Abstract:
BACKGROUND:Whole exome sequencing studies identify hundreds to thousands of rare protein coding variants of ambiguous significance for human health. Computational tools are needed to accelerate the identification of specific variants and genes that contribute to human disease. RESULTS:We have developed the Variant Effect Scoring Tool (VEST), a supervised machine learning-based classifier, to prioritize rare missense variants with likely involvement in human disease. The VEST classifier training set comprised ~ 45,000 disease mutations from the latest Human Gene Mutation Database release and another ~45,000 high frequency (allele frequency >1%) putatively neutral missense variants from the Exome Sequencing Project. VEST outperforms some of the most popular methods for prioritizing missense variants in carefully designed holdout benchmarking experiments (VEST ROC AUC = 0.91, PolyPhen2 ROC AUC = 0.86, SIFT4.0 ROC AUC = 0.84). VEST estimates variant score p-values against a null distribution of VEST scores for neutral variants not included in the VEST training set. These p-values can be aggregated at the gene level across multiple disease exomes to rank genes for probable disease involvement. We tested the ability of an aggregate VEST gene score to identify candidate Mendelian disease genes, based on whole-exome sequencing of a small number of disease cases. We used whole-exome data for two Mendelian disorders for which the causal gene is known. Considering only genes that contained variants in all cases, the VEST gene score ranked dihydroorotate dehydrogenase (DHODH) number 2 of 2253 genes in four cases of Miller syndrome, and myosin-3 (MYH3) number 2 of 2313 genes in three cases of Freeman Sheldon syndrome. CONCLUSIONS:Our results demonstrate the potential power gain of aggregating bioinformatics variant scores into gene-level scores and the general utility of bioinformatics in assisting the search for disease genes in large-scale exome sequencing studies. VEST is available as a stand-alone software package at http://wiki.chasmsoftware.org and is hosted by the CRAVAT web server at http://www.cravat.us.
journal_name
BMC Genomicsjournal_title
BMC genomicsauthors
Carter H,Douville C,Stenson PD,Cooper DN,Karchin Rdoi
10.1186/1471-2164-14-S3-S3subject
Has Abstractpub_date
2013-01-01 00:00:00pages
S3issn
1471-2164pii
1471-2164-14-S3-S3journal_volume
14 Suppl 3pub_type
杂志文章相关文献
BMC GENOMICS文献大全abstract:BACKGROUND:Photorhabdus luminescens is an enteric bacterium, which lives in mutualistic association with soil nematodes and is highly pathogenic for a broad spectrum of insects. A complete genome sequence for the type strain P. luminescens subsp. laumondii TT01, which was originally isolated in Trinidad and Tobago, has...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-018-5121-z
更新日期:2018-11-29 00:00:00
abstract:BACKGROUND:Cryptocaryon irritans is an obligate parasitic ciliate protozoan that can infect various commercially important mariculture fish species and cause high lethality and economic loss. Current methods of controlling this parasite with chemicals or antibiotics are widely considered to be environmentally harmful. ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-018-4565-5
更新日期:2018-03-12 00:00:00
abstract:BACKGROUND:The siRNA and piRNA pathways have been shown in insects to be essential for regulation of gene expression and defence against exogenous and endogenous genetic elements (viruses and transposable elements). The vast majority of endogenous small RNAs produced by the siRNA and piRNA pathways originate from repet...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-015-1436-1
更新日期:2015-04-10 00:00:00
abstract:BACKGROUND:Microarray technology is limited to monitoring the expression of previously annotated genes that have corresponding probes on the array. Computationally annotated genes have not fully been validated, because ESTs and full-length cDNAs cannot cover entire transcribed regions. Here, mRNA-Seq (an Illumina cDNA ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-11-683
更新日期:2010-12-02 00:00:00
abstract:BACKGROUND:Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from t...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-11-365
更新日期:2010-06-09 00:00:00
abstract:BACKGROUND:Sterol esterases and lipases are enzymes able to efficiently catalyze synthesis and hydrolysis reactions of both sterol esters and triglycerides and due to their versatility could be widely used in different industrial applications. Lipases with this ability have been reported in the yeast Candida rugosa tha...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-14-712
更新日期:2013-10-18 00:00:00
