Overcoming Data Bottlenecks In Genomic Pathogen Surveillance

Abstract

Performing whole genome sequencing (WGS) for the surveillance of antimicrobial resistance (AMR) offers the ability to determine not only the antimicrobials to which rates of resistance are increasing, but also the evolutionary mechanisms and transmission routes responsible for the increase at local, national, and global scales. To derive WGS-based outputs, a series of processes are required, beginning with sample and metadata collection, followed by nucleic acid extraction, library preparation, sequencing, and analysis. Throughout this pathway there are many data-related operations required (informatics) combined with more biologically-focused procedures (bioinformatics). For a laboratory aiming to implement pathogen genomics, the informatics and bioinformatics activities can be a barrier to starting on the journey; for a laboratory that has already started, these activities may become overwhelming. Here we describe these data bottlenecks and how they have been addressed in laboratories in India, Colombia, Nigeria, and the Philippines, as part of the NIHR Global Health Research Unit on Genomic Surveillance of AMR. The approaches taken include the use of reproducible data parsing pipelines and genome sequence analysis workflows, using technologies such as Data-flo, the Nextflow workflow manager, and containerization of software dependencies. By overcoming barriers to WGS implementation in countries where genome sampling for some species may be underrepresented, a body of evidence can be built to determine the concordance of antimicrobial sensitivity testing (AST) and genome-derived resistance, novel high-risk clones can be discovered, and unknown mechanisms of resistance discovered.

Establishing a national reference laboratory for antimicrobial resistance using a whole-genome sequencing framework: Nigeria’s experience

“…The unit had the advantage of having piloted the approach in the Philippines through a previous 'See and Sequence' AMR genomic surveillance initiative [5] and the proposal was written at the time Nigeria was finalizing its National Action Plan, making it possible for us to weave in genomic surveillance from inception. The award and its implementation provided equipment and consumables to get started, expertise and staff development to initiate the task of genomic surveillance, bioinformatics pipelines and data visualization tools, as well as assistance in good financial grant practices [18][19][20][21]. Additionally, because this network comprised scientists using genomic surveillance in other LMIC health systems, it was able to provide 'south-south' operational expertise.…”

A schema for digitized surface swab site metadata in open-source DNA sequence databases

“…Regulatory environmental monitoring activities involve the collection of surface swabs within built environments followed by evaluation of infectious pathogens collected on the swabs [2,3]. The metadata that describe these swab site locations provides context for pathogen isolation source and must provide sufficient detail to be actionable [4][5][6]. In addition to contextualizing data from individual samples, environmental monitoring metadata enables large collections of genomic data to be shared and integrated through digital networks [7].…”

Circulation of Third-Generation Cephalosporin Resistant Salmonella Typhi in Mumbai, India

“…The evidence of persistent transmission of this high-risk lineage in a location with high burden of typhoid fever calls for active surveillance and effective prevention measures to avert a large outbreak and international dissemination, as seen with XDR S. Typhi carrying the ESBL gene bla CTX-M-15 in an IncY plasmid in neighboring Pakistan [ 5 ]. Through technology transfer and capacity building, the Central Research Laboratory at KIMS, Bangalore, is now equipped to carry out whole genome sequencing [ 22 ] and bioinformatics analysis [ 23 ] locally to support genomic surveillance.…”