Genome Nexus: A Comprehensive Resource for the Annotation and Interpretation of Genomic Variants in Cancer

被引：6

作者：

de Bruijn, Ino ^{[1
,2
]}

Li, Xiang ^{[1
]}

Sumer, Selcuk Onur ^{[1
]}

Gross, Benjamin ^{[1
]}

Sheridan, Robert ^{[1
]}

Ochoa, Angelica ^{[1
]}

Wilson, Manda ^{[1
]}

Wang, Avery ^{[1
]}

Zhang, Hongxin ^{[1
]}

Lisman, Aaron ^{[1
]}

Abeshouse, Adam ^{[1
]}

Zhang, Emily ^{[1
,3
]}

Thum, Alice ^{[1
,4
]}

Sadagopan, Ananthan ^{[5
]}

Heins, Zachary ^{[1
,6
]}

Kandoth, Cyriac ^{[1
,7
]}

Rodenburg, Sander ^{[8
]}

Tan, Sander ^{[8
,9
]}

Lukasse, Pieter ^{[8
]}

van Hagen, Sjoerd ^{[8
]}

Fijneman, Remond J. A. ^{[2
]}

Meijer, Gerrit A. ^{[2
]}

Schultz, Nikolaus ^{[1
,10
,11
]}

Gao, Jianjiong ^{[1
,10
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Marie Josee & Henry R Kravis Ctr Mol Oncol, New York, NY 10065 USA

[2] Netherlands Canc Inst, Dept Pathol, Amsterdam, Netherlands

[3] Cornell Univ, Ithaca, NY USA

[4] MongoDB, New York, NY USA

[5] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[6] Boston Univ, Boston, MA 02215 USA

[7] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA

[8] Hyve, Utrecht, Netherlands

[9] Univ Med Ctr Utrecht, Directie Informatie Technol, Utrecht, Netherlands

[10] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Computat Oncol, 1275 York Ave, New York, NY 10065 USA

[11] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

来源：

JCO CLINICAL CANCER INFORMATICS | 2022年 / 6卷

关键词：

PROTEIN; GENE;

D O I：

10.1200/CCI.21.00144

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE Interpretation of genomic variants in tumor samples still presents a challenge in research and the clinical setting. A major issue is that information for variant interpretation is fragmented across disparate databases, and aggregation of information from these requires building extensive infrastructure. To this end, we have developed Genome Nexus, a one-stop shop for variant annotation with a user-friendly interface for cancer researchers and clinicians. METHODS Genome Nexus (1) aggregates variant information from sources that are relevant to cancer research and clinical applications, (2) allows high-performance programmatic access to the aggregated data via a unified application programming interface, (3) provides a reference page for individual cancer variants, (4) provides user-friendly tools for annotating variants in patients, and (5) is freely available under an open source license and can be installed in a private cloud or local environment and integrated with local institutional resources. RESULTS Genome Nexus is available at https://www.genomenexus.org. It displays annotations from more than a dozen resources including those that provide variant effect information (variant effect predictor), protein sequence annotation (Uniprot, Pfam, and dbPTM), functional consequence prediction (Polyphen-2, Mutation Assessor, and SIFT), population prevalences (gnomAD, dbSNP, and ExAC), cancer population prevalences (Cancer hotspots and SignalDB), and clinical actionability (OncoKB, CIViC, and ClinVar). We describe several use cases that demonstrate the utility of Genome Nexus to clinicians, researchers, and bioinformaticians. We cover single-variant annotation, cohort analysis, and programmatic use of the application programming interface. Genome Nexus is unique in providing a user-friendly interface specific to cancer that allows highperformance annotation of any variant including unknown ones. CONCLUSION Interpretation of cancer genomic variants is improved tremendously by having an integrated resource for annotations. Genome Nexus is freely available under an open source license. (C) 2022 by American Society of Clinical Oncology

引用

页数：11

共 35 条

[11] Glycogen synthase kinase 3β regulates cyclin D1 proteolysis and subcellular localization [J].

Diehl, JA ;

Cheng, MG ;

Roussel, MF ;

Sherr, CJ .

GENES & DEVELOPMENT, 1998, 12 (22) :3499-3511

[12] CRAVAT: cancer-related analysis of variants toolkit [J].

Douville, Christopher ;

Carter, Hannah ;

Kim, Rick ;

Niknafs, Noushin ;

Diekhans, Mark ;

Stenson, Peter D. ;

Cooper, David N. ;

Ryan, Michael ;

Karchin, Rachel .

BIOINFORMATICS, 2013, 29 (05) :647-648

[13] COSMIC: exploring the world's knowledge of somatic mutations in human cancer [J].

Forbes, Simon A. ;

Beare, David ;

Gunasekaran, Prasad ;

Leung, Kenric ;

Bindal, Nidhi ;

Boutselakis, Harry ;

Ding, Minjie ;

Bamford, Sally ;

Cole, Charlotte ;

Ward, Sari ;

Kok, Chai Yin ;

Jia, Mingming ;

De, Tisham ;

Teague, Jon W. ;

Stratton, Michael R. ;

McDermott, Ultan ;

Campbell, Peter J. .

