Data Processing and Germline Variant Calling with the Sentieon Pipeline

Aldana, Rafael; Freed, Donald

doi:10.1007/978-1-0716-2293-3_1

Cited by 11 publications

(8 citation statements)

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“…Library construction and WGS were conducted at BGI Genomics (BGI-Shenzhen) as previously described 18 . The WGS data were then processed under the Genome Analysis Toolkit (GATK) best practice guidance using Sentieon (release 201808.05) 70 . All of the reads were mapped to the non-N reference sequence of genome build GRCh38.…”

Section: Methodsmentioning

confidence: 99%

The STROMICS genome study: deep whole-genome sequencing and analysis of 10K Chinese patients with ischemic stroke reveal complex genetic and phenotypic interplay

Cheng

Bian

et al. 2023

Cell Discov

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Ischemic stroke is a leading cause of global mortality and long-term disability. However, there is a paucity of whole-genome sequencing studies on ischemic stroke, resulting in limited knowledge of the interplay between genomic and phenotypic variations among affected patients. Here, we outline the STROMICS design and present the first whole-genome analysis on ischemic stroke by deeply sequencing and analyzing 10,241 stroke patients from China. We identified 135.59 million variants, > 42% of which were novel. Notable disparities in allele frequency were observed between Chinese and other populations for 89 variants associated with stroke risk and 10 variants linked to response to stroke medications. We investigated the population structure of the participants, generating a map of genetic selection consisting of 31 adaptive signals. The adaption of the MTHFR rs1801133-G allele, which links to genetically evaluated VB9 (folate acid) in southern Chinese patients, suggests a gene-specific folate supplement strategy. Through genome-wide association analysis of 18 stroke-related traits, we discovered 10 novel genetic-phenotypic associations and extensive cross-trait pleiotropy at 6 lipid-trait loci of therapeutic relevance. Additionally, we found that the set of loss-of-function and cysteine-altering variants present in the causal gene NOTCH3 for the autosomal dominant stroke disorder CADASIL displayed a broad neuro-imaging spectrum. These findings deepen our understanding of the relationship between the population and individual genetic layout and clinical phenotype among stroke patients, and provide a foundation for future efforts to utilize human genetic knowledge to investigate mechanisms underlying ischemic stroke outcomes, discover novel therapeutic targets, and advance precision medicine.

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Section: Methodsmentioning

confidence: 99%

The STROMICS genome study: deep whole-genome sequencing and analysis of 10K Chinese patients with ischemic stroke reveal complex genetic and phenotypic interplay

Cheng

Bian

et al. 2023

Cell Discov

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“…Library construction and WGS were conducted at BGI Genomics (BGI‐Shenzhen), as previously described 24 . The WGS data were then processed under the Genome Analysis Toolkit best practice guidance using Sentieon (release 201808.05) 25 . The data of the 11 SNPs were extracted from the CNSR‐III WGS data.…”

Section: Methodsmentioning

confidence: 99%

“…24 The WGS data were then processed under the Genome Analysis Toolkit best practice guidance using Sentieon (release 201808.05). 25 The data of the 11 SNPs were extracted from the CNSR-III WGS data.…”

Section: Detection Of Single Nucleotide Polymorphismsmentioning

confidence: 99%

Variants within the LPL gene confer susceptility to diabetic kidney disease and rapid decline in kidney function in Chinese patients with type 2 diabetes

