Analysis of time-resolved gene expression measurements across individuals.

Abstract

Genetic and environmental determinants of altered cellular function, disease state, and drug response are increasingly studied using time-resolved transcriptomic profiles. While it is widely acknowledged that the rate of biological processes may vary between individuals, data analysis approaches that go beyond evaluating differential expression of single genes have so far not taken this variability into account. To this end, we introduce here a robust multi-gene data analysis approach and evaluate it in a biomarker discovery scenario across four publicly available datasets. In our evaluation, existing methods perform surprisingly poorly on time-resolved data; only the approach taking the variability into account yields reproducible and biologically plausible results. Our results indicate the need to capture gene expression between potentially heterogeneous individuals at multiple time points, and highlight the importance of robust data analysis in the presence of heterogeneous gene expression responses.