SomaticSniper: identification of somatic point mutations in whole genome sequencing data

Low-coverage or shallow whole genome sequencing (sWGS) approaches can efficiently detect somatic copy number aberrations (SCNAs) at low cost. This is clinically important for many cancers, in particular cancers with severe chromosomal instability (CIN) that frequently lack actionable point mutations and are characterised by poor disease outcome. Absolute copy number (ACN), measured in DNA copies per cancer cell, is required for meaningful comparisons between copy number states, but is challenging to estimate and in practice often requires manual curation. Using a total of 60 cancer cell lines, 148 patient-derived xenograft (PDX) and 142 clinical tissue samples, we evaluate the performance of available tools for obtaining ACN from sWGS. We provide a validated and refined tool called Rascal (relative to absolute copy number scaling) that provides improved fitting algorithms and enables interactive visualisation of copy number profiles. These approaches are highly applicable to both pre-clinical and translational research studies on SCNA-driven cancers and provide more robust ACN fits from sWGS data than currently available tools.

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Prediction of antimicrobial resistance in clinical Campylobacter jejuni isolates from whole-genome sequencing data

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-020-04043-y ◽

2020 ◽

Author(s):

Louise Gade Dahl ◽

Katrine Grimstrup Joensen ◽

Mark Thomas Østerlund ◽

Kristoffer Kiil ◽

Eva Møller Nielsen

Keyword(s):

Antimicrobial Resistance ◽

Whole Genome Sequencing ◽

Campylobacter Jejuni ◽

Genome Sequencing ◽

Resistance Genes ◽

Point Mutations ◽

23S Rrna ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data

Abstract Campylobacter jejuni is recognised as the leading cause of bacterial gastroenteritis in industrialised countries. Although the majority of Campylobacter infections are self-limiting, antimicrobial treatment is necessary in severe cases. Therefore, the development of antimicrobial resistance (AMR) in Campylobacter is a growing public health challenge and surveillance of AMR is important for bacterial disease control. The aim of this study was to predict antimicrobial resistance in C. jejuni from whole-genome sequencing data. A total of 516 clinical C. jejuni isolates collected between 2014 and 2017 were subjected to WGS. Resistance phenotypes were determined by standard broth dilution, categorising isolates as either susceptible or resistant based on epidemiological cutoffs for six antimicrobials: ciprofloxacin, nalidixic acid, erythromycin, gentamicin, streptomycin, and tetracycline. Resistance genotypes were identified using an in-house database containing reference genes with known point mutations and the presence of resistance genes was determined using the ResFinder database and four bioinformatical methods (modified KMA, ABRicate, ARIBA, and ResFinder Batch Upload). We identified seven resistance genes including tet(O), tet(O/32/O), ant(6)-Ia, aph(2″)-If, blaOXA, aph(3′)-III, and cat as well as mutations in three genes: gyrA, 23S rRNA, and rpsL. There was a high correlation between phenotypic resistance and the presence of known resistance genes and/or point mutations. A correlation above 98% was seen for all antimicrobials except streptomycin with a correlation of 92%. In conclusion, we found that WGS can predict antimicrobial resistance with a high degree of accuracy and have the potential to be a powerful tool for AMR surveillance.

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From whole genome sequencing data toward a simple genotyping tool: application to the animal pathogen Mycobacterium bovis

10.26226/morressier.56d5ba2ad462b80296c965c0 ◽

2016 ◽

Author(s):

Lorraine Michelet

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Mycobacterium Bovis ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data

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Plasmids or no plasmids? A comparison between the agilent TapeStation and whole-genome sequencing data in a large-scale bacterial sequencing project

10.26226/morressier.56d5ba27d462b80296c95fe7 ◽

2016 ◽

Author(s):

Sarah Alexander

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Large Scale ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data ◽

Sequencing Project

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Risk prediction and marker selection in nonsynonymous single nucleotide polymorphisms using whole genome sequencing data

Animal Cells and Systems ◽

10.1080/19768354.2020.1860125 ◽

2020 ◽

Vol 24 (6) ◽

pp. 321-328

Author(s):

Young-Sup Lee ◽

KyeongHye Won ◽

Donghyun Shin ◽

Jae-Don Oh

Keyword(s):

Single Nucleotide Polymorphisms ◽

Whole Genome Sequencing ◽

Risk Prediction ◽

Genome Sequencing ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Nucleotide Polymorphisms ◽

Sequencing Data ◽

Single Nucleotide ◽

Marker Selection

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Development and evaluation of an outbreak surveillance system integrating whole genome sequencing data for non-typhoidal Salmonella in London and South East of England, 2016-17

Epidemiology and Infection ◽

10.1017/s0950268821001400 ◽

2021 ◽

pp. 1-26

Author(s):

Karthik Paranthaman ◽

Piers Mook ◽

Daniele Curtis ◽

Edward-Wynne Evans ◽

Emma Crawley-Boevey ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Surveillance System ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data

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Whole genome sequencing reveals high differentiation, low levels of genetic diversity and short runs of homozygosity among Swedish wels catfish

Heredity ◽

10.1038/s41437-021-00438-5 ◽

2021 ◽

Author(s):

Axel Jensen ◽

Mette Lillie ◽

Kristofer Bergström ◽

Per Larsson ◽

Jacob Höglund

Keyword(s):

Genetic Diversity ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome Sequencing Data ◽

Peripheral Populations ◽

Whole Genome ◽

Runs Of Homozygosity ◽

Sequencing Data ◽

Isolated Populations ◽

Native Populations

AbstractThe use of genetic markers in the context of conservation is largely being outcompeted by whole-genome data. Comparative studies between the two are sparse, and the knowledge about potential effects of this methodology shift is limited. Here, we used whole-genome sequencing data to assess the genetic status of peripheral populations of the wels catfish (Silurus glanis), and discuss the results in light of a recent microsatellite study of the same populations. The Swedish populations of the wels catfish have suffered from severe declines during the last centuries and persists in only a few isolated water systems. Fragmented populations generally are at greater risk of extinction, for example due to loss of genetic diversity, and may thus require conservation actions. We sequenced individuals from the three remaining native populations (Båven, Emån, and Möckeln) and one reintroduced population of admixed origin (Helge å), and found that genetic diversity was highest in Emån but low overall, with strong differentiation among the populations. No signature of recent inbreeding was found, but a considerable number of short runs of homozygosity were present in all populations, likely linked to historically small population sizes and bottleneck events. Genetic substructure within any of the native populations was at best weak. Individuals from the admixed population Helge å shared most genetic ancestry with the Båven population (72%). Our results are largely in agreement with the microsatellite study, and stresses the need to protect these isolated populations at the northern edge of the distribution of the species.

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