ORCID Profile
0000-0002-5713-1058
Current Organisations
Norwegian University of Science and Technology
,
Centro Nacional de Supercomputación
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Publisher: Cold Spring Harbor Laboratory
Date: 17-01-0301
DOI: 10.1101/2020.10.26.356014
Abstract: We describe a large-scale community effort to build an open-access, interoperable, and computable repository of COVID-19 molecular mechanisms - the COVID-19 Disease Map. We discuss the tools, platforms, and guidelines necessary for the distributed development of its contents by a multi-faceted community of biocurators, domain experts, bioinformaticians, and computational biologists. We highlight the role of relevant databases and text mining approaches in enrichment and validation of the curated mechanisms. We describe the contents of the Map and their relevance to the molecular pathophysiology of COVID-19 and the analytical and computational modelling approaches that can be applied for mechanistic data interpretation and predictions. We conclude by demonstrating concrete applications of our work through several use cases and highlight new testable hypotheses.
Publisher: Springer Science and Business Media LLC
Date: 08-12-2022
Publisher: Elsevier BV
Date: 05-2021
Publisher: EMBO
Date: 10-2021
Publisher: Springer Science and Business Media LLC
Date: 30-07-2013
DOI: 10.1038/NMETH.2562
Publisher: Springer Science and Business Media LLC
Date: 05-02-2020
DOI: 10.1038/S41467-020-14367-0
Abstract: The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53 , TLE4 , and TCF4 . We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and s les containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as s les with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
No related grants have been discovered for Miguel Vazquez.