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Elife. 2020 Jan 15;9. pii: e50267. doi: 10.7554/eLife.50267.

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

Author information

1
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.
2
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.
3
Bioinformatics Unit, CIBEREHD, Barcelona, Spain.
4
Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, United States.
5
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
6
Unitat de Biologia Cel·lular i Genètica Mèdica, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
#
Contributed equally

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/.

plain-language-summary:

In most cases, human cells contain two copies of each of their genes, yet sometimes this can change, an effect called copy number alteration (CNA). Cancer is a genetic disease and thus, studying the DNA from tumor samples is crucial to improving diagnosis and choosing the right treatment. Most tumors contain cells with CNAs; however, the impact of CNAs in cancer progression is poorly understood. CNAs can be studied by examining the genome of tumor cells and finding which regions display an unusual number of copies. It may also be possible to gather information about different cancer types by analyzing the CNAs in a tumor, but this approach requires the analysis of large amounts of data. To aid the analysis of CNAs in cancer cells, Franch-Expósito, Bassaganyas et al. have created an online tool called CNApp, which is able to identify and count CNAs in genomic data and link them to features associated with different cancers. The hope is that a better understanding of the effect of CNAs in cancer could help better diagnose cancers, and improve outcomes for patients. Potentially, this could also predict what type of treatment would work better for a specific tumor. Besides, by using a machine-learning approach, the tool can also make predictions about specific cancer subtypes in order to facilitate clinical decisions. Franch-Expósito, Bassaganyas et al. tested CNApp using previously existing cancer data from 33 different cancer types to show how CNApp can help the interpretation of CNAs in cancer. Moreover, CNApp can also use CNAs to identify different types of bowel (colorectal) cancer in a way that could help doctors to make decisions about treatment. Together these findings show that CNApp provides an adaptable and accessible research tool for the study of cancer genomics, which could provide opportunities to inform medical procedures.

KEYWORDS:

CNA scores; cancer genomics; colorectal cancer; computational biology; copy number alterations; genetics; genomics; hepatocellular carcinoma; human; pan-cancer; systems biology

Conflict of interest statement

SF, LB, MV, EH, RE, MD, JL, AC, SC, JC No competing interests declared, JL 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

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