Integrative pathway enrichment analysis of multivariate omics data

Paczkowska, Marta; Barenboim, Jonathan; Sintupisut, Nardnisa; Fox, Natalie S.; Zhu, Helen; Abd-Rabbo, Diala; Mee, Miles W.; Boutros, Paul C.; PCAWG Drivers and Functional Interpretation Working Group; Reimand, Jüri; PCAWG Consortium; Deu-Pons, Jordi; Gonzalez-Perez, Abel; Gut, Ivo Glynne; Muiños, Ferran; Mularoni, Loris; Pich, Oriol; Rubio Pérez, Carlota; Sabarinathan, Radhakrishnan; Tamborero Noguera, David

Integrative pathway enrichment analysis of multivariate omics data

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dc.contributor.author Paczkowska, Marta
dc.contributor.author Barenboim, Jonathan
dc.contributor.author Sintupisut, Nardnisa
dc.contributor.author Fox, Natalie S.
dc.contributor.author Zhu, Helen
dc.contributor.author Abd-Rabbo, Diala
dc.contributor.author Mee, Miles W.
dc.contributor.author Boutros, Paul C.
dc.contributor.author PCAWG Drivers and Functional Interpretation Working Group
dc.contributor.author Reimand, Jüri
dc.contributor.author PCAWG Consortium
dc.contributor.author Deu-Pons, Jordi
dc.contributor.author Gonzalez-Perez, Abel
dc.contributor.author Gut, Ivo Glynne
dc.contributor.author Muiños, Ferran
dc.contributor.author Mularoni, Loris
dc.contributor.author Pich, Oriol
dc.contributor.author Rubio Pérez, Carlota
dc.contributor.author Sabarinathan, Radhakrishnan
dc.contributor.author Tamborero Noguera, David
dc.date.accessioned 2020-04-24T07:19:07Z
dc.date.available 2020-04-24T07:19:07Z
dc.date.issued 2020
dc.description.abstract 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 genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. 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.
dc.description.sponsorship This work was funded by a 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
dc.format.mimetype application/pdf
dc.identifier.citation Paczkowska M, Barenboim J, Sintupisut N, Fox NS, Zhu H, Abd-Rabbo D et al. Integrative pathway enrichment analysis of multivariate omics data. Nat Commun. 2020 Feb 5; 11(1): 735. DOI: 10.1038/s41467-019-13983-9
dc.identifier.doi http://dx.doi.org/10.1038/s41467-019-13983-9
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/44322
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nature Communications. 2020 Feb 5;11(1):735
dc.rights © 2020 Marta Paczkowska et al. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Càncer
dc.subject.other Genètica
dc.subject.other Genòmica
dc.subject.other Biologia molecular
dc.title Integrative pathway enrichment analysis of multivariate omics data
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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