MARRVEL: Integration of human and model organism genetic resources to facilitate functional annotation of the human genome

This article [attached] is a follow-up on today’s theme of “Bioinformatics.” One major challenge encountered with interpreting human genetic variants is our limited understanding of the functional impact of genetic alterations on biological processes. Traditional variant interpretation methodology relies on restricting clinical interpretation to known Mendelian diseases and employing in silico prediction algorithms. For most genes, few variants have reliable and validated clinical significance designation, resulting in difficulties in differentiating between benign and pathogenic variants or determining whether variants in a candidate gene are causative.

The wealth of available biological information across multiple model organisms could aid in the interpretation of variants such as known molecular functions of the candidate gene; however, there are major barriers to searching for biological data in specific model organism databases –– due to the intricacies of evaluating orthologs and navigating seven different websites’ different organization, different approaches, and different use of gene or protein identifiers. This limits the efficiency of incorporating known model organism data into analysis of candidate genes. Hence, there is an unmet demand for resources to facilitate rapid curation of available human gene and variant information, to determine evolutionary conservation, and to gather relevant information on homologous genes in model organisms.

Furthermore, such data compilation is relevant to evaluating the consequences of human genetic variation in model organisms. To provide a concise and user-friendly curation of pertinent and publicly available knowledge, authors [attached article] created MARRVEL (Model organism Aggregated Resources for Rare Variant Exploration). MARRVEL is an open-access resource that integrates and synthesizes genetic and model organism information from several public databases into a single user-friendly website. The information is derived from six human genetic databases and seven model organism databases. For any given variant or gene, MARRVEL displays information from OMIM, ExAC, ClinVar, Geno2MP, DGV, and DECIPHER. MARRVEL also curates model organism-specific databases to concurrently display a concise summary regarding human gene homologs in budding and fission yeast, worm, fly, fish, mouse, and rat on a single webpage.

Experiment-based information on tissue expression, protein subcellular localization, biological processes, and molecular function for the human gene and homologs in the seven model organisms are arranged into a concise output. Thus, rather than visiting multiple separate databases for variant and gene analysis, users can obtain important information –– by searching just one time through MARRVEL. In summary, MARRVEL is able dramatically to improve efficiency and accessibility to data collection and to facilitate analysis of human genes and variants by cross-disciplinary integration of 18 million records available in public databases to facilitate clinical diagnosis and basic research..!! Wow.

Am J Hum Genet 1 June 2o17; 100: 843–853

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