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A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders

BACKGROUND: Mendelian disorders are mostly caused by single mutations in the DNA sequence of a gene, leading to a phenotype with pathologic consequences. Whole Exome Sequencing of patients can be a cost-effective alternative to standard genetic screenings to find causative mutations of genetic disea...

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Autores principales: Mutarelli, Margherita, Marwah, Veer Singh, Rispoli, Rossella, Carrella, Diego, Dharmalingam, Gopuraja, Oliva, Gennaro, di Bernardo, Diego
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083405/
https://www.ncbi.nlm.nih.gov/pubmed/25078076
http://dx.doi.org/10.1186/1471-2164-15-S3-S5
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author Mutarelli, Margherita
Marwah, Veer Singh
Rispoli, Rossella
Carrella, Diego
Dharmalingam, Gopuraja
Oliva, Gennaro
di Bernardo, Diego
author_facet Mutarelli, Margherita
Marwah, Veer Singh
Rispoli, Rossella
Carrella, Diego
Dharmalingam, Gopuraja
Oliva, Gennaro
di Bernardo, Diego
author_sort Mutarelli, Margherita
collection PubMed
description BACKGROUND: Mendelian disorders are mostly caused by single mutations in the DNA sequence of a gene, leading to a phenotype with pathologic consequences. Whole Exome Sequencing of patients can be a cost-effective alternative to standard genetic screenings to find causative mutations of genetic diseases, especially when the number of cases is limited. Analyzing exome sequencing data requires specific expertise, high computational resources and a reference variant database to identify pathogenic variants. RESULTS: We developed a database of variations collected from patients with Mendelian disorders, which is automatically populated thanks to an associated exome-sequencing pipeline. The pipeline is able to automatically identify, annotate and store insertions, deletions and mutations in the database. The resource is freely available online http://exome.tigem.it. The exome sequencing pipeline automates the analysis workflow (quality control and read trimming, mapping on reference genome, post-alignment processing, variation calling and annotation) using state-of-the-art software tools. The exome-sequencing pipeline has been designed to run on a computing cluster in order to analyse several samples simultaneously. The detected variants are annotated by the pipeline not only with the standard variant annotations (e.g. allele frequency in the general population, the predicted effect on gene product activity, etc.) but, more importantly, with allele frequencies across samples progressively collected in the database itself, stratified by Mendelian disorder. CONCLUSIONS: We aim at providing a resource for the genetic disease community to automatically analyse whole exome-sequencing samples with a standard and uniform analysis pipeline, thus collecting variant allele frequencies by disorder. This resource may become a valuable tool to help dissecting the genotype underlying the disease phenotype through an improved selection of putative patient-specific causative or phenotype-associated variations.
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spelling pubmed-40834052014-07-18 A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders Mutarelli, Margherita Marwah, Veer Singh Rispoli, Rossella Carrella, Diego Dharmalingam, Gopuraja Oliva, Gennaro di Bernardo, Diego BMC Genomics Research BACKGROUND: Mendelian disorders are mostly caused by single mutations in the DNA sequence of a gene, leading to a phenotype with pathologic consequences. Whole Exome Sequencing of patients can be a cost-effective alternative to standard genetic screenings to find causative mutations of genetic diseases, especially when the number of cases is limited. Analyzing exome sequencing data requires specific expertise, high computational resources and a reference variant database to identify pathogenic variants. RESULTS: We developed a database of variations collected from patients with Mendelian disorders, which is automatically populated thanks to an associated exome-sequencing pipeline. The pipeline is able to automatically identify, annotate and store insertions, deletions and mutations in the database. The resource is freely available online http://exome.tigem.it. The exome sequencing pipeline automates the analysis workflow (quality control and read trimming, mapping on reference genome, post-alignment processing, variation calling and annotation) using state-of-the-art software tools. The exome-sequencing pipeline has been designed to run on a computing cluster in order to analyse several samples simultaneously. The detected variants are annotated by the pipeline not only with the standard variant annotations (e.g. allele frequency in the general population, the predicted effect on gene product activity, etc.) but, more importantly, with allele frequencies across samples progressively collected in the database itself, stratified by Mendelian disorder. CONCLUSIONS: We aim at providing a resource for the genetic disease community to automatically analyse whole exome-sequencing samples with a standard and uniform analysis pipeline, thus collecting variant allele frequencies by disorder. This resource may become a valuable tool to help dissecting the genotype underlying the disease phenotype through an improved selection of putative patient-specific causative or phenotype-associated variations. BioMed Central 2014-05-06 /pmc/articles/PMC4083405/ /pubmed/25078076 http://dx.doi.org/10.1186/1471-2164-15-S3-S5 Text en Copyright © 2014 Mutarelli et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Mutarelli, Margherita
Marwah, Veer Singh
Rispoli, Rossella
Carrella, Diego
Dharmalingam, Gopuraja
Oliva, Gennaro
di Bernardo, Diego
A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders
title A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders
title_full A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders
title_fullStr A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders
title_full_unstemmed A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders
title_short A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders
title_sort community-based resource for automatic exome variant-calling and annotation in mendelian disorders
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083405/
https://www.ncbi.nlm.nih.gov/pubmed/25078076
http://dx.doi.org/10.1186/1471-2164-15-S3-S5
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