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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 and Reimand, Jüri (2020) In Nature Communications 11.
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... (More)

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.

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publication status
published
subject
keywords
Adenocarcinoma/genetics, Apoptosis/genetics, Breast Neoplasms/genetics, Chromatin Immunoprecipitation, Computational Biology/methods, Databases, Factual, Female, Gene Dosage, Gene Expression Profiling, Gene Regulatory Networks, Genomics/methods, Hippo Signaling Pathway, Humans, Metabolic Networks and Pathways/genetics, Mutation, Neoplasms/genetics, Prognosis, Protein Serine-Threonine Kinases/genetics, RNA, Messenger/genetics, Sequence Analysis, RNA, Signal Transduction
in
Nature Communications
volume
11
article number
735
pages
16 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85079073313
  • pmid:32024846
ISSN
2041-1723
DOI
10.1038/s41467-019-13983-9
language
English
LU publication?
yes
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b486ce00-a859-4987-a982-7e1d4081e7a8
date added to LUP
2023-01-05 14:36:53
date last changed
2024-04-18 18:30:55
@article{b486ce00-a859-4987-a982-7e1d4081e7a8,
  abstract     = {{<p>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.</p>}},
  author       = {{Paczkowska, Marta and Barenboim, Jonathan and Sintupisut, Nardnisa and Fox, Natalie S and Zhu, Helen and Abd-Rabbo, Diala and Mee, Miles W and Boutros, Paul C and Reimand, Jüri}},
  issn         = {{2041-1723}},
  keywords     = {{Adenocarcinoma/genetics; Apoptosis/genetics; Breast Neoplasms/genetics; Chromatin Immunoprecipitation; Computational Biology/methods; Databases, Factual; Female; Gene Dosage; Gene Expression Profiling; Gene Regulatory Networks; Genomics/methods; Hippo Signaling Pathway; Humans; Metabolic Networks and Pathways/genetics; Mutation; Neoplasms/genetics; Prognosis; Protein Serine-Threonine Kinases/genetics; RNA, Messenger/genetics; Sequence Analysis, RNA; Signal Transduction}},
  language     = {{eng}},
  month        = {{02}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Integrative pathway enrichment analysis of multivariate omics data}},
  url          = {{http://dx.doi.org/10.1038/s41467-019-13983-9}},
  doi          = {{10.1038/s41467-019-13983-9}},
  volume       = {{11}},
  year         = {{2020}},
}