Interpreting pathways to discover cancer driver genes with Moonlight

Antonio Colaprico; Catharina Olsen; Matthew H. Bailey; Gabriel J. Odom; Thilde Terkelsen; Tiago C. Silva; André V. Olsen; Laura Cantini; Andrei Zinovyev; Emmanuel Barillot; Houtan Noushmehr; Gloria Bertoli; Isabella Castiglioni; Claudia Cava; Gianluca Bontempi; Xi Steven Chen; Elena Papaleo

doi:10.1038/s41467-019-13803-0

Interpreting pathways to discover cancer driver genes with Moonlight

Antonio Colaprico, Catharina Olsen, Matthew H. Bailey, Gabriel J. Odom, Thilde Terkelsen, Tiago C. Silva, André V. Olsen, Laura Cantini, Andrei Zinovyev, Emmanuel Barillot, Houtan Noushmehr, Gloria Bertoli, Isabella Castiglioni, Claudia Cava, Gianluca Bontempi, Xi Steven Chen, Elena Papaleo

Public Health Sciences

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Abstract

Cancer driver gene alterations influence cancer development, occurring in oncogenes, tumor suppressors, and dual role genes. Discovering dual role cancer genes is difficult because of their elusive context-dependent behavior. We define oncogenic mediators as genes controlling biological processes. With them, we classify cancer driver genes, unveiling their roles in cancer mechanisms. To this end, we present Moonlight, a tool that incorporates multiple -omics data to identify critical cancer driver genes. With Moonlight, we analyze 8000+ tumor samples from 18 cancer types, discovering 3310 oncogenic mediators, 151 having dual roles. By incorporating additional data (amplification, mutation, DNA methylation, chromatin accessibility), we reveal 1000+ cancer driver genes, corroborating known molecular mechanisms. Additionally, we confirm critical cancer driver genes by analysing cell-line datasets. We discover inactivation of tumor suppressors in intron regions and that tissue type and subtype indicate dual role status. These findings help explain tumor heterogeneity and could guide therapeutic decisions.

Original language	English (US)
Article number	69
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13803-0
State	Published - Dec 1 2020

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/s41467-019-13803-0

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Colaprico, A., Olsen, C., Bailey, M. H., Odom, G. J., Terkelsen, T., Silva, T. C., Olsen, A. V., Cantini, L., Zinovyev, A., Barillot, E., Noushmehr, H., Bertoli, G., Castiglioni, I., Cava, C., Bontempi, G., Chen, X. S., & Papaleo, E. (2020). Interpreting pathways to discover cancer driver genes with Moonlight. Nature communications, 11(1), [69]. https://doi.org/10.1038/s41467-019-13803-0

Interpreting pathways to discover cancer driver genes with Moonlight. / Colaprico, Antonio; Olsen, Catharina; Bailey, Matthew H.; Odom, Gabriel J.; Terkelsen, Thilde; Silva, Tiago C.; Olsen, André V.; Cantini, Laura; Zinovyev, Andrei; Barillot, Emmanuel; Noushmehr, Houtan; Bertoli, Gloria; Castiglioni, Isabella; Cava, Claudia; Bontempi, Gianluca; Chen, Xi Steven; Papaleo, Elena.

In: Nature communications, Vol. 11, No. 1, 69, 01.12.2020.

Research output: Contribution to journal › Article › peer-review

Colaprico, Antonio ; Olsen, Catharina ; Bailey, Matthew H. ; Odom, Gabriel J. ; Terkelsen, Thilde ; Silva, Tiago C. ; Olsen, André V. ; Cantini, Laura ; Zinovyev, Andrei ; Barillot, Emmanuel ; Noushmehr, Houtan ; Bertoli, Gloria ; Castiglioni, Isabella ; Cava, Claudia ; Bontempi, Gianluca ; Chen, Xi Steven ; Papaleo, Elena. / Interpreting pathways to discover cancer driver genes with Moonlight. In: Nature communications. 2020 ; Vol. 11, No. 1.

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title = "Interpreting pathways to discover cancer driver genes with Moonlight",

abstract = "Cancer driver gene alterations influence cancer development, occurring in oncogenes, tumor suppressors, and dual role genes. Discovering dual role cancer genes is difficult because of their elusive context-dependent behavior. We define oncogenic mediators as genes controlling biological processes. With them, we classify cancer driver genes, unveiling their roles in cancer mechanisms. To this end, we present Moonlight, a tool that incorporates multiple -omics data to identify critical cancer driver genes. With Moonlight, we analyze 8000+ tumor samples from 18 cancer types, discovering 3310 oncogenic mediators, 151 having dual roles. By incorporating additional data (amplification, mutation, DNA methylation, chromatin accessibility), we reveal 1000+ cancer driver genes, corroborating known molecular mechanisms. Additionally, we confirm critical cancer driver genes by analysing cell-line datasets. We discover inactivation of tumor suppressors in intron regions and that tissue type and subtype indicate dual role status. These findings help explain tumor heterogeneity and could guide therapeutic decisions.",

