Data and computation are hallmarks of the newest paradigm of scientific research, and especially in this time of COVID-19, we need innovation to drive discovery. Technology is a key tool that is helping researchers work more effectively with data and support COVID data science projects. Recognizing this, Amazon Web Services (AWS) has offered their support and donated service credits provided by the AWS Diagnostic Development Initiative for cutting edge COVID-19 research at the University of California, San Francisco (UCSF). Facilitated by the UCSF Bakar Computational Health Sciences Institute, AWS connected with the laboratory of Charles Chiu, MD, PhD to enable two projects involving sequencing the genomes of the viruses infecting hundreds of COVID-19 patients in the Bay Area using CRISPR gene-technology in a clinical research study.
COVID-19 Host Transcriptome Profiling Project
Dr. Chiu and his translational research laboratory team are performing transcriptome analysis of nasal swab and whole blood samples from patients with viral respiratory infection to identify specific biomarkers of the disease. To date, they have identified distinct signatures for influenza, RSV (respiratory syncytial virus), bacterial sepsis, Lyme disease, and babesiosis. They hypothesize that COVID-19 infection evokes a specific and distinct host response in infected patients that would be detectable by RNA sequencing, and that machine learning-based models can discriminate between respiratory viral infections on the basis of the host response. Indirect diagnostic testing on the basis of the early host response may be critical to aiding rapid response efforts as recent data has suggested that SARS-CoV-2 is associated with asymptomatic infection and transmission (Chan, et al, 2020, the Lancet).
COVID-19 Viral Genomic Sequencing Project
Chui and team also developed a method (metagenomic sequencing with spiked primer enrichment, MSSPE) that will enrich metagenomic libraries for 2019-nCoV genome sequences (Deng et al, 2020, Nature Microbiology). The method is complementary to other methods of viral genome sequence recovery, and is particularly useful for analysis of nasopharyngeal swab samples with low viral concentrations. Chiu and team have leveraged this new method to conduct a genomic survey of SARS-CoV-2 strains circulating in California. They were able to demonstrate that the strain that infected people aboard the Grand Princess cruise ship clusters with the WA1 strain predominantly circulating in Washington State (Read Mercury News article). They are now collaborating with the US CDC, California Department of Public Health, and Santa Clara Department of Public Health to conduct real-time, genomic surveillance of SARS-CoV-2 infection in California. Chiu’s work, which includes tracking mutations and the spread of infection, is essential for guiding public health interventions to minimize further spread of the virus while residents are told to “shelter in place”.
“In today’s rapid-changing environment around the COVID-19 pandemic, cloud computing resources will accelerate our efforts to design the next-generation of diagnostic tests and provide real-time, actionable genomic data to inform the public health response” says Charles Chiu, MD, PhD.