Comparing Variant Call Files for Performance Benchmarking of Next-Generation Sequencing Variant Calling Pipelines

Cleary, John G.; Braithwaite, Ross; Gaastra, Kurt; Hilbush, Brian S.; Inglis, Stuart J.; Irvine, Sean A.; Jackson, Alan A.; Littin, Richard; Rathod, Mehul; Ware, David; Zook, Justin M.; Trigg, Len; Vega, Francisco M. M. De La

doi:10.1101/023754

Cited by 205 publications

(196 citation statements)

References 9 publications

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“…Additionally, alignment and SNP calling to the BO5.10 mitochondrial and later the genomic reference sequence, that was published during our analyses (JA Kan Van et al 2017), was also conducted using the same methodologies. However, while individual SNP and indel statistics were determined from separate isolate specific vcfs using SnpEff (Cingolani et al 2012) for the pilot study, the statistics for these larger datasets were determined using VcfStats v1.2 (Lindenbaum 2015) and rtg-tools-3.8.3 (Cleary et al 2015) as a group. While SNPeff and VcfStats/rtgtools give the same total number of indels and SNPs for the isolates as a whole, individual indel numbers deviated from the pilot study.…”

Section: Polymorphism Detectionmentioning

confidence: 99%

Resequencing and association mapping of the generalist pathogenBotrytis cinerea

Atwell

Corwin

Soltis

et al. 2018

Preprint

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We performed whole genome resequencing of 84 field isolates of Botrytis cinerea, largely collected from a local set of plant species. Combined with 13 previously resequenced isolates sampled from diverse locations, this gave a collection of 97 isolates for studies of natural variation. Alignment to the reference sequence T4 and SNP detection provided further data for population genetics analysis including a mapping population for association studies. Although much of the genomic diversity was captured in the original 13 isolates, the additional genomes increased total diversity in the population by a third. Surprisingly, the same additional genomes increase mitochondrial diversity 2-fold. Across the population, LD was limited and decayed rapidly, reflecting frequent outcrossings. Effectively, this sampling strategy increased the level of genetic diversity available, whilst limiting the problem of population stratification and enabling GWAS of several phenotypes on common Arabidopsis plants affected in disease pathways.Overlap of results using all GWAS methods revealed numerous candidate genes / pathways that potentially contribute to its broad host range and offer conceivable pathogen decrease targets.

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Section: Polymorphism Detectionmentioning

confidence: 99%

Resequencing and association mapping of the generalist pathogenBotrytis cinerea

Atwell

Corwin

Soltis

et al. 2018

Preprint

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“…The performance of algorithms was evaluated by means of the PT reference in software rtgtools[15] and vcfeval [16].…”

Section: Statistical Evaluation By Means Of the Pt Reference Mutationmentioning

confidence: 99%

FPfilter: A false-positive-specific filter for whole-genome sequencing variant calling from GATK

Tan

Zhang

Yang

et al. 2020

Preprint

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Tel/ Fax: +86-020-85222787 1. Abstract:Motivation: As whole genome sequencing (WGS) is becoming cost-effective progressivelly, it has been applied increasingly in medical and scientific fields.Although the traditional variant-calling pipeline (BWA+GATK) has very high accuracy, false positives (FPs) are still an unavoidable problem that might lead to unfavorable outcomes, especially in clinical applications. As a result, filtering out FPs is recommended after variant calling. However, loss of true positives (TPs) is inevitable in FP-filtering methods, such as GATK hard filtering (GATK-HF).Therefore, to minimize the loss of TPs and maximize the filtration of FPs, a comprehensive understanding of the features of TPs and FPs, and building an improved model of classification are necessary. To obtain information about TPs and FPs, we used Platinum Genome (PT) as the mutation reference and its 300× deep sequenced dataset NA12878 as the simulation template. Then random sampling across depth gradients from NA12878 was performed to study the depth effect.Results: FPs among heterozygous mutations were found to have pattern distinct from that of FPs among homozygous mutations. FPfilter makes use of this model to filter out FPs specifically. We evaluated FPfilter on a training dataset with depth gradients from NA12878 and a test dataset from NA12877 and NA24385. Compared with GATK-HF, FPfilter showed a significantly higher FP/TP filtration ratio and F-measure score. Our results indicate that FPfilter provides an improved model for distinguishing FPs from TPs and filters FPs with high specificity.Availability: FPfilter is freely available for download on GitHub (https://github.com/yuxiangtan/FPfilter). Users can easily install it from anaconda.

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“…We implemented the simulation based on the Real Time Genomics (RTG) simulation tool [32]. RTG provides a blueprint platform for genomic analysis.…”

Section: Simulationmentioning

confidence: 99%

VSIM: Visualization and simulation of variants in personal genomes with an application to premarital testing

Althagafi

Hoehndorf

2019

Preprint

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Background: Interpretation of personal genomics data, for example in genetic counseling, is challenging due to the complexity of the data and the amount of background knowledge required for its interpretation. This background knowledge is distributed across several databases. Further information about genomic features can also be predicted through machine learning methods. Making this information accessible more easily has the potential to improve interpretation of variants in personal genomes.Results: We have developed VSIM, a web application for the interpretation and visualization of variants in personal genome sequences. VSIM identifies disease variants related to Mendelian, complex, and digenic disease as well as pharmacogenomic variants in personal genomes and visualizes them using a webserver. VSIM can further be used to simulate populations of children based on two parent genomes, and can be applied to support premarital genetic counseling. We make VSIM available as source code as well as through a container that can be installed easily in network environments in which genomic data is specially protected. VSIM and related documentation is freely available at https://github.com/bio-ontology-research-group/VSIM.Conclusions: VSIM is a software that provides a web-based interface to variant interpretation in genetic counseling. VSIM can also be used for premarital genetic screening by simulating a population of children and analyze the disorder they might be carrying.

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Comparing Variant Call Files for Performance Benchmarking of Next-Generation Sequencing Variant Calling Pipelines

Cited by 205 publications

References 9 publications

Resequencing and association mapping of the generalist pathogenBotrytis cinerea

Resequencing and association mapping of the generalist pathogenBotrytis cinerea

FPfilter: A false-positive-specific filter for whole-genome sequencing variant calling from GATK

VSIM: Visualization and simulation of variants in personal genomes with an application to premarital testing

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