Abstract
PURPOSEThe modern researcher is confronted with hundreds of published methods to interpret genetic variants. There are databases of genes and variants, phenotype-genotype relationships, algorithms that score and rank genes, and in silico variant effect prediction tools. Because variant prioritization is a multifactorial problem, a welcome development in the field has been the emergence of decision support frameworks, which make it easier to integrate multiple resources in an interactive environment. Current decision support frameworks are typically limited by closed proprietary architectures, access to a restricted set of tools, lack of customizability, Web dependencies that expose protected data, or limited scalability.METHODSWe present the Open Custom Ranked Analysis of Variants Toolkit1 (OpenCRAVAT) a new open-source, scalable decision support system for variant and gene prioritization. We have designed the resource catalog to be open and modular to maximize community and developer involvement, and as a result, the catalog is being actively developed and growing every month. Resources made available via the store are well suited for analysis of cancer, as well as Mendelian and complex diseases.RESULTSOpenCRAVAT offers both command-line utility and dynamic graphical user interface, allowing users to install with a single command, easily download tools from an extensive resource catalog, create customized pipelines, and explore results in a richly detailed viewing environment. We present several case studies to illustrate the design of custom workflows to prioritize genes and variants.CONCLUSIONOpenCRAVAT is distinguished from similar tools by its capabilities to access and integrate an unprecedented amount of diverse data resources and computational prediction methods, which span germline, somatic, common, rare, coding, and noncoding variants.
Highlights
Next-generation sequencing technologies have greatly reduced the cost of genome sequencing, increasing the availability of genomic data and the need for methods to evaluate genomic variants
OpenCRAVAT offers both command-line utility and dynamic graphical user interface, allowing users to install with a single command, download tools from an extensive resource catalog, create customized pipelines, and explore results in a richly detailed viewing environment
OpenCRAVAT is distinguished from similar tools by its capabilities to access and integrate an unprecedented amount of diverse data resources and computational prediction methods, which span germline, somatic, common, rare, coding, and noncoding variants
Summary
Next-generation sequencing technologies have greatly reduced the cost of genome sequencing, increasing the availability of genomic data and the need for methods to evaluate genomic variants. There is a need for more effective, user-friendly genome analysis tools that include interdisciplinary annotations and resources to suit the needs of both novices and bioinformatics experts. Informative variant and gene characteristics are distributed across thousands of published works, spanning resources from the medical, biologic, and bioinformatics domains, including experimental assays, computational variant effect prediction, evolutionary context, population databases, and established pharmacologic relevance. This abundance of variant and gene annotations challenges researchers to broadly discover and deploy the best resources, as well as incorporate them within custom annotation pipelines. Databases that host precomputes, such as dbNSFP (database for nonsynonymous single-nucleotide polymorphisms’ functional predictions),[2,3] have been instrumental in CONTEXT
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