scholarly journals Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index: a Rapid and Accessible Tool That Exploits Genomic Data in Public Health and Clinical Microbiology Applications

2020 ◽  
Vol 59 (1) ◽  
pp. e02161-20
Author(s):  
Charlene M. C. Rodrigues ◽  
Keith A. Jolley ◽  
Andrew Smith ◽  
J. Claire Cameron ◽  
Ian M. Feavers ◽  
...  

ABSTRACTAs microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole-genome sequence data by nonspecialists becomes essential. In the absence of capsule-based vaccines, two protein-based vaccines have been used for the prevention of invasive serogroup B meningococcal disease (IMD) since their licensure in 2013 and 2014. These vaccines have different components and different levels of coverage of meningococcal variants. Hence, decisions regarding which vaccine to use in managing serogroup B IMD outbreaks require information about the index case isolate, including (i) the presence of particular vaccine antigen variants, (ii) the expression of vaccine antigens, and (iii) the likely susceptibility of its antigen variants to antibody-dependent bactericidal killing. To obtain this information requires a multitude of laboratory assays, impractical in real-time clinical settings, where the information is most urgently needed. To facilitate assessment for public health and clinical purposes, we synthesized genomic and experimental data from published sources to develop and implement the Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index, which is publicly available on PubMLST (https://pubmlst.org). Using whole-genome sequences or individual gene sequences obtained from IMD isolates or clinical specimens, the MenDeVAR Index provides rapid evidence-based information on the presence and possible immunological cross-reactivity of different meningococcal vaccine antigen variants. The MenDeVAR Index enables practitioners who are not genomics specialists to assess the likely reactivity of vaccines for individual cases, outbreak management, or the assessment of public health vaccine programs. The MenDeVAR Index has been developed in consultation with, but independently of, both the 4CMenB (Bexsero; GSK) and rLP2086 (Trumenba; Pfizer, Inc.) vaccine manufacturers.

2020 ◽  
Author(s):  
Charlene M.C. Rodrigues ◽  
Keith A. Jolley ◽  
Andrew Smith ◽  
J. Claire Cameron ◽  
Ian M. Feavers ◽  
...  

AbstractAs microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole genome sequence data by non-specialists becomes essential. In the absence of capsule-based vaccines, two protein-based vaccines have been used for the prevention of invasive serogroup B meningococcal disease (IMD), since their licensure in 2013/14. These vaccines have different components and different coverage of meningococcal variants. Hence, decisions regarding which vaccine to use in managing serogroup B IMD outbreaks require information about the index case isolate including: (i) the presence of particular vaccine antigen variants; (ii) the expression of vaccine antigens; and (iii) the likely susceptibility of its antigen variants to antibody-dependent bactericidal killing. To obtain this information requires a multitude of laboratory assays, impractical in real-time clinical settings, where the information is most urgently needed. To facilitate assessment for public health and clinical purposes, we synthesised genomic and experimental data from published sources to develop and implement the ‘Meningococcal Deduced Vaccine Antigen Reactivity’ (MenDeVAR) Index, which is publicly-available on PubMLST (https://pubmlst.org). Using whole genome sequences or individual gene sequences obtained from IMD isolates or clinical specimens, MenDeVAR provides rapid evidence-based information on the presence and possible immunological cross-reactivity of different meningococcal vaccine antigen variants. The MenDeVAR Index enables practitioners who are not genomics specialists to assess the likely reactivity of vaccines for individual cases, outbreak management, or the assessment of public health vaccine programmes. MenDeVAR has been developed in consultation with, but independently of, both vaccine manufacturers.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jayanthi Gangiredla ◽  
Hugh Rand ◽  
Daniel Benisatto ◽  
Justin Payne ◽  
Charles Strittmatter ◽  
...  

Abstract Background Processing and analyzing whole genome sequencing (WGS) is computationally intense: a single Illumina MiSeq WGS run produces ~ 1 million 250-base-pair reads for each of 24 samples. This poses significant obstacles for smaller laboratories, or laboratories not affiliated with larger projects, which may not have dedicated bioinformatics staff or computing power to effectively use genomic data to protect public health. Building on the success of the cloud-based Galaxy bioinformatics platform (http://galaxyproject.org), already known for its user-friendliness and powerful WGS analytical tools, the Center for Food Safety and Applied Nutrition (CFSAN) at the U.S. Food and Drug Administration (FDA) created a customized ‘instance’ of the Galaxy environment, called GalaxyTrakr (https://www.galaxytrakr.org), for use by laboratory scientists performing food-safety regulatory research. The goal was to enable laboratories outside of the FDA internal network to (1) perform quality assessments of sequence data, (2) identify links between clinical isolates and positive food/environmental samples, including those at the National Center for Biotechnology Information sequence read archive (https://www.ncbi.nlm.nih.gov/sra/), and (3) explore new methodologies such as metagenomics. GalaxyTrakr hosts a variety of free and adaptable tools and provides the data storage and computing power to run the tools. These tools support coordinated analytic methods and consistent interpretation of results across laboratories. Users can create and share tools for their specific needs and use sequence data generated locally and elsewhere. Results In its first full year (2018), GalaxyTrakr processed over 85,000 jobs and went from 25 to 250 users, representing 53 different public and state health laboratories, academic institutions, international health laboratories, and federal organizations. By mid-2020, it has grown to 600 registered users and processed over 450,000 analytical jobs. To illustrate how laboratories are making use of this resource, we describe how six institutions use GalaxyTrakr to quickly analyze and review their data. Instructions for participating in GalaxyTrakr are provided. Conclusions GalaxyTrakr advances food safety by providing reliable and harmonized WGS analyses for public health laboratories and promoting collaboration across laboratories with differing resources. Anticipated enhancements to this resource will include workflows for additional foodborne pathogens, viruses, and parasites, as well as new tools and services.


