Additionally, we compared the performance of component-based LR models against raw feature-based LR models to predict RCB response classes. Although raw feature-based models showed improved prediction, their performance was notably dropped compared to component-based models ( Fig. 2B ). This indicates the superior adaptability and effectiveness of component-based models in leveraging multi-omics data for predictive purposes.

Performance comparison with existing methods and detection of informative data combination. All results in the plots depict test AUROC over five-fold CV obtained from 100 runs. (A) Box plots comparing response prediction performance of MOMLIN against existing state-of-the-art multi-omics methods. (B) Performance comparison between predictors based on latent components and those utilizing a selected subset of multimodal features. (C) Comparing AUROCs for the models with different data subset combinations (clinical, clinical + DNA, clinical + RNA and clinical + DNA + RNA) using MOMLIN.

Moreover, to test and demonstrate generalizability of this framework, we applied MOMLIN to a preprocessed multi-omics dataset of colorectal adenocarcinoma (COAD) with 256 patients [ 47 ]. This dataset included gene expression, copy number variations and micro-RNA expression data, which we used to classify COAD subtypes such as chromosomal instability (CIN, n  = 174), genomically stable (GS, n  = 34) and microsatellite instability (MSI, n  = 48). The performance results shown in Supplementary Table S2 available online at http://bib.oxfordjournals.org/ and Supplementary Figure S1 available online at http://bib.oxfordjournals.org/ , indicate that MOMLIN outperformed all state-of-the-art methods tested in classifying COAD subtypes. Moreover, when comparing the raw feature-based accuracies with sparse components-based (features derived from MOMLIN) accuracies, we found that raw feature-based classifier was superior against existing methods ( Figure S1A and B ), but lower than the components-based classifier. This consistent observation supports our findings with BC drug-response performances.

Importance of different omics data for treatment response prediction

To assess the added value of integrating multimodal data for predicting treatment response, we trained four prediction models with different feature combinations: (i) clinical features only, plus adding (ii) DNA, (iii) RNA and (iv) both DNA and RNA. We found that adding different data modalities improved prediction performance across all response classes ( Fig. 2C ). Notably, the models that combined clinical data with either RNA or both DNA and RNA demonstrated superior and comparable performance with an average AUROC of 0.978. In contrast, the model based on clinical features alone had much lower AUROC, ranging from 0.51 to 0.82. These results suggest that RNA transcriptome is the most informative data modality in this dataset. Thus, integrating gene expression with clinical features could significantly improve our ability to predict treatment outcomes in BC.

Interpretation of response-associated sparse components identified by MOMLIN

To understand the molecular landscape of treatment response in BC, we used MOMLIN to model response–specific bi-multivariate associations across multiple data modalities. We observed stronger correlations between RNA gene expression and both TiME ( r  = 0.701) and pathway activity ( r  = 0.868), indicating greater overlap or explained information between them. Conversely, moderate correlations were found between RNA gene expression and DNA mutations ( r  = 0.526), or clinical features ( r  = 0.488), indicating partially overlapping or independent information. These results suggest that multimodal biological features provide complementary information in a combinatorial manner.

When investigating the importance of each feature to predict response classes, MOMLIN identified four distinct loading vectors corresponding to pCR and RCB response classes, highlighting distinct weight patterns for pCR versus non-pCR and RCB versus non-RCB classes ( Fig. 3 ). For example, in the pCR (complete response) components—taking the top five molecular features across different modalities revealed distinct molecular patterns. Specifically, gene expression analysis showed that downregulation of FBXO2 and RPS28P7 inhibits tumor cell proliferation, and potentially may enhance treatment efficacy, and the upregulation of C2CD4D-AS1, CSF3R, and SMPDL3B genes may promote immune response, increasing tumor cell vulnerability and therapeutic effect ( Fig. 3A ). Mutational analysis revealed negative associations of marker genes HMCN1 and GATA3, but a positive association for COL5A1 ( Fig. 3C ). Additionally, tumor mutation burden (TMB), and homologous recombination deficiency (HRD)-Telomeric AI signatures were higher in pCR patients, suggesting high genomic instability compared to RCB patients [ 9 ]. TiME analysis showed reduced immunosuppressive mast cells and extracellular matrix (ECM), along with increased infiltration of neutrophils, TIM-3 and CD8+ T-cells ( Fig. 3D ). Subsequently, the pathway analysis further revealed potential downregulation of the PDGFRB pathway, involved in stromal cell activity and associated with improved patient response [ 49 ], while upregulation of pathways for antimicrobial peptides, FLT3 signaling, ephrin B reverse signaling and potential therapeutics for SARS ( Fig. 3E ), suggesting enhanced immune surveillance and interaction with tumor cells. In summary, MOMLIN reveals distinct genomic landscape with higher immune activity and genomic instability in pCR that characterizes its favorable treatment response.

