COVID-19 test insights, an expanded elemental encyclopedia, where food choice and genetics meet, and more.
By Broad Communications
Credit: Erik Jacobs
Welcome to the July 31, 2020 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
An encyclopedic effort
For 17 years, the Encyclopedia of DNA Elements (ENCODE) Consortium has been working to comprehensively describe the genome's functional elements: sequences representing genes, promoters, enhancers, non-coding RNAs, etc. In a new study in Nature, Charles Epstein, Noam Shoresh, institute member Bradley Bernstein, and more than a dozen others in the Epigenomics Program join more than 100 scientists globally in announcing the completion of ENCODE 3. This latest phase of ENCODE resulted in nearly 6,000 new human and mouse datasets as well as a web-based tool for visualizing the data. And in a complementary Nature Communications paper (one of 13 published across the Nature family), Nauman Javed, Shoresh, and colleagues present Crosscheck, a computational method for detecting sample annotation errors in sequencing studies. Applying Crosscheck to nearly 9,000 ENCODE datasets, they flagged about one percent of ENCODE samples as possibly having been mis-annotated. Learn more in an NHGRI press releaseandonTwitter.
Surveillance testing of nursing homes shows most who test positive for SARS-CoV-2 had no reported symptoms
In a preprint and Broadminded blog post, Niall Lennon, senior director of translational genomics and product development and institute scientist, associated scientist Roby Bhattacharyya, and colleagues describe the analysis of data from nearly 33,000 COVID-19 tests from Massachusetts nursing homes that were processed by the Genomics Platform's testing facility. They give two takeaways: first, that surveillance testing (regular testing of asymptomatic people) can effectively detect potential outbreaks among individuals without symptoms, especially in vulnerable populations; and second, that viral load distributions among those with and without symptoms at the time of testing are similar. Read more from NBC News.
Proteins on the move
Proteins on the surface of lipid droplets (LD) in the cell support lipid metabolism, but it’s unclear how they get there from the endoplasmic reticulum (ER). New clues come from work by Maria-Jesus Olarte (Yale, Harvard), Jessica Swanson (University of Utah), associate members Robert Farese, Jr. and Tobias Walther of the Harvard School of Public Health and the Broad Metabolism Program, and colleagues. The scientists utilized hydrophobic, membrane-embedded portions of two fruit fly proteins, the GPAT4 enzyme (also known as LiveDrop) and ALG14, to dissect the ER-to-LD targeting mechanism. Appearing in Developmental Cell, the study identified sequence requirements and principles underlying the accumulation of these motifs on LDs.
mTORC1 senses a sugar-sprung substance
The mTORC1 kinase regulates cell growth and requires the presence of amino acids and glucose, but how it’s activated by the latter isn’t known. Using metabolically engineered human cells lacking the canonical energy sensor AMPK, a team led by Jose Orozco and senior associate member David Sabatini of the Whitehead Institute and the Broad Cell Circuits Program showed that mTORC1 senses a glucose-derived metabolite downstream of aldolase and upstream of the GAPDH-catalysed steps of glycolysis. Reporting in Nature Metabolism (paywall), they find the key molecule to be dihydroxyacetone phosphate, a precursor for lipid synthesis (a process under mTORC1's control).
Genetic risk of obesity and food choices
The influence of genetic risk of obesity on food choice behaviors is not completely understood. However, collecting data on what employees purchase at workplace cafeterias can provide researchers with an opportunity for objective, real-time assessment of employees’ food choices. Associate member of the Program in Medical and Population Genetics Richa Saxena, Hassan Dashti, and colleagues analyzed genetic and cafeteria food purchase data from 397 employees at a large Boston hospital who enrolled in a workplace health study. InPLOS Medicine, the authors report that genetic risk for obesity was associated with the quality, quantity, and timing of workplace food purchases, and suggest that such risk may influence eating behaviors that contribute to weight.
Long live the beaver and naked mole rat
Studying long-lived rodents such as beavers and naked mole rats could shed light on the mechanisms of longevity. Xuming Zhou, associate member Vadim Gladyshev of Brigham and Women’s Hospital, and their colleagues analyzed and compared the genomes of these enduring mammals. They found widespread amino acid substitutions at “disease-causing” sites, and that both genomes share identical substitutions linked to common adaptive phenotypes such as resistance to DNA damage and cellular stress. The team also discovered signals of positive selection in energy and fatty acid metabolism pathways. This genome resource could help in the discovery of genetic factors involved in longevity and adaptive evolution. Read more in Cell Reports.
Cumulus enables scalable RNA-seq data analysis in the cloud
The rise of massively parallel single-cell and single-nucleus RNA sequencing has increased the need for new computational pipelines to analyze the resulting data. A team led by associate member Bo Li, institute scientist Orit Rozenblatt-Rosen, and core institute member and Klarman Cell Observatory director Aviv Regev has developed Cumulus, a flexible cloud-based framework for analyzing such large-scale datasets. Building on Broad DSP's Terra platform, Cumulus offers high scalability, low cost, user-friendliness, and integrated support. The team benchmarked Cumulus on a Human Cell Atlas dataset of bone marrow cells and showed that it substantially improved efficiency over conventional frameworks, while maintaining or improving the quality of results. Learn more in Nature Methods.