Research Roundup: March 27, 2020

Welcome to the March 27, 2020 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Broad’s Clinical Research Sequencing Platform tests COVID-19 patient samples

Broad Institute’s CLIA-certified testing center has begun processing COVID-19 patient samples and is a Massachusetts state reference lab. The facility now has capacity to process approximately 2,000 COVID-19 tests per day. Results were returned in 24 hours on the first day of processing, falling to an average 12-hour turnaround time from receipt. You can read the Broad announcement here, as well as coverage from WBUR and WCVB.

Creatures of (dietary) habit

Do our genes influence what we eat? Using survey responses and genetic data from nearly 450,000 UK Biobank participants, Joanne Cole, co-directors of the Metabolism Program and institute members Jose Florez and Joel Hirschhorn, conducted a genome-wide association study on dietary habits, looking for genetic signals related to whether someone gravitates toward healthy or unhealthy diets. Writing in Nature Communications, they report links between dietary patterns and 814 loci, including intriguing genetic relationships between fruit intake and the sense of smell, and between dietary choices, body-mass index, and educational attainment. 

A cellular view of HIV infection

A better understanding of key immune responses during the earliest stages of HIV infection could help inform future vaccine and treatment efforts. Reporting in Nature Medicine, Samuel Kazer, associate member Bruce Walker of the Infectious Disease and Microbiome Program, institute member Alex Shalek, of the Klarman Cell Observatory, and colleagues interrogated peripheral immune responses in acute HIV infection using single-cell RNA-sequencing. Sampling prior to and throughout acute infection, the authors discovered distinct lymphocyte and myeloid cell responses with similar temporal expression patterns as well as cell subsets associated with two individuals who later developed control of HIV infection without treatment. Together, their longitudinal study provides a readily applicable framework for characterizing multiple dynamic cellular responses and their interactions in health and disease.

Weak at the knees

The evolutionary adaptations that support walking upright in humans may lead to osteoarthritis in adulthood. For a look at the evolution of knee cartilage, a team led by Daniel Richard, Zun Liu (both of Harvard University), and Terence Capellini, an associate member in the Program in Medical and Population Genetics, profiled the epigenetics of joint chondrocytes, finding that ancient positive and purifying selection influenced the shape of the human knee. Reporting in Cell, they found that regulatory elements influence knee morphology and overlap with genetic risk factors for osteoarthritis. They discovered a genetic variant present in billions of people that impacts knee shape in mice and raises risk for osteoarthritis.

Probing prion prevention

Clinical trials in prion disease have been performed with patients already showing debilitating symptoms, missing the opportunity to study preventive strategies. In a Personal View in The Lancet Neurology, associated scientists Sonia Vallabh and Eric Minikel, founding core member Stuart Schreiber, and president and founding director Eric Lander outline possible designs for trials to delay or prevent prion disease arising from a genetic cause. The authors describe a proposal they made to FDA scientists for trials supporting Accelerated Approval of new drugs to treat prion disease. They provide support for using reduced prion protein load in human cerebrospinal fluid as a biomarker that likely predicts clinical benefit in individuals carrying pathogenic prion protein mutations.