title: VarElect: the phenotype-based variation prioritizer of the GeneCards Suite.
abstract: Next generation sequencing (NGS) provides a key technology for deciphering the genetic underpinnings of human diseases. Typical NGS analyses of a patient depict tens of thousands non-reference coding variants, but only one or very few are expected to be significant for the relevant disorder. In a filtering stage, one employs family segregation, rarity in the population, predicted protein impact and evolutionary conservation as a means for shortening the variation list. However, narrowing down further towards culprit disease genes usually entails laborious seeking of gene-phenotype relationships, consulting numerous separate databases. Thus, a major challenge is to transition from the few hundred shortlisted genes to the most viable disease-causing candidates.
  
  
  
  We describe a novel tool, VarElect ( http://ve.genecards.org ), a comprehensive phenotype-dependent variant/gene prioritizer, based on the widely-used GeneCards, which helps rapidly identify causal mutations with extensive evidence. The GeneCards suite offers an effective and speedy alternative, whereby >120 gene-centric automatically-mined data sources are jointly available for the task. VarElect cashes on this wealth of information, as well as on GeneCards' powerful free-text Boolean search and scoring capabilities, proficiently matching variant-containing genes to submitted disease/symptom keywords. The tool also leverages the rich disease and pathway information of MalaCards, the human disease database, and PathCards, the unified pathway (SuperPaths) database, both within the GeneCards Suite. The VarElect algorithm infers direct as well as indirect links between genes and phenotypes, the latter benefitting from GeneCards' diverse gene-to-gene data links in GenesLikeMe. Finally, our tool offers an extensive gene-phenotype evidence portrayal ("MiniCards") and hyperlinks to the parent databases.
  
  
  
  We demonstrate that VarElect compares favorably with several often-used NGS phenotyping tools, thus providing a robust facility for ranking genes, pointing out their likelihood to be related to a patient's disease. VarElect's capacity to automatically process numerous NGS cases, either in stand-alone format or in VCF-analyzer mode (TGex and VarAnnot), is indispensable for emerging clinical projects that involve thousands of whole exome/genome NGS analyses.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.|LifeMap Sciences Ltd, Tel Aviv, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Stelzer
authors.affiliation: LifeMap Sciences Ltd, Tel Aviv, Israel.
authors.forename: Inbar
authors.initials: I
authors.lastname: Plaschkes
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Danit
authors.initials: D
authors.lastname: Oz-Levi
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Alkelai
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Tsviya
authors.initials: T
authors.lastname: Olender
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Shahar
authors.initials: S
authors.lastname: Zimmerman
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Twik
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
authors.forename: Frida
authors.initials: F
authors.lastname: Belinky
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Simon
authors.initials: S
authors.lastname: Fishilevich
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Nudel
authors.affiliation: LifeMap Sciences Inc, Marshfield, MA, 02050, USA.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Guan-Golan
authors.affiliation: LifeMap Sciences Inc, Marshfield, MA, 02050, USA.
authors.forename: David
authors.initials: D
authors.lastname: Warshawsky
authors.affiliation: LifeMap Sciences Ltd, Tel Aviv, Israel.|Toldot Genetics Ltd, Hod Hasharon, Israel.
authors.forename: Dvir
authors.initials: D
authors.lastname: Dahary
authors.affiliation: LifeMap Sciences Inc, Marshfield, MA, 02050, USA.
authors.forename: Asher
authors.initials: A
authors.lastname: Kohn
authors.affiliation: LifeMap Sciences Ltd, Tel Aviv, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Mazor
authors.affiliation: LifeMap Sciences Ltd, Tel Aviv, Israel.
authors.forename: Sergey
authors.initials: S
authors.lastname: Kaplan
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Tsippi
authors.initials: T
authors.lastname: Iny Stein
authors.affiliation: The Genetics Institute, Rambam Health Care Campus, Haifa, Israel.|Rappaport School of Medicine, Technion, Haifa, Israel.
authors.forename: Hagit N
authors.initials: HN
authors.lastname: Baris
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Rappaport
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Safran
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. doron.lancet@weizmann.ac.il.
authors.forename: Doron
authors.initials: D
authors.lastname: Lancet
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D057225:Data Mining; D030541:Databases, Genetic; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D010641:Phenotype
keywords: Gene prioritization; Guilt by association; Next generation sequencing analysis; Phenotype interpretation; Phenotyping; Variant selection