CNApp, a tool for the quantification of copy number alterations and integrative analysis revealing clinical implications

  1. Sebastià Franch-Expósito
  2. Laia Bassaganyas
  3. Maria Vila-Casadesús
  4. Eva Hernández-Illán
  5. Roger Esteban-Fabró
  6. Marcos Díaz-Gay
  7. Juan José Lozano
  8. Antoni Castells
  9. Josep Maria Llovet
  10. Sergi Castellvi-Bel  Is a corresponding author
  11. Jordi Camps  Is a corresponding author
  1. 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
  2. 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).

The following previously published data sets were used

Article and author information

Author details

  1. Sebastià Franch-Expósito

    Gastrointestinal and Pancreatic Oncology Team, 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, Barcelona, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4542-1701
  2. Laia Bassaganyas

    Liver Cancer Translational Research Group, Liver Unit, 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, Barcelona, Spain
    Competing interests
    No competing interests declared.
  3. Maria Vila-Casadesús

    Bioinformatics Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
    Competing interests
    No competing interests declared.
  4. Eva Hernández-Illán

    Gastrointestinal and Pancreatic Oncology Team, 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, Barcelona, Spain
    Competing interests
    No competing interests declared.
  5. Roger Esteban-Fabró

    Liver Cancer Translational Research Group, Liver Unit, 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, Barcelona, Spain
    Competing interests
    No competing interests declared.
  6. Marcos Díaz-Gay

    Gastrointestinal and Pancreatic Oncology Team, 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, Barcelona, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0658-0467
  7. Juan José Lozano

    Bioinformatics Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
    Competing interests
    No competing interests declared.
  8. Antoni Castells

    Gastrointestinal and Pancreatic Oncology Team, 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, Barcelona, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8431-2033
  9. Josep Maria Llovet

    Liver Cancer Translational Research Group, Liver Unit, 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, Barcelona, Spain
    Competing interests
    Josep Maria Llovet, is receiving research support from Bayer HealthCare Pharmaceuticals, Eisai Inc, Bristol-Myers Squibb and Ipsen, and consulting fees from Eli Lilly, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, EISAI Inc, Celsion Corporation, Exelixis, Merck, Ipsen, Glycotest, Navigant, Leerink Swann LLC, Midatech Ltd, and Nucleix.
  10. Sergi Castellvi-Bel

    Gastrointestinal and Pancreatic Oncology Team, 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, Barcelona, Spain
    For correspondence
    SBEL@clinic.cat
    Competing interests
    No competing interests declared.
  11. Jordi Camps

    Gastrointestinal and Pancreatic Oncology Team, 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, Barcelona, Spain
    For correspondence
    JCAMPS@clinic.cat
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2929-4228

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

  1. C Daniela Robles-Espinoza, International Laboratory for Human Genome Research, Mexico

Publication history

  1. Received: July 17, 2019
  2. Accepted: January 14, 2020
  3. Accepted Manuscript published: January 15, 2020 (version 1)
  4. 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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  1. Sebastià Franch-Expósito
  2. Laia Bassaganyas
  3. Maria Vila-Casadesús
  4. Eva Hernández-Illán
  5. Roger Esteban-Fabró
  6. Marcos Díaz-Gay
  7. Juan José Lozano
  8. Antoni Castells
  9. Josep Maria Llovet
  10. Sergi Castellvi-Bel
  11. Jordi Camps
(2020)
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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