Looking at rare and common heart disease variants together, antibiotic combinations' synergistic roots, sleep EEG as schizophrenia biomarker, and more
Research Roundup: May 23, 2022
Welcome to the May 23, 2022 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
Bringing rare and common heart disease risk factors together
Hypertrophic cardiomyopathy (HCM) is a leading cause of heart-related death in young people. There is evidence that rare variants have a causal role in HCM, and genome-wide association studies have identified common variants that contribute to risk, but it is unclear whether polygenic risk scores improve risk stratification. Kiran Biddinger, Sean Jurgens, institute member and Cardiovascular Disease Initiative director Patrick Ellinor, Krishna Aragam, and colleagues analyzed data from the UK and Mass General Brigham biobanks to assess contributions of rare and common genetic variation to HCM risk. They found that rare variants and polygenic risk scores were strong predictors of disease, suggesting that future genetic testing should combine both approaches. Read more in JAMA Cardiology and Krishna’s tweetorial.
How a dynamic drug duo works together
Combinations of antibiotics may prove more effective in patients with mutli-drug resistant bacterial infections than giving separate drugs individually, but the biological bases of drugs' synergistic effects are largely unknown. Alexandra Grote and institute scientist Ashlee Earl of the Genomic Center for Infectious Diseases and Infectious Disease and Microbiome Program teamed up with Beth Israel Deaconess Medical Center's Thea Brenna-Krohn, Shade Rodriguez, and James Kirby to explore the transcriptional outcomes of treating Klebsiella pneumoniae with minocycline and colistin alone and together. They report in Antimicrobial Agents and Chemotherapy that bacterial gene expression patterns suggest that colistin disrupts K. pneumoniae's outer membrane, opening the door for minocycline to deliver a killing blow.
Painting a picture of variants' roles in lung cancer
Cell Painting is an image-based morphological profiling assay developed by the labs of Imaging Platform senior director Anne Carpenter, core institute member Stuart Schreiber, and others. Schmidt Fellow Juan Caicedo, Carpenter, Imaging Platform senior group leader Shantanu Singh, and colleagues used Cell Painting to study the effects of lung cancer genetic variants in cells. By developing deep learning-based methods to analyze cell images and convert them to high-dimensional phenotypic profiles, they showed that morphological profiling could predict variants' effects and reveal biological insights at the single-cell level. The team says this method, with its low cost and ease of implementation, is a promising, non gene-specific way to systematically assess variant function. Read more in Molecular Biology of the Cell.
Sleep EEG as a window into schizophrenia
Researchers need objective biomarkers to conduct mechanistic research and therapeutic development for psychiatric disorders, as these conditions display a wide variety of clinical and genetic features. Postdoctoral scholar Nataliia Kozhemiako, institute scientist Jen Pan in the Stanley Center for Psychiatric Research, senior associate member Shaun Purcell, and collaborators comprehensively characterized multiple domains of non-rapid eye movement (NREM) sleep neurophysiology, their interdependencies, and their relationships to waking EEG and clinical features in a new cohort of 72 patients with schizophrenia and 58 healthy controls. This study highlights the importance of NREM sleep measures, and lays the groundwork for evaluating EEG biomarkers, individually or in combination, to guide diagnosis and treatment efforts. Read more in eLife and a tweetorial by Nataliia.