Moving pathogen genomics out of the lab and into the clinic: what will it take?

Luheshi, Leila M.; Raza, Sobia; Peacock, Sharon J.

doi:10.1186/s13073-015-0254-z

Cited by 10 publications

(12 citation statements)

References 9 publications

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“…With advancements in the speed, throughput, and cost of genome sequencing, population analyses of infectious disease outbreaks in the public health sector (primarily foodborne) are routinely driven by whole-genome sequencing ( 10 ). Such methodologies offer unprecedented resolution in determining outbreak sources and transmission pathways when quality sampling and epidemiological data are integrated in the study design ( 11 ).…”

Section: Commentarymentioning

confidence: 99%

Straight from the Horse’s “Mouth”: Genomic Epidemiology of an Icelandic Equine Epidemic

Davies

2017

mBio

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Despite tight biosecurity measures, an outbreak of respiratory disease rapidly spread across the Icelandic equine population in 2010. Horse transportation was brought to a halt in order to contain the spread of the infectious agent. In a recent article, Björnsdóttir and colleagues (S. Björnsdóttir et al., mBio 8:e00826-17, 2017, https://doi.org/10.1128/mBio.00826-17) employ the power and resolution of “genomic epidemiology,” the combination of whole genomic sequencing and epidemiological approaches, to examine the source and spread of the outbreak. Intriguingly, the outbreak was not viral in origin, but linked to a bacterial “commensal” Streptococcus equi subsp. zooepidemicus infection. A national sampling strategy coupled with population genomics revealed that the outbreak was most likely driven by a S. equi subsp. zooepidemicus sequence type 209 (ST209) infection that spread nationally from a single source. This retrospective study demonstrates the power of genomics applied on a national scale to unravel the cause of a significant biosecurity threat.

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Section: Commentarymentioning

confidence: 99%

Straight from the Horse’s “Mouth”: Genomic Epidemiology of an Icelandic Equine Epidemic

Davies

2017

mBio

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“…Notwithstanding its promises, several challenges remain for the adoption of WGS in microbiology laboratories [19–22]. The accelerated obsolescence of the sequencing platforms presents several obstacles in bridging the gap between research and routine diagnostics including standardizations efforts [23]. The downstream bioinformatics pipelines are also unique challenges for the microbiology laboratory both in terms of infrastructure and skilled operators [24–27].…”

Section: Introductionmentioning

confidence: 99%

Validation and Implementation of CLIA-Compliant Whole Genome Sequencing (WGS) in Public Health Laboratory

Truong²,

Greninger³

et al. 2017

Preprint

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BackgroundPublic health microbiology laboratories (PHL) are at the cusp of unprecedented improvements in pathogen identification, antibiotic resistance detection, and outbreak investigation by using whole genome sequencing (WGS). However, considerable challenges remain due to the lack of common standards.Objectives1) Establish the performance specifications of WGS applications used in PHL to conform with CLIA (Clinical Laboratory Improvements Act) guidelines for laboratory developed tests (LDT), 2) Develop quality assurance (QA) and quality control (QC) measures, 3) Establish reporting language for end users with or without WGS expertise, 4) Create a validation set of microorganisms to be used for future validations of WGS platforms and multi-laboratory comparisons and, 5) Create modular templates for the validation of different sequencing platforms.MethodsMiSeq Sequencer and Illumina chemistry (Illumina, Inc.) were used to generate genomes for 34 bacterial isolates with genome sizes from 1.8 to 4.7 Mb and wide range of GC content (32.1%-66.1%). A customized CLCbio Genomics Workbench - shell script bioinformatics pipeline was used for the data analysis.ResultsWe developed a validation panel comprising ten Enterobacteriaceae isolates, five gram-positive cocci, five gram-negative non-fermenting species, nine Mycobacterium tuberculosis, and five miscellaneous bacteria; the set represented typical workflow in the PHL. The accuracy of MiSeq platform for individual base calling was >99.9% with similar results shown for reproducibility/repeatability of genome-wide base calling. The accuracy of phylogenetic analysis was 100%. The specificity and sensitivity inferred from MLST and genotyping tests were 100%. A test report format was developed for the end users with and without WGS knowledge.ConclusionWGS was validated for routine use in PHL according to CLIA guidelines for LDTs. The validation panel, sequencing analytics, and raw sequences will be available for future multi-laboratory comparisons of WGS in PHL. Additionally, the WGS performance specifications and modular validation template are likely to be adaptable for the validation of other platforms and reagents kits.

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“…Collating, integrating and sharing data at scale and across the complex ecosystem of people and organizations involved in the management of infectious diseases does not come without huge technological, operational, political, ethical and regulatory challenges. As part of our review of what it will take to bring pathogen genomics into mainstream clinical and public health practice ( Luheshi et al , 2015 ), we consulted with multidisciplinary experts in the field to consider the factors most pertinent to the development of a data integration and management strategy. These discussions informed our vision for a data integration model which we believe can serve to maximize both the immediate and the future benefits of pathogen genomics if adopted by nations investing in this technology.…”

Section: Introductionmentioning

confidence: 99%

Big data or bust: realizing the microbial genomics revolution

Raza

Luheshi

2016

Microbial Genomics

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Pathogen genomics has the potential to transform the clinical and public health management of infectious diseases through improved diagnosis, detection and tracking of antimicrobial resistance and outbreak control. However, the wide-ranging benefits of this technology can only fully be realized through the timely collation, integration and sharing of genomic and clinical/epidemiological metadata by all those involved in the delivery of genomic-informed services. As part of our review on bringing pathogen genomics into ‘health-service’ practice, we undertook extensive stakeholder consultation to examine the factors integral to achieving effective data sharing and integration. Infrastructure tailored to the needs of clinical users, as well as practical support and policies to facilitate the timely and responsible sharing of data with relevant health authorities and beyond, are all essential. We propose a tiered data sharing and integration model to maximize the immediate and longer term utility of microbial genomics in healthcare. Realizing this model at the scale and sophistication necessary to support national and international infection management services is not uncomplicated. Yet the establishment of a clear data strategy is paramount if failures in containing disease spread due to inadequate knowledge sharing are to be averted, and substantial progress made in tackling the dangers posed by infectious diseases.

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Moving pathogen genomics out of the lab and into the clinic: what will it take?

Cited by 10 publications

References 9 publications

Straight from the Horse’s “Mouth”: Genomic Epidemiology of an Icelandic Equine Epidemic

Straight from the Horse’s “Mouth”: Genomic Epidemiology of an Icelandic Equine Epidemic

Validation and Implementation of CLIA-Compliant Whole Genome Sequencing (WGS) in Public Health Laboratory

Big data or bust: realizing the microbial genomics revolution

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