2017 ◽  
Vol 23 (9) ◽  
pp. 1441-1445 ◽  
Author(s):  
Kelly F. Oakeson ◽  
Jennifer Marie Wagner ◽  
Michelle Mendenhall ◽  
Andreas Rohrwasser ◽  
Robyn Atkinson-Dunn

2013 ◽  
Vol 18 (4) ◽  
Author(s):  
K A Jolley ◽  
M C Maiden

Whole genome sequence (WGS) data are increasingly used to characterise bacterial pathogens. These data provide detailed information on the genotypes and likely phenotypes of aetiological agents, enabling the relationships of samples from potential disease outbreaks to be established precisely. However, the generation of increasing quantities of sequence data does not, in itself, resolve the problems that many microbiological typing methods have addressed over the last 100 years or so; indeed, providing large volumes of unstructured data can confuse rather than resolve these issues. Here we review the nascent field of storage of WGS data for clinical application and show how curated sequence-based typing schemes on websites have generated an infrastructure that can exploit WGS for bacterial typing efficiently. We review the tools that have been implemented within the PubMLST website to extract clinically useful, strain-characterisation information that can be provided to physicians and public health professionals in a timely, concise and understandable way. These data can be used to inform medical decisions such as how to treat a patient, whether to instigate public health action, and what action might be appropriate. The information is compatible both with previous sequence-based typing data and also with data obtained in the absence of WGS, providing a flexible infrastructure for WGS-based clinical microbiology.


Author(s):  
Amnon Koren ◽  
Dashiell J Massey ◽  
Alexa N Bracci

Abstract Motivation Genomic DNA replicates according to a reproducible spatiotemporal program, with some loci replicating early in S phase while others replicate late. Despite being a central cellular process, DNA replication timing studies have been limited in scale due to technical challenges. Results We present TIGER (Timing Inferred from Genome Replication), a computational approach for extracting DNA replication timing information from whole genome sequence data obtained from proliferating cell samples. The presence of replicating cells in a biological specimen leads to non-uniform representation of genomic DNA that depends on the timing of replication of different genomic loci. Replication dynamics can hence be observed in genome sequence data by analyzing DNA copy number along chromosomes while accounting for other sources of sequence coverage variation. TIGER is applicable to any species with a contiguous genome assembly and rivals the quality of experimental measurements of DNA replication timing. It provides a straightforward approach for measuring replication timing and can readily be applied at scale. Availability and Implementation TIGER is available at https://github.com/TheKorenLab/TIGER. Supplementary information Supplementary data are available at Bioinformatics online


Data in Brief ◽  
2020 ◽  
Vol 33 ◽  
pp. 106416
Author(s):  
Asset Daniyarov ◽  
Askhat Molkenov ◽  
Saule Rakhimova ◽  
Ainur Akhmetova ◽  
Zhannur Nurkina ◽  
...  

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lynsey K. Whitacre ◽  
Jesse L. Hoff ◽  
Robert D. Schnabel ◽  
Sara Albarella ◽  
Francesca Ciotola ◽  
...  

Author(s):  
Viola Kurm ◽  
Ilse Houwers ◽  
Claudia E. Coipan ◽  
Peter Bonants ◽  
Cees Waalwijk ◽  
...  

AbstractIdentification and classification of members of the Ralstonia solanacearum species complex (RSSC) is challenging due to the heterogeneity of this complex. Whole genome sequence data of 225 strains were used to classify strains based on average nucleotide identity (ANI) and multilocus sequence analysis (MLSA). Based on the ANI score (>95%), 191 out of 192(99.5%) RSSC strains could be grouped into the three species R. solanacearum, R. pseudosolanacearum, and R. syzygii, and into the four phylotypes within the RSSC (I,II, III, and IV). R. solanacearum phylotype II could be split in two groups (IIA and IIB), from which IIB clustered in three subgroups (IIBa, IIBb and IIBc). This division by ANI was in accordance with MLSA. The IIB subgroups found by ANI and MLSA also differed in the number of SNPs in the primer and probe sites of various assays. An in-silico analysis of eight TaqMan and 11 conventional PCR assays was performed using the whole genome sequences. Based on this analysis several cases of potential false positives or false negatives can be expected upon the use of these assays for their intended target organisms. Two TaqMan assays and two PCR assays targeting the 16S rDNA sequence should be able to detect all phylotypes of the RSSC. We conclude that the increasing availability of whole genome sequences is not only useful for classification of strains, but also shows potential for selection and evaluation of clade specific nucleic acid-based amplification methods within the RSSC.


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