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A study of more than 150,000 people has uncovered more than 70 genes that are strongly associated with autism, several for the first time, and hundreds of genes linked to neurodevelopmental conditions. The results reveal diverse forms of protein-coding variation in autism and shed light on the molecular roots of brain development and neurodiversity. The findings result from an international collaboration by scientists at Broad, including the Stanley Center; Icahn School of Medicine at Mount Sinai; Massachusetts General Hospital; University of California, San Francisco; and University of Pittsburgh School of Medicine. The datasets were derived from the Autism Sequencing Consortium (ASC), the Simons Foundation Powering Autism Research (SPARK) initiative, the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), and the Center for Common Disease Genomics (CCDG) at the Broad. The study is one of four in Nature Genetics using some of the same data to explore the genetic basis of autism.
Researchers have developed a smartphone app that helps users model viral outbreaks, using Bluetooth to “spread” a virtual human virus to nearby participating phones. Users can scan QR codes to use interventions such as vaccines, diagnostic tests, masks, or hazmat suits, and the app records data scientists can use to map how a virus spreads. “Our ultimate goal is to create a simulation software that anyone can easily use to coordinate a simulation whenever they want,” said Ivan Specht, a Harvard University undergraduate researcher and first author on the study. “We envision a world where Operation Outbreak is deployed at least once in every school, because we think that children everywhere should get access to at least some level of outbreak science education.”
The gut microbe Akkermansia muciniphila has been strongly associated with positive systemic effects on host metabolism. Broad and Harvard Medical School researchers have identified a novel lipid from the bacteria’s cell membrane, revealed its molecular structure, and discovered that it binds to specific receptors on immune cells, resulting in the release of certain immune-stimulating cytokines. The team also revealed how a single molecule and microbial chemistry help moderate immune responses, and suggests that their findings could inspire new therapeutics.
When they sequenced the human genome, researchers from the Human Genome Project identified about 20,000 genes using a set of rules. But some scientists think those rules excluded important sequences. A new effort to catalog what some call the “dark matter of the human genome” — oft-missed regions of protein translation called noncanonical open reading frames (ORFs) — could yield insights into disease and what makes humans unique. Read more in a Q&A with Broad postdoctoral researcher John Prensner, who co-founded the consortium leading this effort.
We are thrilled to welcome Erin Chen and Sam Peng as core institute members. Core institute members have their primary laboratories at the Broad Institute and have academic appointments at Massachusetts Institute of Technology (MIT), Harvard University, or one of Harvard’s primary teaching hospitals. They are deeply engaged in the intellectual life of the Broad and help set the institute’s scientific direction. Joining in January 2023, Erin will be an assistant professor at MIT Department of Biology and an attending dermatologist at Massachusetts General Hospital. Sam joined this month and is an assistant professor at MIT Department of Chemistry. “These creative scientists are each taking inventive approaches to understand the molecular signals and interactions that underlie biological processes in health and disease,” said Todd Golub, director of the Broad. “These insights will help further the Broad’s mission of advancing the understanding and treatment of human disease.”
Heart failure is one of the most common causes of hospitalization in the United States. According to cardiologist Patrick Ellinor, almost all forms of heart failure are treated similarly, no matter their cause. New single-cell maps of gene expression in two major causes of heart failure — dilated and hypertrophic cardiomyopathy — suggest cell types and biological mechanisms that could be the targets of new treatments.
A new computer model can predict dominant SARS-CoV-2 variants and could serve as an early warning system in the future. The model, called PyR0, is capable of analyzing millions of genomes in about an hour. When tested on viral genomic data from January 2022, it correctly predicted the rise of the BA.2 variant, which became dominant in many countries in March 2022. PyR0 would have also identified the B.1.1.7 variant by late November 2020, a month before the World Health Organization listed it as a variant of concern.
Urinary tract infections (UTIs) are common among females, with a quarter of UTI sufferers experiencing repeated infections. Researchers have thought that higher levels of E. coli bacteria in the intestines of some people may be contributing to recurrent UTIs, but a new study led by scientists at the Broad and Washington University in St. Louis points to other possible causes, including different immune system responses and imbalances in the gut’s microbial makeup, or the microbiome.
Scientists in the Eric and Wendy Schmidt Center have built a new machine learning framework for addressing complex matrix completion tasks. The work is the first to be published by the Schmidt Center, launched at the Broad in 2021. Based on infinitely large neural networks, the method is simple, fast, and flexible, and can be easily deployed on a standard laptop for a range of tasks. The researchers demonstrated the method by performing virtual drug screening using Connectivity Map data and filling in missing areas of digital images, with proficiency rivaling more computationally costly methods.
We spoke with Morgan Sheng, co-director of the Stanley Center for Psychiatric Research, about the significance of the SCHEMA findings for new drug development for schizophrenia. Here’s an excerpt: “I’m excited because, with the SCHEMA genes, all of a sudden schizophrenia has a bunch of actionable genes that we can really dig deep into — and some of them are even druggable targets. For SCHEMA genes that are not immediately targetable by a drug, if we understand more about the mechanism by which they cause schizophrenia, we can find promising targets for therapeutic intervention.”