Heatmaps illustrate the features importance on response-associated components identified by MOMLIN. Each row in the heatmap represents a drug-response class, pCR, RCB-I , RCB-II and RCB-III, with columns representing features across different data modalities. The color gradient indicates feature loading or importance, representing the strength of association with response classes. The sign (negative or positive) of gradient denotes the association directions to response classes. All results in the heatmaps depict an average over 100 runs of five-fold CV. (A–E) represents the response-associated candidate biomarkers detected in latent components in (A) gene expression data (highlighting DE genes), (B) clinical features, (C) DNA mutations (highlighting mutated genes), (D) TiME cells and (E) functional pathway profiles (highlighting altered pathways).

Similarly, in the RCB-I (good response) components—RNA expression analysis revealed that lower expression of genes GPX1P1 and HBB are linked to less aggressive tumors [ 48 ], while those of thiosulfate sulfurtransferase (TST), NPIPA5 and GSDMB were overexpressed, linked to enhanced immune response and therapeutic effectiveness [ 49 , 50 ]. Mutational analysis showed positive association for therapeutic targets signatures TP53, MUC16 and RYR2 [ 51 , 52 ], but a negative in NEB, and CIN scores. TiME analysis demonstrated increased infiltration of Tregs, cancer-associated fibroblast (CAF), monocytic lineage and natural killer (NK) cells, indicating more active of immune environment [ 9 ], with reduced TEM CD4 cells. Pathway analysis further identified downregulation of NOD1/2 signaling, EPHA-mediated growth cone collapse and toll-like receptor (TLR1, TLR2) pathways, involved in inflammation and immune response, with the upregulation of allograft rejection, and G0 and early G1 pathways. In summary, tumors that achieve RCB-I is marked by distinct genomics marker, active immune response, and lower CIN.

In RCB-II (moderate response) components: RNA expression analysis revealed overexpression of RPLP0P9, FTH1P20, RNF5P1 pseudogenes, following accumulation of overexpressed ERVMER34-1, and PON3 genes play an oncogenic role in BC [ 53 ]. Mutation analysis revealed positive association of HRD-LOH, RYR1 and MT-ND4, but negative association of MACF1 and neoantigen loads, in line with previous reports [ 54 , 55 ]. Analysis of TiME features demonstrated increased infiltration of IDO1 and TAP2, with reduced CTLA 4, NK cells and PD-L2 cells, indicating a less suppressive immune environment. Pathways analysis further revealed downregulation pathways of G1/S DNA damage checkpoints and TP53 regulation, highlighting DNA repair issues, with the upregulation of PDGFRB pathway, E2F targets and signaling by Hedgehog associated with cell proliferation. In summary, RCB-II patients display distinct genomics markers including pseudogenes, lack of suppressive immune environment and active proliferation.

In RCB-III (resistant) components: RNA gene expression analysis revealed lower expression of therapeutic target PON3, and FGFR4 [ 56 ], and flowed accumulation of lower expressed lncRNAc ENSG00000225489, ENSG00000261116 and RNF5P1. Mutation signature analysis identified a positive association of MT-ND1, but a negative association in therapeutic targets TP53, and MT-ND4 [ 7 , 52 ]. Neoantigen loads were higher following lower TMB indicate reduced tumor suppressor activity. TiME analysis revealed reduced activity of T-cell exclusion, and HLA-E, with increased ECM, HLA DPA1 and LAG3, suggesting an immune suppressive tumor environment. Pathway analysis revealed upregulation of pathways involved in neurotransmitter release, cell-cycle progression (RB-1) and immune system diseases, suggesting active cell signaling and proliferation, with downregulation of EPHB FWD pathway and nucleotide catabolism. In summary, patients that attained RCB-III, characterized by low mutational burden and an immune suppressive environment, leading to treatment resistance.