abstract:BACKGROUND:The process of alternative splicing provides a unique mechanism by which eukaryotes are able to produce numerous protein products from the same gene. Heightened variability in the proteome has been thought to potentiate increased behavioral complexity and response flexibility to environmental stimuli, thus c...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-020-6600-6
更新日期:2020-03-23 00:00:00
abstract:BACKGROUND:Thoroughbred horses are the most expensive domestic animals, and their running ability and knowledge about their muscle-related diseases are important in animal genetics. While the horse reference genome is available, there has been no large-scale functional annotation of the genome using expressed genes der...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-13-473
更新日期:2012-09-12 00:00:00
abstract:BACKGROUND:Crustacean moulting is a complex process involving many regulatory pathways. A holistic approach to examine differential gene expression profiles of transcripts relevant to the moulting process, across all moult cycle stages, was used in this study. Custom cDNA microarrays were constructed for Portunus pelag...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-12-147
更新日期:2011-03-12 00:00:00
abstract:BACKGROUND:Fistular leaves frequently appear in Allium species, and previous developmental studies have proposed that the process of fistular leaf formation involves programmed cell death. However, molecular evidence for the role of programmed cell death in the formation of fistular leaf cavities has yet to be reported...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-016-3474-8
更新日期:2017-01-10 00:00:00
abstract:BACKGROUND:The ubiquitin-conjugating enzyme HR6B is required for spermatogenesis in mouse. Loss of HR6B results in aberrant histone modification patterns on the trancriptionally silenced X and Y chromosomes (XY body) and on centromeric chromatin in meiotic prophase. We studied the relationship between these chromatin m...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-11-367
更新日期:2010-06-10 00:00:00
abstract:BACKGROUND:The overwhelming amount of network data in functional genomics is making its visualization cluttered with jumbling nodes and edges. Such cluttered network visualization, which is known as "hair-balls", is significantly hindering data interpretation and analysis of researchers. Effective navigation approaches...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-13-S7-S24
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:A composite biological structure, such as an insect head or abdomen, contains many internal structures with distinct functions. Composite structures are often used in RNA-seq studies, though it is unclear how expression of the same gene in different tissues and structures within the same structure affects th...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-14-586
更新日期:2013-08-28 00:00:00
abstract:BACKGROUND:Carboxylesterase is a multifunctional superfamily and ubiquitous in all living organisms, including animals, plants, insects, and microbes. It plays important roles in xenobiotic detoxification, and pheromone degradation, neurogenesis and regulating development. Previous studies mainly used Dipteran Drosophi...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-10-553
更新日期:2009-11-24 00:00:00
abstract:BACKGROUND:Every year, substantial crop loss occurs globally, as a result of bacterial, fungal, parasite and viral infections in rice. Here, we present an in-depth investigation of the transcriptomic response to infection with the destructive bacterial pathogen Xanthomonas oryzae pv. oryzae(Xoo) in both resistant and s...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-14-93
更新日期:2013-02-12 00:00:00
abstract:BACKGROUND:The ability to rapidly map millions of oligonucleotide fragments to a reference genome is crucial to many high throughput genomic technologies. RESULTS:We propose an intuitive and efficient algorithm, titled extreme MApping of OligoNucleotide (xMAN), to rapidly map millions of oligonucleotide fragments to a...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-9-S1-S20
更新日期:2008-01-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via the original article. ...
journal_title:BMC genomics
pub_type: 杂志文章,已发布勘误
doi:10.1186/s12864-020-06939-7
更新日期:2020-08-11 00:00:00
abstract:BACKGROUND:Gene expression profiling studies of mastitis in ruminants have provided key but fragmented knowledge for the understanding of the disease. A systematic combination of different expression profiling studies via meta-analysis techniques has the potential to test the extensibility of conclusions based on singl...
