Comparison of somatic mutation calling methods in amplicon and whole exome sequence data

Xu, Huilei; DiCarlo, John; Satya, Ravi Vijaya; Quan, Peng; Wang, Yexun

doi:10.1186/1471-2164-15-244

Cited by 140 publications

(148 citation statements)

References 26 publications

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“…Variant calling was executed with GATK software and low quality variants (mapping quality below 30, read depth below 10 or frequency < 10%), were discarded (18). GATK has been proved to achieve higher sensitivity and specificity in exome variant calling than other softwares (19). Germline variants were also removed, i.e., variants that were present in normal adjacent paired sequence for each tumor, and variants reported in the 1000G project.…”

Section: Methodsmentioning

confidence: 99%

Exome Sequencing Reveals AMER1 as a Frequently Mutated Gene in Colorectal Cancer

Sanz‐Pamplona

López-Dóriga

Paré

et al. 2015

Clinical Cancer Research

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PURPOSE Somatic mutations occur at early stages of adenoma and accumulate throughout colorectal cancer (CRC) progression. The aim of this study was to characterize the mutational landscape of stage II tumors and to search for novel recurrent mutations likely implicated in CRC tumorigenesis. DESIGN The exomic DNA of 42 stage II, microsatellite stable, colon tumors and their paired mucosae were sequenced. Other molecular data available in the discovery dataset (gene expression, methylation, and CNV) was used to further characterize these tumors. Additional datasets comprising 553 CRC samples were used to validate the discovered mutations. RESULTS As a result, 4,886 somatic single nucleotide variants (SNVs) were found. Almost all SNVs were private changes, with few mutations shared by more than one tumor, thus revealing tumor-specific mutational landscapes. Nevertheless, these diverse mutations converged into common cellular pathways such as cell cycle or apoptosis. Among this mutational heterogeneity, variants resulting in early stop-codons in the AMER1 (also known as FAM123B or WTX) gene emerged as recurrent mutations in CRC. Loses of AMER1 by other mechanisms apart from mutations such as methylation and copy number aberrations were also found. Tumors lacking this tumor suppressor gene exhibited a mesenchymal phenotype characterized by inhibition of the canonical Wnt pathway. CONCLUSION In silico and experimental validation in independent datasets confirmed the existence of functional mutations in AMER1 in approximately 10% of analyzed CRC tumors. Moreover, these tumors exhibited a characteristic phenotype.

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Section: Methodsmentioning

confidence: 99%

Exome Sequencing Reveals AMER1 as a Frequently Mutated Gene in Colorectal Cancer

Sanz‐Pamplona

López-Dóriga

Paré

et al. 2015

Clinical Cancer Research

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“…This is highly indicative that sequencing protocols and computational methods, including the read aligners, have a major impact on the sensitivity and specificity of SNV calling [27]. Specifically, the fraction of the variant allele as well as the coverage, i. e. the number of reads that are aligned to a site with a potential SNV are crucial determinants for the statistical benchmarks [35]. Additional rigorous postprocessing steps are suggested to improve the SNV calling.…”

Section: Genome Resequencing and Variation Callingmentioning

confidence: 98%

Read mapping

Hoffmann

Stadler

2016

It - Information Technology

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The Read Mapping problem asks for the exact origin of a nucleotide sequence in a reference genome. It translates to a conceptually simple approximate string matching problem. The practical difficulty, however, arises from the typical size of the data sets produced by modern high throughput sequencing technologies, from the biological processes involved in derivation of the query molecule from its genomic source, and from the technical processes of the sequencing technology itself.

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“…VarScan 2 applies Fisher's exact test to the tumor and normal allele frequencies obtained from a pileup file (18). Strelka identifies low-allelic-fraction candidate mutations with high sensitivity, whereas VarScan 2 detects little low-allelic-fraction candidates (6,29). Therefore, tumor purity has a relatively higher impact on the numbers of variants detected by VarScan 2.…”

Section: Discussionmentioning

confidence: 99%

Construction of a combinatorial pipeline using two somatic variant calling methods for whole exome sequence data of gastric cancer

et al. 2017

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: High -throughput next-generation sequencing is a powerful tool to identify the genotypic landscapes of somatic variants and therapeutic targets in various cancers including gastric cancer, forming the basis for personalized medicine in the clinical setting. Although the advent of many computational algorithms leads to higher accuracy in somatic variant calling, no standard method exists due to the limitations of each method. Here, we constructed a new pipeline. We combined two different somatic variant callers with different algorithms, Strelka and VarScan 2, and evaluated performance using whole exome sequencing data obtained from 19 Japanese cases with gastric cancer (GC) ; then, we characterized these tumors based on identified driver molecular alterations. More single nucleotide variants (SNVs) and small insertions/deletions were detected by Strelka and VarScan 2, respectively. SNVs detected by both tools showed higher accuracy for estimating somatic variants compared with those detected by only one of the two tools and accurately showed the mutation signature and mutations of driver genes reported for GC. Our combinatorial pipeline may have an advantage in detection of somatic mutations in GC and may be useful for further genomic characterization of Japanese patients with GC to improve the efficacy of GC treatments.

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Comparison of somatic mutation calling methods in amplicon and whole exome sequence data

Cited by 140 publications

References 26 publications

Exome Sequencing Reveals AMER1 as a Frequently Mutated Gene in Colorectal Cancer

Exome Sequencing Reveals AMER1 as a Frequently Mutated Gene in Colorectal Cancer

Read mapping

Construction of a combinatorial pipeline using two somatic variant calling methods for whole exome sequence data of gastric cancer

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