NUCLEIC ACIDS RESEARCH, 2015, 43 (D1) :D805-D811

[14] 3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets [J].

Gao, Jianjiong ;

Chang, Matthew T. ;

Johnsen, Hannah C. ;

Gao, Sizhi Paul ;

Sylvester, Brooke E. ;

Sumer, Selcuk Onur ;

Zhang, Hongxin ;

Solit, David B. ;

Taylor, Barry S. ;

Schultz, Nikolaus ;

Sander, Chris .

GENOME MEDICINE, 2017, 9

[15] Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal [J].

Gao, Jianjiong ;

Aksoy, Buelent Arman ;

Dogrusoz, Ugur ;

Dresdner, Gideon ;

Gross, Benjamin ;

Sumer, S. Onur ;

Sun, Yichao ;

Jacobsen, Anders ;

Sinha, Rileen ;

Larsson, Erik ;

Cerami, Ethan ;

Sander, Chris ;

Schultz, Nikolaus .

SCIENCE SIGNALING, 2013, 6 (269) :pl1

[16] ClinGen's RASopathy Expert Panel consensus methods for variant interpretation [J].

Gelb, Bruce D. ;

Cave, Helene ;

Dillon, Mitchell W. ;

Gripp, Karen W. ;

Lee, Jennifer A. ;

Mason-Suares, Heather ;

Rauen, Katherine A. ;

Williams, Bradley ;

Zenker, Martin ;

Vincent, Lisa M. .

GENETICS IN MEDICINE, 2018, 20 (11) :1334-1345

[17] CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer [J].

Griffith, Malachi ;

Spies, Nicholas C. ;

Krysiak, Kilannin ;

McMichael, Joshua F. ;

Coffman, Adam C. ;

Danos, Arpad M. ;

Ainscough, Benjamin J. ;

Ramirez, Cody A. ;

Rieke, Damian T. ;

Kujan, Lynzey ;

Barnell, Erica K. ;

Wagner, Alex H. ;

Skidmore, Zachary L. ;

Wollam, Amber ;

Liu, Connor J. ;

Jones, Martin R. ;

Bilski, Rachel L. ;

Lesurf, Robert ;

Feng, Yan-Yang ;

Shah, Nakul M. ;

Bonakdar, Melika ;

Trani, Lee ;

Matlock, Matthew ;

Ramu, Avinash ;

Campbell, Katie M. ;

Spies, Gregory C. ;

Graubert, Aaron P. ;

Gangavarapu, Karthik ;

Eldred, James M. ;

Larson, David E. ;

Walker, Jason R. ;

Good, Benjamin M. ;

Wu, Chunlei ;

Su, Andrew I. ;

Dienstmann, Rodrigo ;

Margolin, Adam A. ;

Tamborero, David ;

Lopez-Bigas, Nuria ;

Jones, Steven J. M. ;

Bose, Ron ;

Spencer, David H. ;

Wartman, Lukas D. ;

Wilson, Richard K. ;

Mardis, Elaine R. ;

Griffith, Obi L. .

NATURE GENETICS, 2017, 49 (02) :170-174

[18] Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer [J].

Hoadley, Katherine A. ;

Yau, Christina ;

Hinoue, Toshinori ;

Wolf, Denise M. ;

Lazar, Alexander J. ;

Drill, Esther ;

Shen, Ronglai ;

Taylor, Alison M. ;

Cherniack, Andrew D. ;

Thorsson, Vesteinn ;

Akbani, Rehan ;

Bowlby, Reanne ;

Wong, Christopher K. ;

Wiznerowicz, Maciej ;

Sanchez-Vega, Francisco ;

Robertson, A. Gordon ;

Schneider, Barbara G. ;

Lawrence, Michael S. ;

Noushmehr, Houtan ;

Malta, Tathiane M. ;

Stuart, Joshua M. ;

Benz, Christopher C. ;

Laird, Peter W. .

CELL, 2018, 173 (02) :291-+

[19] Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm [J].

Kumar, Prateek ;

Henikoff, Steven ;

Ng, Pauline C. .

NATURE PROTOCOLS, 2009, 4 (07) :1073-1082

[20] ClinVar: public archive of interpretations of clinically relevant variants [J].

Landrum, Melissa J. ;

Lee, Jennifer M. ;

Benson, Mark ;

Brown, Garth ;

Chao, Chen ;

Chitipiralla, Shanmuga ;

Gu, Baoshan ;

Hart, Jennifer ;

Hoffman, Douglas ;

Hoover, Jeffrey ;

Jang, Wonhee ;

Katz, Kenneth ;

Ovetsky, Michael ;

Riley, George ;

Sethi, Amanjeev ;

Tully, Ray ;

Villamarin-Salomon, Ricardo ;

Rubinstein, Wendy ;

Maglott, Donna R. .

NUCLEIC ACIDS RESEARCH, 2016, 44 (D1) :D862-D868

← 1 2 3 4 →