A novel significance score for gene selection and ranking

Y Xiao, TH Hsiao, U Suresh, HIH Chen, X Wu… - …, 2014 - academic.oup.com
Y Xiao, TH Hsiao, U Suresh, HIH Chen, X Wu, SE Wolf, Y Chen
Bioinformatics, 2014academic.oup.com
Motivation: When identifying differentially expressed (DE) genes from high-throughput gene
expression measurements, we would like to take both statistical significance (such as P-
value) and biological relevance (such as fold change) into consideration. In gene set
enrichment analysis (GSEA), a score that can combine fold change and P-value together is
needed for better gene ranking. Results: We defined a gene significance score π-value by
combining expression fold change and statistical significance (P-value), and explored its …
Abstract
Motivation: When identifying differentially expressed (DE) genes from high-throughput gene expression measurements, we would like to take both statistical significance (such as P-value) and biological relevance (such as fold change) into consideration. In gene set enrichment analysis (GSEA), a score that can combine fold change and P-value together is needed for better gene ranking.
Results: We defined a gene significance score π-value by combining expression fold change and statistical significance (P-value), and explored its statistical properties. When compared to various existing methods, π-value based approach is more robust in selecting DE genes, with the largest area under curve in its receiver operating characteristic curve. We applied π-value to GSEA and found it comparable to P-value and t-statistic based methods, with added protection against false discovery in certain situations. Finally, in a gene functional study of breast cancer profiles, we showed that using π-value helps elucidating otherwise overlooked important biological functions.
Availability:  http://gccri.uthscsa.edu/Pi_Value_Supplementary.asp
Contact:  xy@ieee.org, cheny8@uthscsa.edu
Supplementary information:  Supplementary data are available at Bioinformatics online.
Oxford University Press