Current variant discovery approaches often rely on an initial read mapping to the reference sequence. Their effectiveness is limited by the presence of gaps, potential misassemblies, regions of duplicates with a high-sequence similarity and regions of high-sequence divergence in the reference. Also, mapping-based approaches are less sensitive to large INDELs and complex variations and provide little phase information in personal genomes. A few de novo assemblers have been developed to identify variants through direct variant calling from the assembly graph, micro-assembly and whole-genome assembly, but mainly for whole-genome sequencing (WGS) data. We developed SGVar, a de novo assembly workflow for haplotype-based variant discovery from whole-exome sequencing (WES) data. Using simulated human exome data, we compared SGVar with five variation-aware de novo assemblers and with BWA-MEM together with three haplotype- or local de novo assembly-based callers. SGVar outperforms the other assemblers in sensitivity and tolerance of sequencing errors. We recapitulated the findings on whole-genome and exome data from a Utah residents with Northern and Western European ancestry (CEU) trio, showing that SGVar had high sensitivity both in the highly divergent human leukocyte antigen (HLA) region and in non-HLA regions of chromosome 6. In particular, SGVar is robust to sequencing error, k-mer selection, divergence level and coverage depth. Unlike mapping-based approaches, SGVar is capable of resolving long-range phase and identifying large INDELs from WES, more prominently from WGS. We conclude that SGVar represents an ideal platform for WES-based variant discovery in highly divergent regions and across the whole genome.
Pubmed ID: 28407084 RIS Download
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Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.
View all literature mentionsSoftware package with functions that will help researchers plan how many subjects per group need to be included in an MRI-based cortical thickness study to ensure a thickness difference is detected. The package requires cortical thickness mapping and co-registration to be carried out using Freesurfer. The power analyses are implemented in the R software package.
View all literature mentionsA dataset containing the full genomic sequence of 1,700 individuals, freely available for research use. The 1000 Genomes Project is an international research effort coordinated by a consortium of 75 companies and organizations to establish the most detailed catalogue of human genetic variation. The project has grown to 200 terabytes of genomic data including DNA sequenced from more than 1,700 individuals that researchers can now access on AWS for use in disease research free of charge. The dataset containing the full genomic sequence of 1,700 individuals is now available to all via Amazon S3. The data can be found at: http://s3.amazonaws.com/1000genomes The 1000 Genomes Project aims to include the genomes of more than 2,662 individuals from 26 populations around the world, and the NIH will continue to add the remaining genome samples to the data collection this year. Public Data Sets on AWS provide a centralized repository of public data hosted on Amazon Simple Storage Service (Amazon S3). The data can be seamlessly accessed from AWS services such Amazon Elastic Compute Cloud (Amazon EC2) and Amazon Elastic MapReduce (Amazon EMR), which provide organizations with the highly scalable compute resources needed to take advantage of these large data collections. AWS is storing the public data sets at no charge to the community. Researchers pay only for the additional AWS resources they need for further processing or analysis of the data. All 200 TB of the latest 1000 Genomes Project data is available in a publicly available Amazon S3 bucket. You can access the data via simple HTTP requests, or take advantage of the AWS SDKs in languages such as Ruby, Java, Python, .NET and PHP. Researchers can use the Amazon EC2 utility computing service to dive into this data without the usual capital investment required to work with data at this scale. AWS also provides a number of orchestration and automation services to help teams make their research available to others to remix and reuse. Making the data available via a bucket in Amazon S3 also means that customers can crunch the information using Hadoop via Amazon Elastic MapReduce, and take advantage of the growing collection of tools for running bioinformatics job flows, such as CloudBurst and Crossbow.
View all literature mentionsA Bayesian genetic variant detector designed to find small polymorphisms, specifically SNPs, indels, MNPs, and complex events smaller than the length of a short-read sequencing alignment.
View all literature mentionsCell line GM12878 is a Transformed cell line with a species of origin Homo sapiens (Human)
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