wANNOVAR: Annotating Genetic Variants for Personal Genomes
wANNOVAR: Annotating Genetic Variants for Personal Genomes
Background High-throughput DNA sequencing platforms have become widely available. As a result, personal genomes are increasingly being sequenced in research and clinical settings. However, the resulting massive amounts of variants data pose significant challenges to the average biologists and clinicians without bioinformatics skills.
Methods and results We developed a web server called wANNOVAR to address the critical needs for functional annotation of genetic variants from personal genomes. The server provides simple and intuitive interface to help users determine the functional significance of variants. These include annotating single nucleotide variants and insertions/deletions for their effects on genes, reporting their conservation levels (such as PhyloP and GERP++ scores), calculating their predicted functional importance scores (such as SIFT and PolyPhen scores), retrieving allele frequencies in public databases (such as the 1000 Genomes Project and NHLBI-ESP 5400 exomes), and implementing a 'variants reduction' protocol to identify a subset of potentially deleterious variants/genes. We illustrated how wANNOVAR can help draw biological insights from sequencing data, by analysing genetic variants generated on two Mendelian diseases.
Conclusions We conclude that wANNOVAR will help biologists and clinicians take advantage of the personal genome information to expedite scientific discoveries. The wANNOVAR server is available at http://wannovar.usc.edu, and will be continuously updated to reflect the latest annotation information.
Over the past 5 years, massively parallel DNA sequencing platforms have become widely available. As a result, variants data on genomes from healthy subjects and patients are being generated at an unprecedented rate. However, the development of bioinformatics tools for handling these data lags behind, creating a gap between the generation of massive data and the ability to fully exploit the biological contents of these data. To fill the urgent demand, we previously developed the ANNOVAR (ANNOtate VARiation) software for functional annotation of genetic variants from sequence data. ANNOVAR efficiently uses up-to-date information to annotate genetic variants detected from diverse genomes with user-specified versions of genome builds. Although ANNOVAR has become one of the most widely used annotation tools for sequencing data, the requirement to type command line arguments makes ANNOVAR inaccessible to the average biologists and clinicians who would otherwise benefit from its extensive functionality.
Therefore, we developed a web server called wANNOVAR to facilitate web-based personal genome annotation, using ANNOVAR as the back-end annotation engine. Users need to simply submit a list of variants (even whole-exome or whole-genome variants), and wANNOVAR can process the submission and generate HTML-based result pages. It allows flexibility by permitting the users to select customised filtering criteria and identify a subset of prioritised variants from thousands or even millions of input variants. Below, we describe the implementation of the wANNOVAR sever and illustrate its utility using two high-throughput sequencing data sets on Mendelian diseases.
Abstract and Introduction
Abstract
Background High-throughput DNA sequencing platforms have become widely available. As a result, personal genomes are increasingly being sequenced in research and clinical settings. However, the resulting massive amounts of variants data pose significant challenges to the average biologists and clinicians without bioinformatics skills.
Methods and results We developed a web server called wANNOVAR to address the critical needs for functional annotation of genetic variants from personal genomes. The server provides simple and intuitive interface to help users determine the functional significance of variants. These include annotating single nucleotide variants and insertions/deletions for their effects on genes, reporting their conservation levels (such as PhyloP and GERP++ scores), calculating their predicted functional importance scores (such as SIFT and PolyPhen scores), retrieving allele frequencies in public databases (such as the 1000 Genomes Project and NHLBI-ESP 5400 exomes), and implementing a 'variants reduction' protocol to identify a subset of potentially deleterious variants/genes. We illustrated how wANNOVAR can help draw biological insights from sequencing data, by analysing genetic variants generated on two Mendelian diseases.
Conclusions We conclude that wANNOVAR will help biologists and clinicians take advantage of the personal genome information to expedite scientific discoveries. The wANNOVAR server is available at http://wannovar.usc.edu, and will be continuously updated to reflect the latest annotation information.
Introduction
Over the past 5 years, massively parallel DNA sequencing platforms have become widely available. As a result, variants data on genomes from healthy subjects and patients are being generated at an unprecedented rate. However, the development of bioinformatics tools for handling these data lags behind, creating a gap between the generation of massive data and the ability to fully exploit the biological contents of these data. To fill the urgent demand, we previously developed the ANNOVAR (ANNOtate VARiation) software for functional annotation of genetic variants from sequence data. ANNOVAR efficiently uses up-to-date information to annotate genetic variants detected from diverse genomes with user-specified versions of genome builds. Although ANNOVAR has become one of the most widely used annotation tools for sequencing data, the requirement to type command line arguments makes ANNOVAR inaccessible to the average biologists and clinicians who would otherwise benefit from its extensive functionality.
Therefore, we developed a web server called wANNOVAR to facilitate web-based personal genome annotation, using ANNOVAR as the back-end annotation engine. Users need to simply submit a list of variants (even whole-exome or whole-genome variants), and wANNOVAR can process the submission and generate HTML-based result pages. It allows flexibility by permitting the users to select customised filtering criteria and identify a subset of prioritised variants from thousands or even millions of input variants. Below, we describe the implementation of the wANNOVAR sever and illustrate its utility using two high-throughput sequencing data sets on Mendelian diseases.