Linking biology to treatment response through biomarker network analysis

To further extract multimodal network biomarkers and understand the complex biological interactions in patients with pCR and RCB, we performed cross-interaction network analysis using candidate signatures identified by MOMLIN across different modalities. This analysis included clinical features, DNA mutations, gene expression, TiME cells and enriched pathways, aiming to elucidate the underlying biology associated with specific treatment responses. Figure 4 shows the interaction networks of selected multimodal features for each RCB class. To identify potential biomarkers associated with pCR and RCB response, we specifically focused on the top ten multimodal features based on network edge connections. For example, tumors that attained in pCR, the network analysis revealed co-enrichment of mutations in HMCN1 and COL5A1 genes, particularly in estrogen receptor (ER)-negative patients. HMCN1 and COL5A1 therapeutic targets like molecules encode proteins for ECM structure, and mutations of these genes regulate tumor architecture and cell adhesion, potentially facilitating immune cell infiltration [ 52 ]. We also observed elevated expressions of FBXO2, CSF3R, C2CD4D-AS1 and RPS28P7 genes, alongside increased infiltration of CD8+ T-cells [ 9 , 57 ]. FBXO2 is a component of the ubiquitin-proteasome system, which regulates protein degradation and influences cell cycle and apoptosis [ 58 ], while CSF3R plays a vital role in granulocyte production and immune response [ 59 ]. These gene expression patterns, coupled with increased CD8+ T-cell infiltration, suggest a robust anti-tumor immune response. Furthermore, these molecular perturbations may be linked to antimicrobial peptide pathways and FLT3 signaling, potentially contributing to the favorable outcome in achieving pCR [ 60 , 61 ]. Future work could specifically search for these complex interactions across different molecules to gain more clinically relevant insights into pCR tumors. Supplementary Table S3 available online at http://bib.oxfordjournals.org/ presents the more detailed list (top 30) of the multi-modal and -omics biomarkers identified using the MOMLIN pipeline.

Multimodal network biomarkers explain drug-response classes. The multimodal networks detail the candidate biomarkers and their interactions for each response class, (A) the pCR patients (B) the RCB-I patients (good response), (C) the RCB-II patients (moderate response) and (D) the RCB-III resistance patients. Nodes in the network represent candidate biomarkers derived from clinical features, DNA mutations, gene expression, enriched cell-types and pathways, each indicated in different colors in the figure legend. Negative edges are light green; positive edges are in light magenta. Edge width reflects the strength of the interaction between features. Node size corresponds to the number of connections (degree), and the font size of node labels scales with degree centrality, highlighting the most interconnected biomarkers.

Similarly, RCB-I tumors exhibited co-enriched mutations in MUC16 and TP53, particularly in HER2+ cases [ 14 ]. MUC16 (CA125) is therapeutic molecule associated with immune evasion and tumor growth [ 51 ], while TP53 mutations can lead to loss of cell cycle control and genomic instability [ 62 ]. We also observed elevated expression of TST involved in the detoxification processes and GPX1P1 [long non-coding RNA (lncRNA)] involved in oxidative stress response. The immune landscape of these tumors showed increased infiltration of TEM CD4 cells (adaptive immunity), monocytic lineage cells (phagocytosis and antigen presentation) and NK cells (innate immunity), as well as CAFs. This immune landscape, coupled with potential perturbations in the allograft rejection pathway, suggests an active but potentially incomplete immune response against the tumor, resulting in minimal residual disease.

RCB-II tumors had lower neoantigen loads compared to pCR, both in ER-negative and HER2+ patients. This reduced neoantigen load might contribute to a weaker immune response. Gene expression analysis showed elevated levels of specific lncRNAs, including FTH1P20 (associated with iron metabolism), RNF5P1 (potentially affecting protein degradation) and RPLP0P9 (involved in protein synthesis), along with ERVMER34-1, which can influence gene expression and immune response in BC patients. Numerous studies have underscored the key regulatory roles of lncRNAs in tumors and the immune system. Notably, increased expression of the immune checkpoint protein IDO1 negatively regulates the expression of CTLA-4, both known to modulate antitumor immune responses [ 63 ]. The combined effect of these molecular alterations suggests potential tumor survival mechanisms, including immune evasion and dysregulation of G1/S DNA damage [ 64 ] contributing to moderate residual disease.

