A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer

被引：102

作者：

Wagner, Alex H. ^{[1
]}

Walsh, Brian ^{[2
]}

Mayfield, Georgia ^{[2
]}

Tamborero, David ^{[3
,4
]}

Sonkin, Dmitriy

Krysiak, Kilannin ^{[1
]}

Deu-Pons, Jordi ^{[5
,6
]}

Duren, Ryan P. ^{[7
]}

Gao, Jianjiong ^{[8
]}

McMurry, Julie ^{[2
]}

Patterson, Sara ^{[9
]}

Fitz, Catherine ^{[10
]}

Pitel, Beth A. ^{[11
,12
]}

Sezerman, Ozman U. ^{[12
]}

Ellrott, Kyle ^{[2
]}

Warner, Jeremy L. ^{[13
]}

Rieke, Damian T. ^{[14
]}

Aittokallio, Tero ^{[15
,16
]}

Cerami, Ethan ^{[10
]}

Ritter, Deborah I. ^{[17
,18
]}

Schriml, Lynn M. ^{[19
]}

Freimuth, Robert R. ^{[25
]}

Haendel, Melissa ^{[2
,20
]}

Raca, Gordana ^{[21
,22
]}

Madhavan, Subha ^{[23
]}

Baudis, Michael ^{[24
]}

Beckmann, Jacques S. ^{[25
]}

Dienstmann, Rodrigo ^{[26
]}

Chakravarty, Debyani ^{[8
]}

Li, Xuan Shirley ^{[7
]}

Mockus, Susan ^{[9
]}

Elemento, Olivier ^{[27
]}

Schultz, Nikolaus ^{[8
]}

Lopez-Bigas, Nuria ^{[3
,5
,6
]}

Lawler, Mark ^{[28
]}

Goecks, Jeremy ^{[2
]}

Griffith, Malachi ^{[1
]}

Griffith, Obi L. ^{[1
]}

Margolin, Adam A. ^{[2
]}

机构：

[1] Washington Univ, Sch Med, St Louis, MO 63130 USA

[2] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

[3] Pompeu Fabra Univ, Barcelona, Spain

[4] Karolinska Inst, Solna, Sweden

[5] Inst Res Biomed, Barcelona, Spain

[6] Catalan Inst Res & Adv Studies, Barcelona, Spain

[7] MolecularMatch, Houston, TX USA

[8] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[9] Jackson Lab Genom Med, Farmington, CT USA

[10] Dana Farber Canc Inst, Boston, MA 02115 USA

[11] Mayo Clin, Rochester, MN USA

[12] Acibadem Univ, Istanbul, Turkey

[13] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA

[14] Charite Berlin Univ Med, Berlin, Germany

[15] Inst Mol Med Finland, Helsinki, Finland

[16] Univ Turku, Turku, Finland

[17] Baylor Coll Med, Houston, TX 77030 USA

[18] Texas Childrens Hosp, Houston, TX 77030 USA

[19] Univ Maryland, Sch Med, Baltimore, MD 21201 USA

[20] Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA

[21] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

[22] USC, Keck Sch Med, Los Angeles, CA USA

[23] Georgetown Univ, Med Ctr, Washington, DC 20007 USA

[24] Univ Zurich, Zurich, Switzerland

[25] Univ Lausanne, Lausanne, Switzerland

[26] Vall Hebron Inst Oncol, Barcelona, Spain

[27] Weill Cornell Med, New York, NY USA

[28] Queens Univ Belfast, Belfast, Antrim, North Ireland

来源：

NATURE GENETICS | 2020年 / 52卷 / 04期

基金：

欧洲研究理事会; 英国医学研究理事会; 芬兰科学院;

关键词：

JOINT-CONSENSUS-RECOMMENDATION; SEQUENCE VARIANTS; PRECISION MEDICINE; MUTATIONS; DATABASE; ASSOCIATION; GUIDELINES; STANDARDS; GENETICS; COLLEGE;

D O I：

10.1038/s41588-020-0603-8

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. We demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 57% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide a freely available web interface () for exploring the harmonized interpretations from these six knowledgebases.

引用

页码：448 / +

页数：17

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