Bystro: rapid online variant annotation and natural-language filtering at whole-genome scale

Kotlar, Alex V.; Trevino, Cristina E.; Zwick, Michael E.; Cutler, David J.; Wingo, Thomas S.

doi:10.1101/146514

Cited by 18 publications

(20 citation statements)

References 21 publications

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“…All biallelic variants with a genotyping rate of 90% or greater, regardless of MAF, were investigated within each region of interest (defined as 1Mb centered on each lead variant). Each interval was annotated for possible roles in craniofacial development by literature searches of all genes contained within that interval, functional annotation of variants using multiple tools including Bystro (39), Variant Effect Predictor (40), and HaploReg (41). We also queried the UCSC genome browser’s gene-by-gene interaction track for known OFC genes/regions.…”

Section: Methodsmentioning

confidence: 99%

Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21

Mukhopadhyay

Bishop

Mortillo

et al. 2019

Preprint

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51 Orofacial clefts (OFCs) are one of the most common birth defects worldwide and create a 52 significant health burden. The majority of OFCs are non-syndromic, and the genetic component 53 has been only partially determined. Here, we analyze whole genome sequence (WGS) data for 54 association with risk of OFCs in European and Colombian families selected from a multicenter 55 family-based OFC study. Part of the Gabriella Miller Kids First Pediatric Research Program, this 56 is the first large-scale WGS study of OFC in parent-offspring trios. WGS provides deeper and 57 more specific genetic data than currently available using imputation on single nucleotide 58 polymorphic (SNP) marker panels. Here, association analysis of genome-wide single nucleotide 59 variants (SNV) and short insertions and deletions (indels) identified a new locus on chromosome 60 21 in Colombian families, within a region known to be expressed during craniofacial 61 development. This study reinforces the ancestry differences seen in the genetic etiology of OFCs, 62 and the need for larger samples when for studying OFCs and other birth defects in admixed 63 populations. 64

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Section: Methodsmentioning

confidence: 99%

Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21

Mukhopadhyay

Bishop

Mortillo

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…(28) These unique variants were functionally annotated using Bystro (https://bystro.io/) and ANNOVAR, which report the variant's type, functional classification (nonsense, replacement, silent, 5′ or 3′ untranslated region, splice junction, or other intronic, intergenic), presence in the Single Nucleotide Polymorphism Database, and measures of evolutionary conservation. (29,30) To explore the potential contribution of ciliary dysgenesis and/or dysfunction underlying the BASM phenotype, we used a prespecified list of 2,016 genes of interest (GOI; Supporting Table S1) derived principally from two large comprehensive data sets dedicated to ciliomic studies as well as the Emory Genetics Laboratory Ciliopathies Sequencing Panel and Neonatal and Adult Cholestasis Sequencing Panel and a collated list of putative BA candidate susceptibility genes reported in the literature (18,23,27,31) (Fig. 1).…”

Section: Wes and Data Analysesmentioning

confidence: 99%

Identification of Polycystic Kidney Disease 1 Like 1 Gene Variants in Children With Biliary Atresia Splenic Malformation Syndrome

Berauer¹,

Mezina²,

Okou³

et al. 2019

Hepatology

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Biliary atresia (BA) is the most common cause of end‐stage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations—a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole‐exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patient–parent trios, from the National Institute of Diabetes and Digestive and Kidney Diseases–supported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a prespecified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious biallelic variants in polycystic kidney disease 1 like 1 (PKD1L1), a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice, and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other noncholestatic diseases. Conclusion: WES identified biallelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN data set; the dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a biologically plausible, cholangiocyte‐expressed candidate gene for the BASM syndrome.

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“…Annotation of the multi-sample VCF (n=1,196) was performed using Bystro (19) and supplemented by the Broad's ChromHMM annotation of dPFC tissue (20,21). A total of 1,133 samples passed all quality control measures and 63 samples were excluded for one or more of the following reasons.…”

Section: Genetic Datamentioning

confidence: 99%

Genetic control of the human brain proteome

Robins

Wingo

Fan

et al. 2019

Preprint

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Alteration of protein abundance and conformation are widely believed to be the hallmark of neurodegenerative diseases. Yet relatively little is known about the genetic variation that controls protein abundance in the healthy human brain. The genetic control of protein abundance is generally thought to parallel that of RNA expression, but there is little direct evidence to support this view. Here, we performed a large-scale protein quantitative trait locus (pQTL) analysis using single nucleotide variants (SNVs) from whole-genome sequencing and tandem mass spectrometry-based proteomic quantification of 12,691 unique proteins (7,901 after quality control) from the dorsolateral prefrontal cortex (dPFC) in 144 cognitively normal individuals. We identified 28,211 pQTLs that were significantly associated with the abundance of 864 proteins. These pQTLs were compared to dPFC expression quantitative trait loci (eQTL) in cognitive normal individuals (n=169; 81 had protein data) and a meta-analysis of dPFC eQTLs (n=1,433). We found that strong pQTLs are generally only weak eQTLs, and that the majority of strong eQTLs are not detectable pQTLs. These results suggest that the genetic control of mRNA and protein abundance may be substantially distinct and suggests inference concerning protein abundance made from mRNA in human brain should be treated with caution.

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Bystro: rapid online variant annotation and natural-language filtering at whole-genome scale

Abstract: 21Accurately selecting relevant alleles in large sequencing experiments remains

Cited by 18 publications

References 21 publications

Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21

Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21

Identification of Polycystic Kidney Disease 1 Like 1 Gene Variants in Children With Biliary Atresia Splenic Malformation Syndrome

Genetic control of the human brain proteome

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