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Integrative pathway enrichment analysis of multivariate omics data

By Marta Paczkowska, Jonathan Barenboim, Nardnisa Sintupisut, Natalie C Fox, Helen Zhu, Diala Abd-Rabbo, PCAWG Network and Pathway Analysis Group, Paul C. Boutros, Jüri Reimand

Posted 23 Aug 2018
bioRxiv DOI: 10.1101/399113 (published DOI: 10.1038/s41467-019-13983-9)

Multi-omics datasets quantify complementary aspects of molecular biology and thus pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple omics datasets using a statistical data fusion approach, rationalizes contributing evidence and highlights associated genes. We demonstrate its utility by analyzing coding and non-coding mutations from 2,583 whole cancer genomes, revealing frequently mutated hallmark pathways and a long tail of known and putative cancer driver genes. We also studied prognostic molecular pathways in breast cancer subtypes by integrating genomic and transcriptomic features of tumors and tumor-adjacent cells and found significant associations with immune response processes and anti-apoptotic signaling pathways. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.

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