Comparative Pathway Integrator: A Framework of Meta-Analytic Integration of Multiple Transcriptomic Studies for...

Pathway enrichment analysis provides a knowledge-driven approach to interpret differentially expressed genes associated with disease status. Many tools have been developed to analyze a single study. However, when multiple studies of different conditions are jointly analyzed, novel integrative tools are needed. In addition, pathway redundancy introduced by combining multiple public pathway databases hinders interpretation and knowledge discovery. We present a meta-analytic integration tool, Comparative Pathway Integrator (CPI), to address these issues using adaptively weighted Fisher's method to discover consensual and differential enrichment patterns, a tight clustering algorithm to reduce pathway redundancy, and a text mining algorithm to assist interpretation of the pathway clusters. We applied CPI to jointly analyze six psychiatric disorder transcriptomic studies to demonstrate its effectiveness, and found functions confirmed by previous biological studies as well as novel enrichment patterns. CPI's R package is accessible online on Github metaOmics/MetaPath.