Genomics at icddr,b — redefining infectious disease surveillance in Bangladesh

21 AUG 2022

The genome refers to the complete genetic code of an organism that shapes its biological functions and physical characteristics, often alongside environmental factors. The genetic code is stored in the form of a polymer called DNA, which encodes information as a series of chemical bases, represented as the letter A, T, G, and C.

Genome sciences has emerged as an indispensable tool to understand the biology and evolutionary history of living organisms. Different biological species may be identified by the DNA sequence making up their genomes, and genetic variation within species can help explain important differences between individuals and populations of the same species. For instance, a single change from C to T at a specific position of the human genome can determine whether an individual can digest lactose and thus be able to consume milk as an adult. In the microbial realm, the presence or absence of a gene — a series of bases forming a functional unit within a genome — can tell us whether the bacterium is resistant to a particular antibiotic.

 

Genome sequences allow identification and classification of different SARS-CoV-2 strains. Frequent sampling can help track the origins and spread of different strains. The circled tips in the figure represent samples from Bangladesh. Cowley et al., Nature Microbiology

The first complete genome – belonging to the bacterium Haemophilis influenzae – was published in 1995, after a massive sequencing effort that took 13 months¹. The technology to decipher the sequences of genomes has come a long way, making it possible to now sequence hundreds to thousands of bacterial and viral genomes in a single day. This complements infectious disease surveillance efforts at the local and international levels by allowing scientists to track and predict the spread of pathogenic bacteria and viruses in order to better prepare for pandemics or prevent disease outbreaks. In the face of the recent COVID-19 pandemic, genome sequencing has enabled scientists to keep pace with newly evolving SARS-CoV-2 strains.

icddr,b Genomics Centre (iGC) — established in 2015 through a generous grant from the Swedish International Development Cooperation Agency (SIDA) — has been at the forefront of SARS-CoV-2 surveillance in Bangladesh. Genomic surveillance of the virus is key to developing effective governmental policies to control its spread. For instance, the rapid rise of a new strain may call for a shift in the pandemic response strategy to anticipate possible increases in infection and hospitalization rates. Working alongside the Government of Bangladesh and other partner institutions, the iGC has helped monitor the emergence and spread of SARS-CoV-2 strains since early in the pandemic.

icddr,b’s work in infectious disease surveillance extends far beyond monitoring SARS-CoV-2, and the iGC has become integral to its surveillance of many pathogens across the country. State-of-the-art technologies — Illumina MiSeq, NextSeq, and Oxford Nanopore MinION, alongside some bioinformatics capacity — enable the iGC to perform whole-genome sequencing (WGS) of bacteria and viruses, 16s metagenomics to study microbiome composition, and shotgun metagenomics to identify genetic variants associated with specific traits.

Antibiotic-resistant pathogens are a rising public health concern that contributes to higher costs and mortality by making traditional treatments against common infections ineffective. icddr,b leads the surveillance of these pathogens in Bangladesh. The iGC helps icddr,b researchers monitor microbes at the genomic level — in a project funded by The London School of Hygiene & Tropical Medicine, UK — to identify and track genes conferring resistance to specific antibiotics. This can enable the medical community to regulate the use of different antibiotics to maximize their effectiveness.

Basic steps involved in next-generation sequencing. Adapters are chemically attached to the ends of DNA fragments to facilitate the anchoring of the fragments and to initiate sequencing.

As part of a separate project funded by the Wellcome Trust Sanger Institute, the iGC performs genome sequencing of environmental Vibrio cholerae — the causative agent of the major diarrhoeal disease cholera — to enable the study of its ecology and evolution. This can help researchers track different strains of the bacterium as they circulate or become dominant, and identify new genes associated with antibiotic resistance or severe disease.

During the 2022 cholera outbreak, our scientists were able to effectively use the iGC’s services to respond to the emergency. At a time when the icddr,b hospital was treating a record high number of diarrhoeal disease patients— more than 1400 a day — the iGC’s rapid whole-genome sequencing of patient samples allowed the scientists to characterize and identify the source of the outbreak, with lifesaving implications.

The Child Health and Mortality Prevention Surveillance (CHAMPS) project, funded by the Bill and Melinda Gates Foundation, utilizes the iGC’s genome sequencing services to investigate microbial isolates from postmortem tissue specimens of deceased stillbirths and neonates. The genomes of these microbes can help researchers identify microbial strains and their genes associated with antimicrobial resistance.

These projects represent a sampling of the many sequencing-based projects supported by that the iGC’s genome sequencing facility. Real-time genomic surveillance of circulating and emerging pathogens will help icddr,b make further major contributions to infectious disease control and other public health efforts in Bangladesh and beyond. The iGC makes its services available and accessible to scientists across icddr,b and the country, and welcomes collaboration. Its expertise in generating, processing, and analyzing genomic data provides opportunities for scientists to pursue new and exciting questions and contribute to an emerging ecosystem of genomics research in the country.