Discerning mechanistically rewired biological pathways by cumulative interaction heterogeneity statistics.

ABSTRACT: Changes in response of a biological pathway could be a consequence of either pathway rewiring, changed input, or a combination of both. Most pathway analysis methods are not designed for mechanistic rewiring such as regulatory element variations. This limits our understanding of biological pathway evolution. Here we present a Q-method to discern whether changed pathway response is caused by mechanistic rewiring of pathways due to evolution. The main innovation is a cumulative pathway interaction heterogeneity statistic accounting for rewiring-specific effects on the rate of change of each molecular variable across conditions. The Q-method remarkably outperformed differential-correlation based approaches on data from diverse biological processes. Strikingly, it also worked well in different

SUBMITTER: Cotton TB 

PROVIDER: S-EPMC4894439 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature