Shortening the diagnostic odyssey—the impact of whole genome sequencing in the NHS

Abstract Saccharomyces cerevisiae is extensively utilized for commercial fermentation, and is also an important biological model; however, its ecology has only recently begun to be understood. Through the use of whole-genome sequencing, the species has been characterized into a number of distinct subpopulations, defined by geographical ranges and industrial uses. Here, the whole-genome sequences of 104 New Zealand (NZ) S. cerevisiae strains, including 52 novel genomes, are analyzed alongside 450 published sequences derived from various global locations. The impact of S. cerevisiae novel range expansion into NZ was investigated and these analyses reveal the positioning of NZ strains as a subgroup to the predominantly European/wine clade. A number of genomic differences with the European group correlate with range expansion into NZ, including 18 highly enriched single-nucleotide polymorphism (SNPs) and novel Ty1/2 insertions. While it is not possible to categorically determine if any genetic differences are due to stochastic process or the operations of natural selection, we suggest that the observation of NZ-specific copy number increases of four sugar transporter genes in the HXT family may reasonably represent an adaptation in the NZ S. cerevisiae subpopulation, and this correlates with the observations of copy number changes during adaptation in small-scale experimental evolution studies.

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Piglet Gut and in-Barn Manure from Farms on a Raised without Antibiotics Program Display Reduced Antimicrobial Resistance but an Increased Prevalence of Pathogens

Antibiotics ◽

10.3390/antibiotics10101152 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1152

Author(s):

Samuel M. Chekabab ◽

John R. Lawrence ◽

Alvin C. Alvarado ◽

Bernardo Z. Predicala ◽

Darren R. Korber

Keyword(s):

Antimicrobial Resistance ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Fecal Samples ◽

Time Points ◽

Conventional Farms ◽

Production Practices ◽

On Farm ◽

The Impact

In response to new stringent regulations in Canada regarding the use of antibiotics in animal production, many farms have implemented practices to produce animals that are raised without antibiotics (RWA) from birth to slaughter. This study aims to assess the impact of RWA production practices on reducing the actual total on-farm use of antibiotics, the occurrence of pathogens, and the prevalence of antimicrobial resistance (AMR). A 28-month longitudinal surveillance of farms that adopted the RWA program and conventional farms using antibiotics in accordance with the new regulations (non-RWA) was conducted by collecting fecal samples from 6-week-old pigs and composite manure from the barn over six time points and applying whole-genome sequencing (WGS) to assess the prevalence of AMR genes as well as the abundance of pathogens. Analysis of in-barn drug use records confirmed the decreased consumption of antibiotics in RWA barns compared to non-RWA barns. WGS analyses revealed that RWA barns had reduced the frequency of AMR genes in piglet feces and in-barn manure. However, metagenomic analyses showed that RWA barns had a significant increase in the frequency of pathogenic Firmicutes in fecal samples and pathogenic Proteobacteria in barn manure samples.

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Evaluation of whole genome sequencing for the identification and typing of Vibrio cholerae

10.1101/327973 ◽

2018 ◽

Author(s):

David R. Greig ◽

Ulf Schafer ◽

Sophie Octavia ◽

Ebony Hunter ◽

Marie A. Chattaway ◽

...

Keyword(s):

Public Health ◽

Whole Genome Sequencing ◽

Vibrio Cholerae ◽

Species Identification ◽

Genome Sequencing ◽

National Level ◽

Whole Genome ◽

Surveillance Programs ◽

El Tor ◽

The Impact

AbstractEpidemiological and microbiological data on Vibrio cholerae isolated between 2004 and 2017 (n=836) and held in the Public Health England culture archive were reviewed. The traditional biochemical species identification and serological typing results were compared with the genome derived species identification and serotype for a sub-set of isolates (n=152). Of the 836 isolates, 750 (89.7%) were from faecal specimens, 206 (24.6%) belonged to serogroup O1 and seven (0.8%) were serogroup O139, and 792 (94.7%) isolates from patients reporting recent travel abroad, most commonly to India (n=209) and Pakistan (n=104). Of the 152 isolates of V. cholerae speciated by kmer identification, 149 (98.1%) were concordant with the traditional biochemical approach. Traditional serotyping results were 100% concordant with the whole genome sequencing (WGS) analysis for identification of serogroups O1 and O139 and Classical and El Tor biotypes. ctxA was detected in all isolates of V. cholerae O1 El Tor and O139 belonging to sequence type (ST) 69, and in V. cholerae O1 Classical variants belonging to ST73. A phylogeny of isolates belonging to ST69 from UK travellers clustered geographically, with isolates from India and Pakistan located on separate branches. Moving forward, WGS data from UK travellers will contribute to global surveillance programs, and the monitoring of emerging threats to public health and the global dissemination of pathogenic lineages. At the national level, these WGS data will inform the timely reinforcement of direct public health messaging to travellers and mitigate the impact of imported infections and the associated risks to public health.

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Evaluation of Whole-Genome Sequencing for Identification and Typing of Vibrio cholerae

Journal of Clinical Microbiology ◽

10.1128/jcm.00831-18 ◽

2018 ◽

Vol 56 (11) ◽

Cited By ~ 12

Author(s):

David R. Greig ◽

Ulf Schaefer ◽

Sophie Octavia ◽

Ebony Hunter ◽

Marie A. Chattaway ◽

...

Keyword(s):

Public Health ◽

Whole Genome Sequencing ◽

Vibrio Cholerae ◽

Species Identification ◽

Genome Sequencing ◽

National Level ◽

Whole Genome ◽

Content Type ◽

El Tor ◽

The Impact

ABSTRACT Epidemiological and microbiological data on Vibrio cholerae strains isolated between April 2004 and March 2018 (n = 836) and held at the Public Health England culture archive were reviewed. The traditional biochemical species identification and serological typing results were compared with the genome-derived species identification and serotype for a subset of isolates (n = 152). Of the 836 isolates, 750 (89.7%) were from a fecal specimen, 206 (24.6%) belonged to serogroup O1, and 7 (0.8%) were serogroup O139; 792 (94.7%) isolates were from patients reporting recent travel abroad, most commonly to India (n = 209) and Pakistan (n = 104). Of the 152 V. cholerae isolates identified by use of kmer, 149 (98.1%) were concordant with those identified using the traditional biochemical approach. Traditional serotyping results were 100% concordant with those of the whole-genome sequencing (WGS) analysis for the identification of serogroups O1 and O139 and classical and El Tor biotypes. ctxA was detected in all isolates of V. cholerae O1 El Tor and O139 belonging to sequence type 69 (ST69) and in V. cholerae O1 classical variants belonging to ST73. A phylogeny of isolates belonging to ST69 from U.K. travelers clustered geographically, with isolates from India and Pakistan located on separate branches. Moving forward, WGS data from U.K. travelers will contribute to global surveillance programs and the monitoring of emerging threats to public health and the global dissemination of pathogenic lineages. At the national level, these WGS data will inform the timely reinforcement of direct public health messaging to travelers and mitigate the impact of imported infections and the associated risks to public health.

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Whole Genome Sequencing of A(H3N2) Influenza Viruses Reveals Variants Associated with Severity during the 2016–2017 Season

Viruses ◽

10.3390/v11020108 ◽

2019 ◽

Vol 11 (2) ◽

pp. 108 ◽

Cited By ~ 10

Author(s):

Bruno Simon ◽

Maxime Pichon ◽

Martine Valette ◽

Gwendolyne Burfin ◽

Mathilde Richard ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Influenza Viruses ◽

Influenza Surveillance ◽

Whole Genome ◽

University Hospitals ◽

Surveillance Network ◽

Genetic Traits ◽

H3n2 Influenza ◽

The Impact

Influenza viruses cause a remarkable disease burden and significant morbidity and mortality worldwide, and these impacts vary between seasons. To understand the mechanisms associated with these differences, a comprehensive approach is needed to characterize the impact of influenza genomic traits on the burden of disease. During 2016–2017, a year with severe A(H3N2), we sequenced 176 A(H3N2) influenza genomes using next generation sequencing (NGS) for routine surveillance of circulating influenza viruses collected via the French national influenza community-based surveillance network or from patients hospitalized in the intensive care units of the University Hospitals of Lyon, France. Taking into account confounding factors, sequencing and clinical data were used to identify genomic variants and quasispecies associated with influenza severity or vaccine failure. Several amino acid substitutions significantly associated with clinical traits were found, including NA V263I and NS1 K196E which were associated with severity and co-occurred only in viruses from the 3c.2a1 clade. Additionally, we observed that intra-host diversity as a whole and on a specific set of gene segments increased with severity. These results support the use of whole genome sequencing as a tool for the identification of genetic traits associated with severe influenza in the context of influenza surveillance.

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Noninvasive prenatal screening for patients with high body mass index: Evaluating the impact of a customized whole genome sequencing workflow on sensitivity and residual risk

Prenatal Diagnosis ◽

10.1002/pd.5603 ◽

2019 ◽

Vol 40 (3) ◽

pp. 333-341

Author(s):

Dale Muzzey ◽

James D. Goldberg ◽

Carrie Haverty

Keyword(s):

Body Mass Index ◽

Whole Genome Sequencing ◽

Body Mass ◽

Genome Sequencing ◽

Prenatal Screening ◽

High Body Mass Index ◽

Residual Risk ◽

Whole Genome ◽

High Body ◽

The Impact

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Assessing reproducibility of inherited variants detected with short-read whole genome sequencing

Genome Biology ◽

10.1186/s13059-021-02569-8 ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Bohu Pan ◽

Luyao Ren ◽

Vitor Onuchic ◽

Meijian Guan ◽

Rebecca Kusko ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Precision Medicine ◽

Genome Sequencing ◽

Whole Genome ◽

Single Nucleotide Variants ◽

Short Read ◽

Sequencing Platforms ◽

The Impact ◽

Two Populations

Abstract Background Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. Conclusions Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.

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SeroBA: rapid high-throughput serotyping of Streptococcus pneumoniae from whole genome sequence data

10.1101/179465 ◽

2017 ◽

Author(s):

Lennard Epping ◽

Andries J. van Tonder ◽

Rebecca A. Gladstone ◽

Stephen D. Bentley ◽

Andrew J. Page ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome Sequence ◽

Validation Dataset ◽

List Type ◽

Whole Genome ◽

Link Type ◽

Computational Performance ◽

The Impact

ABSTRACTStreptococcus pneumoniae is responsible for 240,000 - 460,000 deaths in children under 5 years of age each year. Accurate identification of pneumococcal serotypes is important for tracking the distribution and evolution of serotypes following the introduction of effective vaccines. Recent efforts have been made to infer serotypes directly from genomic data but current software approaches are limited and do not scale well. Here, we introduce a novel method, SeroBA, which uses a hybrid assembly and mapping approach. We compared SeroBA against real and simulated data and present results on the concordance and computational performance against a validation dataset, the robustness and scalability when analysing a large dataset, and the impact of varying the depth of coverage in the cps locus region on sequence-based serotyping. SeroBA can predict serotypes, by identifying the cps locus, directly from raw whole genome sequencing read data with 98% concordance using a k-mer based method, can process 10,000 samples in just over 1 day using a standard server and can call serotypes at a coverage as low as 10x. SeroBA is implemented in Python3 and is freely available under an open source GPLv3 license from: https://github.com/sanger-pathogens/seroba.DATA SUMMARYThe reference genome Streptococcus pneumoniae ATCC 700669 is available from National Center for Biotechnology Information (NCBI) with the accession number: FM211187Simulated paired end reads for experiment 2 have been deposited in FigShare: https://doi.org/10.6084/m9.figshare.5086054.v1Accession numbers for all other experiments are listed in Supplementary Table S1 and Supplementary Table S2.I/We confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. ⊠IMPACT STATEMENTThis article describes SeroBA, a A-mer based method for predicting the serotypes of Streptococcus pneumoniae from Whole Genome Sequencing (WGS) data. SeroBA can identify 92 serotypes and 2 subtypes with constant memory usage and low computational costs. We showed that SeroBA is able to reliably predict serotypes at a depth of coverage as low as 10x and is scalable to large datasets.

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OP01.02: NIPS for high-BMI patients: evaluating the impact of deep whole-genome sequencing on sensitivity and residual risk

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.19392 ◽

2018 ◽

Vol 52 ◽

pp. 66-66

Author(s):

C.E. Haverty ◽

K.M. D'Auria ◽

K.R. Haas ◽

H.P. Kang ◽

E.A. Evans ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Residual Risk ◽

Whole Genome ◽

The Impact ◽

High Bmi

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Viral whole-genome sequencing to assess impact of universal masking on SARS-CoV-2 transmission among pediatric healthcare workers

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2021.415 ◽

2021 ◽

pp. 1-5

Author(s):

Larry K. Kociolek ◽

Ami B. Patel ◽

Judd F. Hultquist ◽

Egon A. Ozer ◽

Lacy M. Simons ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Healthcare Workers ◽

Phylogenetic Analyses ◽

Whole Genome ◽

Free Standing ◽

Children's Hospital ◽

Children’S Hospital ◽

Quasi Experimental ◽

The Impact

Abstract Objective: To identify the impact of universal masking on COVID-19 incidence and putative SARS-CoV-2 transmissions events among children’s hospital healthcare workers (HCWs). Design: Quasi-experimental study. Setting: Single academic free-standing children’s hospital. Methods: We performed whole-genome sequencing of SARS-CoV-2- PCR-positive samples collected from HCWs 3 weeks before and 6 weeks after implementing a universal masking policy. Phylogenetic analyses were performed to identify clusters of clonally related SARS-CoV-2 indicative of putative transmission events. We measured COVID-19 incidence, SARS-CoV-2 test positivity rates, and frequency of putative transmission events before and after the masking policy was implemented. Results: HCW COVID-19 incidence and test positivity declined from 14.3 to 4.3 cases per week, and from 18.4% to 9.0%, respectively. Putative transmission events were only identified prior to universal masking. Conclusions: A universal masking policy was associated with reductions in HCW COVID-19 infections and occupational acquisition of SARS-CoV-2.

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