Cheng

et al. 2023

Diabetes Obesity Metabolism

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AimTo examine the association between lipoprotein lipase (LPL) polymorphisms and susceptibility to diabetic kidney disease (DKD) and early renal function decline in Chinese patients with type 2 diabetes (T2D).MethodsThe association of eight LPL single nucleotide polymorphisms (SNPs) with DKD was analysed in 2793 patients with T2D from the third China National Stroke Registry. DKD was defined as either an urine albumin‐to‐creatinine ratio (UACR) of 30 mg/g or higher at baseline and 3 months, or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 at baseline and 3 months. Rapid decline in kidney function (RDKF) was defined as a reduction in the eGFR of 3 mL/min/1.73 m2 or greater per year. Logistic regression models were used to evaluate the association of LPL SNP and DKD with an additive model.ResultsThe SNPs rs285 C>T (OR = 1.40, P = .0154), rs328 C>G (OR = 2.24, P = .0104) and rs3208305 A>T (OR = 1.85, P = .0015) were identified to be significantly associated with DKD defined by eGFR. Among 1241 participants with follow‐up data, 441 (35.5%) showed RDKF over a mean follow‐up period of 1 year, and the rs285 C allele was associated with higher odds of RDKF (OR = 1.31, 95% CI 1.04‐1.66; P = .025) after adjustment for multiple variables.ConclusionsThese results suggest that LPL‐related SNPs are new candidate factors for conferring susceptibility to DKD and may promote rapid loss of renal function in Chinese patients with T2D.

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“…This was followed by sequencing using a paired-end 2 x 150 bp protocol on an Illumina HiSeq instrument. A custom optimized version of Sentieon 68 was applied to preprocess sequencings reads, align reads to human genome using GRCh37 (hg19) assembly as reference, and conduct single nucleotide variant (SNV) calling using algorithms following the GATK best-practice pipeline 69,70 . After GATK’s VQSR quality control, hard filtering was applied to remove the variants with 1) Read depth (DP) <10; 2) Allelic Balance (AB) > 0.8 or < 0.2 for heterozygous genotype; 3) Genotype quality (GQ) < 30.…”

Section: Methodsmentioning

confidence: 99%

Large-Scale Whole-Exome Sequencing Association Study Implicates Genetic Effects on Viral Oncogenesis and Tumor Microenvironment in Nasopharyngeal Carcinoma

Zeng,

Luo,

Lin

et al. 2023

Preprint

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Nasopharyngeal carcinoma (NPC) presents a substantial clinical challenge with limited understanding of its genetic underpinnings. Here we conduct the largest-scale whole-exome sequencing association study of NPC to date, involving 6,969 NPC cases and 7,100 controls and revealing three novel germline genetic variants linked to NPC susceptibility: a common variant in RPL14, a rare variant in SELE, and a common variant in HLA-B. Through multiomics analyses that incorporate both bulk (n=206) and single-cell RNA-sequencing (n=56) data, coupled with experimental validations, we demonstrate that RPL14, with pronounced significance in familial NPC cases, is linked with Epstein-Barr virus (EBV) life cycle and NPC pathogenesis. Furthermore, our study uncovers SELE as an NPC-associated gene with mutations potentially reshaping the tumor microenvironment (TME) dynamics. Leveraging whole-exome sequencing data, we highlight the critical impact of rare variants on NPC heritability and introduce a refined composite polygenic risk score (rcPRS) that outperforms existing models in predicting NPC risk. Collectively, our findings elucidate the multifaceted genetic architecture of NPC, providing valuable insights into the pathogenic mechanism how genetic susceptibility coping with EBV and TME predispose to NPC and potentials to steer personalized risk assessments, early diagnosis strategies, and therapeutic avenues.

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Data Processing and Germline Variant Calling with the Sentieon Pipeline

Cited by 11 publications

References 1 publication

The STROMICS genome study: deep whole-genome sequencing and analysis of 10K Chinese patients with ischemic stroke reveal complex genetic and phenotypic interplay

The STROMICS genome study: deep whole-genome sequencing and analysis of 10K Chinese patients with ischemic stroke reveal complex genetic and phenotypic interplay

Variants within the LPL gene confer susceptility to diabetic kidney disease and rapid decline in kidney function in Chinese patients with type 2 diabetes

Large-Scale Whole-Exome Sequencing Association Study Implicates Genetic Effects on Viral Oncogenesis and Tumor Microenvironment in Nasopharyngeal Carcinoma

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