Document information

5 votes

The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies

Leming D. Shi¹, Wendell D. Jones², Roderick V. Jensen³, Stephen C. Harris¹, Roger G. Perkins⁴, Federico M. Goodsaid⁵, Lei Guo¹, Lisa J. Croner⁶, Cecilie Boysen⁷, Hong Fang⁴, Shashi Amur⁵, Wenjun Bao⁸, Catalin C. Barbacioru⁹, Vincent Bertholet¹⁰, Xiaoxi Megan Cao⁴, Tzu-Ming Chu⁸, Patrick J. Collins¹¹, Xiao-hui Fan¹, Felix W. Frueh⁵, James C. Fuscoe¹, Xu Guo¹², Jing Han¹³, Damir Herman¹⁴, Huixiao Hong⁴, Ernest S. Kawasaki¹⁵, Quan-Zhen Li¹⁶, Yuling Luo¹⁷, Yunqing Ma¹⁷, Nan Mei¹, Ron L. Peterson¹⁸, Raj K. Puri¹³, Feng Qian⁴, Richard Shippy¹², Zhenqiang Su¹, Yongming Andrew Sun⁹, Hongmei Sun⁴, Brett Thorn¹, Yaron Turpaz¹², Charles Wang¹⁹, Sue-Jane Wang⁵, Janet A. Warrington¹², James C. Willey²⁰, Jie Wu⁴, Qian Xie⁴, Liang Zhang²¹, Lu Zhang²², Sheng Zhong²³, Russell D. Wolfinger⁸, & Weida Tong¹

Correspondence: (Login to view email address)

1. US FDA, National Center for Toxicological Research
2. Expression Analysis Inc.
3. Virginia Bioinformatics Institute
4. Z-Tech at FDA/NCTR
5. US FDA, Center for Drug Evaluation and Research
6. Biogen Idec
7. ViaLogy Inc.
8. SAS Institute Inc.
9. Applied Biosystems
10. Eppendorf Array Technologies
11. Agilent Technologies Inc.
12. Affymetrix Inc.
13. US FDA, Center for Biologics Evaluation and Research
14. University of Arkansas for Medical Sciences
15. US NIH, National Cancer Institute
16. University Texas Southwestern Medical Center
17. Panomics Inc.
18. Novartis
19. UCLA Cedars-Sinai Medical Center
20. University of Toledo
21. CapitalBio Corporation
22. Solexa Inc.
23. University of Illinois at Urbana-Champaign

PDF (2.1 MB)

Document Type:

Manuscript

Date:

Received 02 July 2007 15:49 UTC; Posted 03 July 2007

Subjects:

Biotechnology, Bioinformatics

Tags:

• gene selection
• fold change
• microarrays
• reproducibility
• MAQC
• statistics
• P-value

Abstract:

Reproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity.

Discussion

Votes:

5 votes

(Login to vote)

Comments:

0 comments

(Login to post a comment)

Share:

(Login to share with a colleague)

Additional information

License:

This document is licensed to the public under the Creative Commons Attribution 2.5 License

How to cite this document:

Shi, Leming, Jones, Wendell, Jensen, Roderick, Harris, Stephen, Perkins, Roger, Goodsaid, Federico, Guo, Lei, Croner, Lisa, Boysen, Cecilie, Fang, Hong, Amur, Shashi, Bao, Wenjun, Barbacioru, Catalin, Bertholet, Vincent, Cao, Xiaoxi Megan, Chu, Tzu-Ming, Collins, Patrick, Fan, Xiao-hui, Frueh, Felix, Fuscoe, James, Guo, Xu, Han, Jing, Herman, Damir, Hong, Huixiao, Kawasaki, Ernest, Li, Quan-Zhen, Luo, Yuling, Ma, Yunqing, Mei, Nan, Peterson, Ron, Puri, Raj, Qian, Feng, Shippy, Richard, Su, Zhenqiang, Sun, Yongming Andrew, Sun, Hongmei, Thorn, Brett, Turpaz, Yaron, Wang, Charles, Wang, Sue-Jane, Warrington, Janet, Willey, James, Wu, Jie, Xie, Qian, Zhang, Liang, Zhang, Lu, Zhong, Sheng, Wolfinger, Russell, and Tong, Weida. The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2007.306.2> (2007)

Version info:

Other versions of this document in Nature Precedings

Version number	Document title	Date
v1	Posted 02 July 2007

Other versions of this document elsewhere on the web

None known.

Submit a new version link