GAMES identifies and annotates mutations in next-generation sequencing projects

Sana, Maria Elena; Iascone, Maria; Marchetti, Daniela; Palatini, Jeff; Galasso, Marco; Volinia, Stefano

doi:10.1093/bioinformatics/btq603

Cited by 29 publications

(20 citation statements)

References 38 publications

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“…Moreover, the list of somatic variants can be influenced by the settings used for variant detection and filtering of putative sites. Recently GAMES [14], a new tool useful to identify and annotate mutations in next-generation sequencing was published but it is not implemented for somatic analysis. Further improvements are in progress in our procedure to identify common aberrations in multiple data sets, to introduce functional annotations of SNVs located in intronic and intergenic regions and to combine DNA data analysis with gene expression profiles.…”

Section: Discussionmentioning

confidence: 99%

A Bioinformatics Procedure to Identify and Annotate Somatic Mutations in Whole-Exome Sequencing Data

Spinelli

Pirola

Valletta

et al. 2012

Computational Intelligence Methods for Bioinformatics and Biostatistics

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Abstract. The application of next-generation sequencing instruments generates a tremendous amount of sequencing data. This leads to a challenging bioinformatics problem to store, manage and analyze terabytes of sequencing data often generated from extremely different data-sources. Our project is mainly focused on the sequence analysis of human cancer genomes, in order to identify the genetic lesions underlying the development of tumors. However, the automated detection procedure of somatic mutations and a statistical based testing procedure to identify genetic lesions are still an open problem. Therefore, we propose a computational procedure to manage large scale sequencing data in order to detect exonic somatic mutations in a tumor sample. The proposed pipeline includes several steps based on open-source softwares and R language: alignment, detection of mutations, annotation, functional classification and visualization of results. We analyzed whole exome sequencing data from 3 leukemic patients and 3 paired controls plus 1 colon cancer sample and paired control. The results were validated by Sanger sequencing.

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Section: Discussionmentioning

confidence: 99%

A Bioinformatics Procedure to Identify and Annotate Somatic Mutations in Whole-Exome Sequencing Data

Spinelli

Pirola

Valletta

et al. 2012

Computational Intelligence Methods for Bioinformatics and Biostatistics

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“…However, Perl APIs require a Perl wrapper and queries to remote databases often hinder performance. Another tool called GAMES[39] identifies and annotates SNVs and indels in NGS projects but is currently limited to a single version of the human genome. Similar tools which can offer an improved annotation speed are SeqAnt[40] and AnnoVar[41] which aim at annotating SNVs and indels but provide little annotation information and do not produce any tally.…”

Section: Discussionmentioning

confidence: 99%

Segtor: Rapid Annotation of Genomic Coordinates and Single Nucleotide Variations Using Segment Trees

et al. 2011

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Various research projects often involve determining the relative position of genomic coordinates, intervals, single nucleotide variations (SNVs), insertions, deletions and translocations with respect to genes and their potential impact on protein translation. Due to the tremendous increase in throughput brought by the use of next-generation sequencing, investigators are routinely faced with the need to annotate very large datasets. We present Segtor, a tool to annotate large sets of genomic coordinates, intervals, SNVs, indels and translocations. Our tool uses segment trees built using the start and end coordinates of the genomic features the user wishes to use instead of storing them in a database management system. The software also produces annotation statistics to allow users to visualize how many coordinates were found within various portions of genes. Our system currently can be made to work with any species available on the UCSC Genome Browser. Segtor is a suitable tool for groups, especially those with limited access to programmers or with interest to analyze large amounts of individual genomes, who wish to determine the relative position of very large sets of mapped reads and subsequently annotate observed mutations between the reads and the reference. Segtor (http://lbbc.inca.gov.br/segtor/) is an open-source tool that can be freely downloaded for non-profit use. We also provide a web interface for testing purposes.

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“…Data filtering and analysis were performed using a custom pipeline as previously reported [9, 10]. The set parameters for the variant calling were mapping quality of 20, minimum Phred base quality score of 30 and minimum read depth of 10X.…”

Section: Methodsmentioning

confidence: 99%

A Novel HRAS Mutation Independently Contributes to Left Ventricular Hypertrophy in a Family with a Known MYH7 Mutation

et al. 2016

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Several genetic conditions can lead to left ventricular hypertrophy (LVH). Among them, hypertrophic cardiomyopathy (HCM), caused by mutations in sarcomere genes, is the most common inherited cardiac disease. Instead, RASopathies, a rare class of disorders characterized by neuro-cardio-facial-cutaneous abnormalities and sometimes presenting with LVH, are caused by mutations in the RAS-MAPK pathway. We report on a 62-years-old male who presented isolated severe obstructive LVH but did not carry the sarcomere mutation previously identified in his affected relatives. By exome sequencing, we detected a novel mutation in HRAS gene (NM_005343.2:p.Arg68Trp), present also in the proband’s daughter, who showed mild LVH and severe intellectual disability. The cardiac phenotype was indistinguishable between family members carrying either mutation. In silico studies suggested that the mutated HRAS protein is constitutionally activated. Consistently, functional characterization in vitro confirmed elevated HRAS-GTP accumulation and downstream RAS-MAPK pathway activation that are known to drive cell proliferation in LVH. Our study emphasizes the role of RAS signaling in cardiac hypertrophy and highlights the complexity in differential diagnosis of RASopathies. In fact, the mild features of RASopathy and the recurrence of sarcomeric HCM in this family delayed the correct diagnosis until comprehensive genetic testing was performed.

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GAMES identifies and annotates mutations in next-generation sequencing projects

Abstract: GAMES is available free of charge to academic users and may be obtained from http://aqua.unife.it/GAMES.

Cited by 29 publications

References 38 publications

A Bioinformatics Procedure to Identify and Annotate Somatic Mutations in Whole-Exome Sequencing Data

A Bioinformatics Procedure to Identify and Annotate Somatic Mutations in Whole-Exome Sequencing Data

Segtor: Rapid Annotation of Genomic Coordinates and Single Nucleotide Variations Using Segment Trees

A Novel HRAS Mutation Independently Contributes to Left Ventricular Hypertrophy in a Family with a Known MYH7 Mutation

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