Broad Institute of MIT and Harvard’s Post

To better support research of underrepresented populations, Zan Koenig, Mary Yohannes, Alicia Martin, and colleagues produced a new easily accessible resource that includes a set of high-quality genomes of diverse ancestry. The team jointly called variants from more than 4,000 whole genomes from 80 populations in the Human Genome Diversity Project and 1000 Genomes Project using data from gnomAD, resulting in 153 million single-nucleotide variants, indels, and structural variants. They performed a detailed ancestry analysis of the data set, demonstrated its improvements over prior versions, and offered tutorials for users of the new resource. Read more in Genome Research. https://lnkd.in/dW5Qrpnw #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Women face greater risk from cardiovascular disease than men for reasons that aren’t fully understood, and existing polygenic scores to predict risk perform worse in women than in men. Kaavya Paruchuri, Pradeep Natarajan, and colleagues built a new polygenic score that incorporates alleles exhibiting differential effects on risk for women than men. Using data from the CARDIoGRAMplusC4D analysis, their score helped improve prediction among women younger than 55, with some sex-based disparities still present. The work underscores the ongoing need to bridge the performance gap in polygenic risk prediction for coronary artery disease. Read more in the Journal of the American Heart Association. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Researchers at Whitehead Institute and Broad have developed a gene-silencing tool, CHARM, that turns off the gene causing prion diseases and could pave the way for new gene therapies for these fatal conditions. In mice, the epigenetic editing technology eliminated more than 80% of the prion protein in the brain. Read more about the journey from research to potential therapy. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

The risk of coronary artery disease (CAD) can change over a person’s lifetime, and current methods of estimating CAD risk don’t incorporate new information over time. Sarah Urbut, Pradeep Natarajan, and colleagues have developed MSGene, a model that accounts for longitudinal data, clinical covariates, and CAD polygenic risk scores to estimate transitions between 10 cardiometabolic states. The team used MSGene to analyze longitudinal data from more than 480,000 UK Biobank participants and found that it improved risk predictions compared to other risk scores. The findings, in Nature Communications, highlight the potential public health value of more accurate lifetime CAD risk estimation. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Research over the last decade has found links between the gut microbiome and risk for type 2 diabetes, which affects half a billion people worldwide. In the largest and most diverse study yet of the microbiome and type 2 diabetes, a Brigham and Women's Hospital, Harvard T.H. Chan School of Public Health, and Broad team found that the presence of specific viruses and genetic variants within bacteria correspond with T2D risk. #Microbiome #T2D #Type2Diabetes #Type2DiabetesResearch #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Fewer than one percent of people who get the flu every year get tested in part because most tests require trained personnel and expensive equipment. Now researchers have developed a low-cost paper strip test that could allow more patients to find out which type of flu they have and get the right treatment. The test uses CRISPR to distinguish between the two main types of seasonal flu (influenza A and B) as well as seasonal flu subtypes and can identify strains that resist antiviral treatment. With further work, it could potentially detect swine and avian flu strains, including H5N1, currently infecting cattle. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch #CRISPR #CRISPRResearch

About half of cancer patients treated with chimeric antigen receptor (CAR) T cell therapy do not respond to treatment, or relapse after treatment because of tumor resistance to apoptosis or poor CAR T cell persistence. To address this, Felix Korell, Tony Letai, Marcela Maus, and colleagues developed CAR T cells that overexpressed different proteins from the Bcl-2 family, which are known to protect cells against apoptosis. They found that overexpressing the Bcl-xL protein improved CAR T cell persistence and function in mouse models of lymphoma and leukemia, suggesting strategies for improving CAR T cell therapies alone and in combination with other cancer therapeutics. Read more in Science Translational Medicine. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

New research shows that an important part of CRISPR screens called CRISPR guides do not perform equally well in cells from people of all ancestries, which could cause experiments to miss potential new drug targets. “CRISPR is used ubiquitously in preclinical research, but only a minority of researchers are thinking carefully about the specific germline and ancestries that relate to their model systems,” said Jesse Boehm, a co-senior author on the study recently published in Nature Communications. “This is a warning call for the community that functional genomics is not immune to ancestry bias, and a source of opportunity to look more closely at this kind of data.” #BroadInstitute #Science #ScienceNews #Research #ScientificResearch #CRISPR #CRISPRNews

Clare Malone, Nathaniel Mabe PharmD, PhD, Alexandra Forman, Gabriela Alexe, Kim Stegmaier, and colleagues uncovered a protein complex that drives growth of the high-risk pediatric cancer neuroblastoma. Roughly a quarter of childhood neuroblastomas carry amplifications in the gene for the transcription factor MYCN, but targeting it directly is difficult. Through DepMap functional screens, the researchers found that the KAT module of the SAGA protein complex regulates both expression of the MYCN program and tumor growth. Impairing the acetyltransferase activity of the SAGA complex diminished neuroblastoma cell growth, suggesting a new therapeutic approach. Read more in Science Advances. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Researchers have linked various pathogenic cell states to inflamed synovial tissue in rheumatoid arthritis (RA). To understand the epigenetic regulation of these states, Kathryn Weinand, Soumya Raychaudhuri, and colleagues studied open chromatin in single cells in 30 synovial tissue samples, with 12 samples having multimodal transcriptional data. They found 24 chromatin classes and predicted associated transcription factors. In Nature Communications, they proposed that these classes are ‘superstates’ that encompass multiple cell states and identified classes that may mediate the effects of putative causal variants in RA. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch