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Chan Zuckerberg Biohub Aims to Enable Infectious Disease Sequencing Globally

SAN FRANCISCO (GenomeWeb) – At the American Society of Microbiology's annual Microbe conference here over the weekend, Joe DeRisi, co-president of the Chan Zuckerberg Biohub, said that with funding from the Bill and Melinda Gates Foundation the Biohub has awarded grants to research groups in 10 countries to begin implementing metagenomic sequencing for infectious diseases.

Grants were awarded to research groups in Bangladesh, Brazil, Cambodia, Kenya, Malawi, Nepal, Pakistan, South Africa, The Gambia, and Vietnam. Starting next month, researchers from the respective teams will come to the University of California, San Francisco to receive training in a metagenomic sequencing protocol. In addition, they will also receive sequencing equipment and reagents, as well as bioinformatics support, DeRisi said.

The Biohub team has developed a cloud-based, open-source pipeline for pathogen detection and surveillance called ID-seq, and DeRisi said that the team sought funding from the Gates Foundation to work with groups around the world following a successful pilot project in Bangladesh.

In collaboration with a team led by Senjuti Saha, a clinical microbiologist at the Child Health Research Foundation in Dhaka, Bangladesh, the researchers began implementing metagenomic sequencing of cerebrospinal fluid to understand the cause of meningitis.

DeRisi said that meningitis is a major cause of death in children in Bangladesh, but the underlying cause of meningitis is unknown in the majority of cases. Researchers at the Biohub had been developing a research version of a metagenomic NGS test for cerebrospinal fluid that is now being implemented clinically at the University of California, San Francisco, and they thought that the pipeline could help Saha's team. Saha came to the Biohub where she learned how to run the test and use the ID-seq pipeline, and launched a pilot study back in Dhaka.

The team described the results of the 91-person pilot in a preprint posted on the BioRxiv server in March. They ran the ID-seq pipeline on cerebrospinal fluid from 36 positive control samples with known neurologic infection, 30 samples without infection, and 25 cases of unexplained meningitis.

DeRisi described one particular case in which ID-seq identified chikungunya virus in the CSF sample of a five-day-old neonate who had unexplained meningitis, which was subsequently confirmed. The ID-seq pipeline also includes de novo assembly, DeRisi said, so the researchers were able to assemble the whole genome of the chikungunya virus and do phylogenetic analysis.

The researchers found that the chikungunya genome was more than 99 percent similar to a strain that had originated in Pakistan and caused a febrile outbreak in Dhaka in the summer of 2017. Chikungunya was also found in two other individuals in the study who had had unexplained meningitis. Sequencing and phylogenetic analysis found that all three chikungunya genomes were highly similar to each other and to the 2017 strain that had caused the febrile outbreak.

So, the researchers wondered whether the virus had also caused additional cases of meningitis. When they went back and examined 472 cerebrospinal fluid samples that had been collected during the summer of 2017, they found an additional 17 cases. While chikungunya has increasingly been reported to be associated with neurological illnesses, such cases had not previously been identified in Bangladesh, so the finding could help inform future policy decisions.

DeRisi said that the 10 new projects will begin kicking off next month as researchers start coming to San Francisco for training. The projects run the gamut of infectious disease research and include pathogen discovery, research on vector-borne disease, neonatal sepsis, zoonotic transmission, antimicrobial resistance, and uncovering causes of unexplained childhood mortality.

The goal is for "training and open-access platforms like ID-seq [to make metagenomic sequencing] globally accessible," DeRisi said.

In addition, he said, he hoped the research groups using ID-seq would use it as a means to share their data with other microbiology researchers. "It's something that doesn't routinely happen, but should," he said, and would be critical if researchers wanted to stop the spread of emerging pathogens.