In RCB-III tumors, we observed the reduced prevalence of TP53 and MT-ND4 mutations, typically associated with genomic instability and aggressive tumor behavior [ 51 ], coupled with a higher neoantigen load, suggesting an alternative mechanism (pathways) that drives tumor progression. Despite the higher neoantigen loads, increased expression of HLA-E immune checkpoints and T-cell exclusion in the tumor microenvironment hindered effective anti-tumor immune responses. Additionally, the low-expressed genes PON3, ENSG00000261116 (lncRNA) and RNF5P1 are involved in detoxification, gene regulation and protein degradation, respectively, represents an adaptive response to cellular stress in these tumors. Clinical markers indicating lymph node involvement suggest a more advanced disease state [ 9 ]. These findings, along with potential perturbations in the neurotransmitter release cycle pathway, collectively portray RCB-III tumors as genetically unstable, yet effectively evading immune surveillance, contributing to their significant treatment resistance. Overall, further investigation of these interactive molecular networks, comprising both positive and negative interactions offers a more depth understudying of these potential candidate biomarkers for distinguishing treatment-sensitive pCR and resistant RCB tumors.

The advent of multi-omics technologies has revolutionized our understanding of cancer biology, offering unprecedented insights into the complex molecular interactions that shape tumor behavior and treatment response. In this study, we presented MOMLIN (multi-modal and -omics ML integration), a novel method to enhance cancer drug-response prediction by integrating multi-omics data. MOMLIN specifically utilizes class-specific feature learning and sparse correlation algorithms to model multi-omics associations, enables the detection of class-specific multimodal biomarkers from different omics datasets. Applied to a BC multimodal dataset of 147 patients (comprising RNA expression, DNA mutation, tumor microenvironment, clinical features and pathway functional profiles), MOMLIN was highly predictive of responses to anticancer therapies and identified cohesive multi-modal and -omics network biomarkers associated with responder (pCR) and various levels of RCB (RCB-I: good response, RCB-II: moderate response and RCB-III: resistance).

Using MOMLIN, we identified that pCR is determined by an interactive set of multimodal network biomarkers driven by distinct genetic alterations, such as HMCN1 and COL5A1, particularly in ER-negative tumors [ 9 , 65 ]. Gene expression signatures, including FBXO2 and CSF3R were associated with the immune cell infiltration (CD8+ T-cells), which has been previously reported as a key determinant of response [ 57 ]. The association of these biomarkers with antimicrobial peptide and FLT3 signaling pathways suggests a robust immune response [ 61 ] as a critical driver of complete response. Additionally, C2CD4D-AS1, an lncRNA was identified, and its exact role with these complex molecular interactions in BC remains to be elucidated. Future work could specifically search for these complex interactions across different molecules to gain more clinically relevant insights into pCR tumors.

RCB-I tumors, despite responding well to response, were associated with a distinct multimodal molecular signature. These tumors were enriched for mutations in the therapeutic target MUC16 (CA125), known for its role in immune evasion [ 51 ], and the tumor suppressor gene TP53, particularly in HER2+ cases [ 14 ]. Elevated expression of TST and GPX1P1 (lncRNA involved in oxidative stress response) were associated with increased infiltration of diverse immune cells, including Tem CD4+ cells, monocytes and NK cells [ 10 ]. This active immune landscape and the intricate interactions of these signature with the potential perturbations in the allograft rejection pathway, suggests a robust yet potentially incomplete anti-tumor immune response, contributing to the minimal residual disease observed in this subtype.

RCB-II tumors showed lower neoantigen loads compared to pCR, which could contribute to a weaker immune response, particularly in ER-negative and HER2+ subtypes. Increased expression of lncRNAs, such as FTH1P20, RNF5P1, RPLP0P9 and ERVMER34–1, were associated with the immune checkpoint protein IDO1, and negatively regulate the CTLA-4 protein expression, suggests immune evasion and alterations in tumor cell metabolism and proliferation. These molecules altered intricate interactions implicate dysregulation of G1/S DNA damage as a possible mechanism for moderate treatment response [ 64 ].

RCB-III tumors, classified as resistant, were associated with a distinct multimodal molecular landscape driven by reduced TP53 and MT-ND4 mutations [ 52 ], accompanied with higher neoantigen loads compared to other response groups. This suggests an alternative mechanism driving tumor progression and immune evasion. Despite the high neoantigen load which could potentially trigger immune response, these tumors exhibited immune evasion through increased HLA-E immune checkpoints and T-cell exclusion [ 40 , 55 ]. Also, the downregulation of genes like PON3 and the lncRNA ENSG00000261116, along with lymph node involvement, pointed to advanced disease and cellular stress adaptation [ 9 ]. The presence of these complex interactions, including potential perturbations in the neurotransmitter release cycle pathway, could contribute to treatment resistance in RCB-III tumors. Future studies targeting these immunosuppressive mechanisms and exploring novel pathways could offer promising avenues to overcome resistance in this aggressive subtype.

