CNApp, a tool for the quantification of copy number alterations and integrative analysis revealing clinical implications
- Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universitat de Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
Abstract
Somatic copy number alterations (CNAs) are a hallmark of cancer, but their role in tumorigenesis and clinical relevance remain largely unclear. Here we developed CNApp, a web-based tool that allows a comprehensive exploration of CNAs by using purity-corrected segmented data from multiple genomic platforms. CNApp generates genome-wide profiles, computes CNA scores for broad, focal and global CNA burdens, and uses machine learning-based predictions to classify samples. We applied CNApp to the TCGA pan-cancer dataset of 10,635 genomes showing that CNAs classify cancer types according to their tissue-of-origin, and that each cancer type shows specific ranges of broad and focal CNA scores. Moreover, CNApp reproduces recurrent CNAs in hepatocellular carcinoma, and predicts colon cancer molecular subtypes and microsatellite instability based on broad CNA scores and discrete genomic imbalances. In summary, CNApp facilitates CNA-driven research by providing a unique framework to identify relevant clinical implications. CNApp is hosted at https://tools.idibaps.org/CNApp/.
Data availability
Data and plots presented in the submission were generated by using our CNApp tool. Source code and additional files can be found at GitHub (https://github.com/ait5/CNApp).
Article and author information
Author details
Sebastià Franch-Expósito
Funding
CIBEREHD
- Sebastià Franch-Expósito
Fundacion Cientifica de la Asociacion Espanola Contra el Cancer (GCB13131592CAST)
- Juan José Lozano
- Antoni Castells
- Sergi Castellvi-Bel
- Jordi Camps
European Commission /Horizon 2020 Program (HEPCAR Ref. 667273-2)
- Josep Maria Llovet
U.S. Department of Defense (CA150272P3)
- Josep Maria Llovet
National Cancer Institute (P30-CA196521)
- Josep Maria Llovet
Samuel Waxman Cancer Research Foundation
- Josep Maria Llovet
Spanish National Health Institute (SAF2016-76390)
- Josep Maria Llovet
Generalitat de Catalunya/AGAUR (SGR-1162)
- Josep Maria Llovet
Generalitat de Catalunya/AGAUR (SGR-1358)
- Josep Maria Llovet
European Regional Development Fund (PI14/00783)
- Marcos Díaz-Gay
- Juan José Lozano
- Antoni Castells
- Sergi Castellvi-Bel
- Jordi Camps
European Regional Development Fund (PI17/01304)
- Marcos Díaz-Gay
- Juan José Lozano
- Antoni Castells
- Sergi Castellvi-Bel
- Jordi Camps
Generalitat de Catalunya (AGAUR 2016BP00161)
- Laia Bassaganyas
European Regional Development Fund (PI17/00878)
- Marcos Díaz-Gay
- Juan José Lozano
- Antoni Castells
- Sergi Castellvi-Bel
- Jordi Camps
Generalitat de Catalunya (2017 SGR 21)
- Juan José Lozano
- Antoni Castells
- Sergi Castellvi-Bel
- Jordi Camps
Generalitat de Catalunya (2017 SGR 653)
- Juan José Lozano
- Antoni Castells
- Sergi Castellvi-Bel
- Jordi Camps
Generalitat de Catalunya (AGAUR 2018FI B1_00213)
- Marcos Díaz-Gay
Spanish National Health Institute (FPI BES-2017-081286)
- Roger Esteban-Fabró
European Comission (PCIG11-GA-2012-321937)
- Juan José Lozano
- Antoni Castells
- Sergi Castellvi-Bel
- Jordi Camps
European Regional Development Fund (CP13/00160)
- Marcos Díaz-Gay
- Juan José Lozano
- Antoni Castells
- Sergi Castellvi-Bel
- Jordi Camps
CERCA Program
- Juan José Lozano
- Antoni Castells
- Josep Maria Llovet
- Sergi Castellvi-Bel
- Jordi Camps
Generalitat de Catalunya (2017 SGR 1035)
- Juan José Lozano
- Antoni Castells
- Sergi Castellvi-Bel
- Jordi Camps
PERIS Generalitat de Catalunya (SLT002/16/00398)
- Juan José Lozano
- Antoni Castells
- Sergi Castellvi-Bel
- Jordi Camps
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- C Daniela Robles-Espinoza, International Laboratory for Human Genome Research, Mexico
Publication history
- Received: July 17, 2019
- Accepted: January 14, 2020
- Accepted Manuscript published: January 15, 2020 (version 1)
- Version of Record published: February 10, 2020 (version 2)
Copyright
© 2020, Franch-Expósito et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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CNApp, a tool for the quantification of copy number alterations and integrative analysis revealing clinical implications
eLife 9:e50267.
https://doi.org/10.7554/eLife.50267
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