Pathway-Informed Classification System (PICS) for Cancer Analysis Using Gene Expression Data

Abstract

We introduce Pathway-Informed Classification System (PICS) for classifying cancers based on tumor sample gene expression levels. PICS is a computational method capable of expeditiously elucidating both known and novel biological pathway involvement specific to various cancers and uses that learned pathway information to separate patients into distinct classes. The method clearly separates a pan-cancer dataset by tissue of origin and also sub-classifies individual cancer datasets into distinct survival classes. Gene expression values are collapsed into pathway scores that reveal which biological activities are most useful for clustering cancer cohorts into subtypes. Variants of the method allow it to be used on datasets that do and do not contain noncancerous samples. Activity levels of all types of pathways, broadly grouped into metabolic, cellular processes and signaling, and immune system, are useful for separating the pan-cancer cohort. In the clustering of specific cancer types, certain pathway types become more valuable depending on the site being studied. For lung cancer, signaling pathways dominate; for pancreatic cancer, signaling and metabolic pathways dominate; and for melanoma, immune system pathways are the most useful. This work suggests the utility of pathway-level genomic analysis and points in the direction of using pathway classification for predicting the efficacy and side effects of drugs and radiation.