author = "Antonio Colaprico and Catharina Olsen and Bailey, {Matthew H.} and Odom, {Gabriel J.} and Thilde Terkelsen and Silva, {Tiago C.} and Olsen, {Andr{\'e} V.} and Laura Cantini and Andrei Zinovyev and Emmanuel Barillot and Houtan Noushmehr and Gloria Bertoli and Isabella Castiglioni and Claudia Cava and Gianluca Bontempi and Chen, {Xi Steven} and Elena Papaleo",

note = "Funding Information: We are grateful to Matthieu Defrance, Kridsadakorn Chaichoompu, Kristel Van Steen, Benjamin Haibe-Kains ans Thuc Duy Le for suggestions and scientific advice in the Moonlight project. We would also like to thank Lisa Cantwell for her scientific proofreading of the paper. The project was supported by the BridgeIRIS project [http://mlg. ulb.ac.be/BridgeIRIS], funded by INNOVIRIS, Region de Bruxelles Capitale, Brussels, Belgium, and by GENGISCAN: GENomic profiling of Gastrointestinal Inflammatory-Sensitive CANcers, [http://mlg.ulb.ac.be/GENGISCAN] Belgian FNRS PDR (T100914F to A.C., C.O., and Gi.B.). Gi.B. was also supported by the project WALINNOV 2017 – N° 1710030 - CAUSEL I.C, C.C. and Gl.B. were supported by INTEROMICS flagship project (http://www.interomics.eu/it/home), National Research Council CUP Grant B91J12000190001, and the project grant SysBioNet, Italian Roadmap Research Infrastructures 2012. A.C., G.O., and X.C. were supported by grants from NCI R01CA200987, R01CA158472, and U24CA210954. E.P.{\textquoteright}s group is supported by grants from LEO Foundation (grant number LF17006), the Innovation Fund Denmark (grant number 5189-00052B), and the Danish National Research Foundation (DNRF125). Publisher Copyright: {\textcopyright} 2020, The Author(s).",

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AU - Colaprico, Antonio

AU - Olsen, Catharina

AU - Bailey, Matthew H.

AU - Odom, Gabriel J.

AU - Terkelsen, Thilde

AU - Silva, Tiago C.

AU - Olsen, André V.

AU - Cantini, Laura

AU - Zinovyev, Andrei

AU - Barillot, Emmanuel

AU - Noushmehr, Houtan

AU - Bertoli, Gloria

AU - Castiglioni, Isabella

AU - Cava, Claudia

AU - Bontempi, Gianluca

AU - Chen, Xi Steven

AU - Papaleo, Elena

N1 - Funding Information: We are grateful to Matthieu Defrance, Kridsadakorn Chaichoompu, Kristel Van Steen, Benjamin Haibe-Kains ans Thuc Duy Le for suggestions and scientific advice in the Moonlight project. We would also like to thank Lisa Cantwell for her scientific proofreading of the paper. The project was supported by the BridgeIRIS project [http://mlg. ulb.ac.be/BridgeIRIS], funded by INNOVIRIS, Region de Bruxelles Capitale, Brussels, Belgium, and by GENGISCAN: GENomic profiling of Gastrointestinal Inflammatory-Sensitive CANcers, [http://mlg.ulb.ac.be/GENGISCAN] Belgian FNRS PDR (T100914F to A.C., C.O., and Gi.B.). Gi.B. was also supported by the project WALINNOV 2017 – N° 1710030 - CAUSEL I.C, C.C. and Gl.B. were supported by INTEROMICS flagship project (http://www.interomics.eu/it/home), National Research Council CUP Grant B91J12000190001, and the project grant SysBioNet, Italian Roadmap Research Infrastructures 2012. A.C., G.O., and X.C. were supported by grants from NCI R01CA200987, R01CA158472, and U24CA210954. E.P.’s group is supported by grants from LEO Foundation (grant number LF17006), the Innovation Fund Denmark (grant number 5189-00052B), and the Danish National Research Foundation (DNRF125). Publisher Copyright: © 2020, The Author(s).

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N2 - Cancer driver gene alterations influence cancer development, occurring in oncogenes, tumor suppressors, and dual role genes. Discovering dual role cancer genes is difficult because of their elusive context-dependent behavior. We define oncogenic mediators as genes controlling biological processes. With them, we classify cancer driver genes, unveiling their roles in cancer mechanisms. To this end, we present Moonlight, a tool that incorporates multiple -omics data to identify critical cancer driver genes. With Moonlight, we analyze 8000+ tumor samples from 18 cancer types, discovering 3310 oncogenic mediators, 151 having dual roles. By incorporating additional data (amplification, mutation, DNA methylation, chromatin accessibility), we reveal 1000+ cancer driver genes, corroborating known molecular mechanisms. Additionally, we confirm critical cancer driver genes by analysing cell-line datasets. We discover inactivation of tumor suppressors in intron regions and that tissue type and subtype indicate dual role status. These findings help explain tumor heterogeneity and could guide therapeutic decisions.

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Interpreting pathways to discover cancer driver genes with Moonlight

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