journal_title:BMC genomics
pub_type: 杂志文章,meta分析
doi:10.1186/1471-2164-12-225
更新日期:2011-05-11 00:00:00
abstract:BACKGROUND:CRISPR is a microbial immune system likely to be involved in host-parasite coevolution. It functions using target sequences encoded by the bacterial genome, which interfere with invading nucleic acids using a homology-dependent system. The system also requires protospacer associated motifs (PAMs), short moti...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-15-663
更新日期:2014-08-08 00:00:00
abstract:BACKGROUND:Dictyostelium discoideum is frequently subjected to environmental changes in its natural habitat, the forest soil. In order to survive, the organism had to develop effective mechanisms to sense and respond to such changes. When cells are faced with a hypertonic environment a complex response is triggered. It...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-8-123
更新日期:2007-05-21 00:00:00
abstract:BACKGROUND:One of the most common and recurrent vaginal infections is bacterial vaginosis (BV). The diagnosis is based on changes to the "normal" vaginal microbiome; however, the normal microbiome appears to differ according to reproductive status and ethnicity, and even among individuals within these groups. The Amsel...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-018-5284-7
更新日期:2018-12-31 00:00:00
abstract:BACKGROUND:Animals are thought to achieve lignocellulose digestion via symbiotic associations with gut microbes; this view leads to significant focus on bacteria and fungi for lignocellulolytic systems. The presence of biomass conversion systems hardwired into animal genomes has not yet been unequivocally demonstrated....
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-018-4861-0
更新日期:2018-06-20 00:00:00
abstract:BACKGROUND:Metagenomic sequencing is a powerful technology for studying the mixture of microbes or the microbiomes on human and in the environment. One basic task of analyzing metagenomic data is to identify the component genomes in the community. This task is challenging due to the complexity of microbiome composition...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-019-5467-x
更新日期:2019-04-04 00:00:00
abstract:BACKGROUND:The relationships between parasitoids and their insect hosts have attracted attention at two levels. First, the basic biology of host-parasitoid interactions is of fundamental interest. Second, parasitoids are widely used as biological control agents in sustainable agricultural programs. Females of the grega...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-11-484
更新日期:2010-09-02 00:00:00
abstract:BACKGROUND:Multidrug- (MDR) and extensively drug resistant (XDR) tuberculosis (TB) presents a challenge to disease control and elimination goals. In Lisbon, Portugal, specific and successful XDR-TB strains have been found in circulation for almost two decades. RESULTS:In the present study we have genotyped and sequenc...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-15-991
更新日期:2014-11-18 00:00:00
abstract:BACKGROUND:Enterohemorrhagic Escherichia coli (EHEC) are zoonotic agents associated with outbreaks worldwide. Growth of EHEC strains in ground beef could be inhibited by background microbiota that is present initially at levels greater than that of the pathogen E. coli. However, how the microbiota outcompetes the patho...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-017-3957-2
更新日期:2017-08-03 00:00:00
abstract:BACKGROUND:Evolution leaves an imprint in species through genetic change. At the molecular level, evolutionary changes can be explored by studying ratios of nucleotide substitutions. The interplay among molecular evolution, derived phenotypes, and ecological ranges can provide insights into adaptive radiations. Caecili...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-019-5694-1
更新日期:2019-05-09 00:00:00
abstract:BACKGROUND:Plant nucleotide-binding site (NBS)-leucine-rich repeat (LRR) proteins encoded by resistance genes play an important role in the responses of plants to various pathogens, including viruses, bacteria, fungi, and nematodes. In this study, a comprehensive analysis of NBS-encoding genes within the whole cucumber...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/1471-2164-14-109
更新日期:2013-02-19 00:00:00
abstract:BACKGROUND:An efficient signal transduction system allows a bacterium to sense environmental cues and then to respond positively or negatively to those signals; this process is referred to as taxis. In addition to external cues, the internal metabolic state of any bacterium plays a major role in determining its ability...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-018-5151-6
更新日期:2018-10-19 00:00:00
abstract:BACKGROUND:Rainbow trout is a significant fish farming species under temperate climates. Female reproduction traits play an important role in the economy of breeding companies with the sale of fertilized eggs. The objectives of this study are threefold: to estimate the genetic parameters of female reproduction traits, ...
journal_title:BMC genomics
pub_type: 杂志文章
doi:10.1186/s12864-020-06955-7
更新日期:2020-08-14 00:00:00