Sentieon DNASeq Variant Calling Workflow Demonstrates Strong Computational Performance and Accuracy

Kendig, Katherine; Baheti, Saurabh; Bockol, Matthew A.; Drucker, Travis; Hart, Steven N.; Heldenbrand, Jacob R; Hernáez, Mikel; Hudson, Matthew E.; Kalmbach, Michael; Klee, Eric W.; Mattson, Nathan R; Roß, Christian; Taschuk, Morgan; Wieben, Eric D.; Wiepert, Mathieu; Wildman, Derek E.; Mainzer, Liudmila Sergeevna

doi:10.3389/fgene.2019.00736

Cited by 177 publications

(135 citation statements)

References 17 publications

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“…com) 46 . Data were processed using a custom version of Sentieon and aligned to GRCh38, with variant calling and phasing algorithms following GATK best practices 47 . Imputation of common variants in the HNP data was performed by pre-phasing samples and then imputing.…”

Section: Methodsmentioning

confidence: 99%

Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts

et al. 2020

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Understanding the impact of rare variants is essential to understanding human health. We analyze rare (MAF < 0.1%) variants against 4264 phenotypes in 49,960 exome-sequenced individuals from the UK Biobank and 1934 phenotypes (1821 overlapping with UK Biobank) in 21,866 members of the Healthy Nevada Project (HNP) cohort who underwent Exome + sequencing at Helix. After using our rare-variant-tailored methodology to reduce test statistic inflation, we identify 64 statistically significant gene-based associations in our meta-analysis of the two cohorts and 37 for phenotypes available in only one cohort. Singletons make significant contributions to our results, and the vast majority of the associations could not have been identified with a genotyping chip. Our results are available for interactive browsing in a webapp (https://ukb.research.helix.com). This comprehensive analysis illustrates the biological value of large, deeply phenotyped cohorts of unselected populations coupled with NGS data.

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Section: Methodsmentioning

confidence: 99%

Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts

et al. 2020

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“…We also sequenced seven accessions with 8-to 160-fold paired-end sequencing using the Illumina HiSeq 2500 platform. Reads were processed and variants were called based on PN40024 (version 12X.v2) 26 using the Sentieon DNA Software Package (version, Golden helix) 53 with default settings. This Sentieon package is a speed-up software that rebuilt the Genome Analysis Toolkit HaplotypeCaller and returns the same result as GATK 3.3.…”

Section: Genus-wide Variant Calling a Total Of 47mentioning

confidence: 99%

Haplotyping the Vitis collinear core genome with rhAmpSeq improves marker transferability in a diverse genus

et al. 2020

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Transferable DNA markers are essential for breeding and genetics. Grapevine (Vitis) breeders utilize disease resistance alleles from congeneric species~20 million years divergent, but existing Vitis marker platforms have cross-species transfer rates as low as 2%. Here, we apply a marker strategy targeting the inferred Vitis core genome. Incorporating seven linkedread de novo assemblies and three existing assemblies, the Vitis collinear core genome is estimated to converge at 39.8 Mb (8.67% of the genome). Adding shotgun genome sequences from 40 accessions enables identification of conserved core PCR primer binding sites flanking polymorphic haplotypes with high information content. From these target regions, we develop 2,000 rhAmpSeq markers as a PCR multiplex and validate the panel in four biparental populations spanning the diversity of the Vitis genus, showing transferability increases to 91.9%. This marker development strategy should be widely applicable for genetic studies in many taxa, particularly those~20 million years divergent.

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“…Bioinformatics analysis. Read mapping and variant calling were performed using Sentieon's DNAseq [48,49] FASTQ to VCF pipeline implemented on the DNAnexus cloud [USA]. Briefly, sequence reads were aligned to the GRCh38 reference genome using the BWA-MEM algorithm [50].…”

Section: Plos Onementioning

confidence: 99%

Genetic landscape of preterm birth due to cervical insufficiency: Comprehensive gene analysis and patient next-generation sequencing data interpretation

et al. 2020

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Preterm delivery is both a traumatizing experience for the patient and a burden on the healthcare system. A condition distinguishable by its phenotype in prematurity is cervical insufficiency, where certain cases exhibit a strong genetic component. Despite genomic advancements, little is known about the genetics of human cervix remodeling during pregnancy. Using selected gene approaches, a few studies have demonstrated an association of common gene variants with cervical insufficiency. However, until now, no study has employed comprehensive methods to investigate this important subject matter. In this study, we asked: i) are there genes reliably linked to cervical insufficiency and, if so, what are their roles? and ii) what is the proportion of cases of non-syndromic cervical insufficiency attributable to these genetic variations? We performed next-generation sequencing on 21 patients with a clinical presentation of cervical insufficiency. To assist the sequencing data interpretation, we retrieved all known genes implicated in cervical functioning through a systematic literature analysis and additional gene searches. These genes were then classified according to their relation to the questions being posed by the study. Patients' sequence variants were filtered for pathogenicity and assigned a likelihood of being contributive to phenotype development. Gene extraction and analysis revealed 12 genes primarily linked to cervical insufficiency, the majority of which are known to cause collagenopathies. Ten patients carried disruptive variants potentially contributive to the development of non-syndromic cervical insufficiency. Pathway enrichment analysis of variant genes from our cohort revealed an increased variation burden in genes playing roles in tissue mechanical and biomechanical properties, i.e. collagen biosynthesis and cell-extracellular matrix communications. Consequently, the proposed idea of cervical insufficiency being a subtle form of collagenopathy, now strengthened by our genetic findings, might open up new opportunities for improved patient evaluation and management.

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Sentieon DNASeq Variant Calling Workflow Demonstrates Strong Computational Performance and Accuracy

Cited by 177 publications

References 17 publications

Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts

Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts

Haplotyping the Vitis collinear core genome with rhAmpSeq improves marker transferability in a diverse genus

Genetic landscape of preterm birth due to cervical insufficiency: Comprehensive gene analysis and patient next-generation sequencing data interpretation

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