Integrative pathway enrichment analysis of multivariate omics data
Marta Paczkowska, Jonathan Barenboim, Nardnisa Sintupisut, Natalie S Fox, Helen Zhu, Diala Abd-Rabbo, Miles W Mee, Paul C Boutros, Juri Reimand
NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2020
Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer ge..View full abstract
Awarded by Cancer Research Society (CRS)
Awarded by Natural Sciences and Engineering Research Council of Canada (NSERC)
We would like to thank Drs. Benjamin Raphael, Matthew Reyna, Lincoln Stein and Josh Stuart for valuable discussions on the manuscript. This work was funded by Ontario Institute for Cancer Research (OICR) Investigator Awards to J.R. and P.C.B. provided by the Government of Ontario; Operating Grant to J.R. from Cancer Research Society (CRS) (#21089); Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant to J.R. (#RGPIN-2016-06485), and the Canada First Research Excellence Fund, University of Toronto Medicine by Design to J.R. H.Z. was supported by a CIHR Canadian Graduate Scholarship. J.B. was supported by a BioTalent Canada Student Internship. P.C.B. was supported by TFRI and CIHR New Investigator Awards. We acknowledge the contributions of the many clinical networks across ICGC and TCGA who provided samples and data to the PCAWG Consortium, and the contributions of the Technical Working Group and the Germline Working Group of the PCAWG Consortium for collation, realignment and harmonized variant calling of the cancer genomes used in this study. We thank the patients and their families for their participation in the individual ICGC and TCGA projects.