MR4Cancer: A web server prioritizing master regulators for cancer

Abstract

During cancer stage transition, a master regulator (MR) refers to the key gene controlling cancer initiation and progression by orchestrating the associated target genes (termed as its regulon). Due to their inherent importance, MRs can serve as critical biomarkers for cancer diagnosis and prognosis, and therapeutic targets. However, it is challenging to infer key MRs that might explain gene expression profile changes between two groups due to lack of context-specific regulons, whose expression level can collectively reflect the activity of likely MRs. There is also a need to design an easy-to-use tool of MR identification for research community. Results: First, we generated cancer-specific regulons for 26 cancer types by analyzing highthroughput omics data from TCGA, and extracted noncancer-specific regulons from public databases. We subsequently developed a web server MR4Cancer, integrating the regulons with statistical inference to identify and prioritize MRs driving a phenotypic divergence of interest. Based on the input gene list (e.g. differentially expressed genes) or expression profile with two groups, MR4Cancer outputs rankedMRs by enrichment testing against the predefined regulons. Gene Ontology and canonical pathway analyses are also conducted to elucidate the function of likely MRs. Moreover, MR4Cancer provides dynamic network visualization for MR-target relations, and users can interactively interrogate the network to produce new hypotheses and high-quality figures for publication. Finally, the presented case studies highlighted the performance of MR4Cancer. We expect this user-friendly and powerful web tool will provide researchers novel insights into tumorigenesis and therapeutic intervention.