These findings above emphasize the potential of MOMLIN to enable deeper understanding of complex biological mechanism correspondence to each response class, ultimately paving the way for personalized treatment strategies in cancer. MOMLIN also demonstrated the best prediction performance for unseen patients by utilizing these identified sets of network biomarkers. By identifying response-associated biomarkers, researchers can stratify patients based on their likelihood of achieving pCR or experiencing RCB to anticancer treatments, facilitating more informed treatment decisions and potentially improving patient outcomes. Moreover, the identified biomarkers could serve as valuable targets for the development of novel therapeutic interventions and new biological hypothesis generation. However, the clinical translation of multimodal biomarkers necessitates addressing the potential economic burden associated with multi-omics testing. Developing targeted biomarker panels and prioritizing key hub molecules from the large-scale candidate multimodal network biomarkers identified by MOMLIN could be a viable strategy for reducing costs while maintaining predictive accuracy. Furthermore, ongoing advancements in sequencing and diagnostic technologies are expected to make multi-omics testing more accessible and affordable over time.

In conclusion, our study demonstrates MOMLIN’s capacity to uncover nuanced molecular signatures associated with different drug-response classes in BC. By integrating multi-modal and -omics datasets, we have highlighted the complex interplay between genetic alterations, gene expression, immune infiltration and cellular pathways that contribute to treatment response and resistance. Future research in this direction holds promise for refining risk stratification, optimizing treatment selection and ultimately improving patient outcomes.

While MOMLIN demonstrates promising results as shown, a key limitation lies in its reliance on correlation-based algorithms for multi-omics data integration. These algorithms are great at identifying associations, but they can fall short when it comes to inferring causality between different omics layers. This is a challenge faced by most current state-of-the-art methods [ 28 , 30 ]. In the future iterations of MOMLIN, we aim to incorporate causal inference methodologies alongside sparse correlation algorithms to better understand the complex causal relationships within multi-omics datasets.

We proposed MOMLIN, a novel framework designed to integrate multimodal data and identify response-associated network biomarkers, to understand biological mechanisms and regulatory roles.

MOMLIN employed an adaptive weighting for different data modalities and employs innovative regularization constraint to ensure robust feature selection to analyze high-dimensional omics data.

MOMLIN demonstrates significantly improved performance compared to current state-of-the-art methods.

MOMLIN identifies interpretable and phenotype-specific components, providing insights into the molecular mechanisms driving treatment response and resistance.

We thank Dr Yoshihiro Yamnishi and Mr Chen Yuzhou for their technical help.

This work was supported by the core research budget of Bioinformatics Institute, ASTAR.

Supplemental information and software are available at the Bib website. Our algorithm’s software is available for free download at https://github.com/mamun41/MOMLIN_softwar/tree/main

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The construction and application of a model for evaluating tourism climate suitability in terraced agricultural cultural heritage sites: a case study of longji terraced fields in china.

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Hu, L.; Guo, X.; Yan, P.; Li, X. The Construction and Application of a Model for Evaluating Tourism Climate Suitability in Terraced Agricultural Cultural Heritage Sites: A Case Study of Longji Terraced Fields in China. Atmosphere 2024 , 15 , 756. https://doi.org/10.3390/atmos15070756

Hu L, Guo X, Yan P, Li X. The Construction and Application of a Model for Evaluating Tourism Climate Suitability in Terraced Agricultural Cultural Heritage Sites: A Case Study of Longji Terraced Fields in China. Atmosphere . 2024; 15(7):756. https://doi.org/10.3390/atmos15070756

Hu, Luyao, Xiaoyu Guo, Pengbo Yan, and Xinkai Li. 2024. "The Construction and Application of a Model for Evaluating Tourism Climate Suitability in Terraced Agricultural Cultural Heritage Sites: A Case Study of Longji Terraced Fields in China" Atmosphere 15, no. 7: 756. https://doi.org/10.3390/atmos15070756

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Published on 24.6.2024 in Vol 26 (2024)

Multicentric Assessment of a Multimorbidity-Adjusted Disability Score to Stratify Depression-Related Risks Using Temporal Disease Maps: Instrument Validation Study

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