We are actively leading consortia to develop methods for sequence-based association studies of all coding and noncoding functional annotations in the genome.

The NHGRI AnVIL (Genomic Data Science Analysis, Visualization, and Informatics Lab-space) is a project powered by Terra for biomedical researchers to access data, run analysis tools, and collaborate.

The Centers for Common Disease Genomics are a collaborative large scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes such as cardiovascular diseases (early-onset cardiovascular disease, atrial fibrillation, hemorrhagic stroke), neuropsychiatric diseases (autism, Alzheimer’s disease, epilepsy), and immune-mediated diseases (irritable bowel disorder, asthma, Type-1 diabetes). The Broad Institute is one of four selected CCDG project centers. The Talkowski lab focuses on neuropsychiatric disease (autism, Alzheimer’s disease, epilepsy).

The CommonMind Consortium is a public-private partnership bringing together area knowledge, large scale and well-curated brain sample collections, data management and analysis expertise. The consortium has a goal to generate and analyze large-scale genomic data from human subjects with neuropsychiatric disease and to make these data and the associated analytical results broadly available to qualified investigators.

The Center for Mendelian Genomics (CMG) at the Broad Institute, led by Drs. Daniel MacArthur, Heidi Rehm, and Anne O’Donnell-Luria, is a part of the Mendelian Genomics Research Consortium and aims to discover new genes that underlie Mendelian disease. Dr. Talkowski’s lab will assist with data analyses and gene discovery, with a particular focus on structural variation.

The Genome Aggregation Database (gnomAD), is a coalition of investigators seeking to aggregate and harmonize exome and genome sequencing data from a variety of large-scale sequencing projects, and to make summary data available for the wider scientific community. The project is overseen by co-directors Heidi Rehm and Mark Daly, and council members Daniel MacArthur, Benjamin Neale, Michael Talkowski, Anne O’Donnell-Luria, Grace Tiao, Matthew Solomonson, and Kat Tarasova. In its first release, which contained exclusively exome data, it was known as the Exome Aggregation Consortium (ExAC).

The NHGRI Genome Sequencing Program (GSP) uses genome sequencing to identify genes and genomic variants underlying human inherited disease across its full spectrum, including rare diseases likely to be due to rare variants with strong effects (Mendelian), and common genetically complex diseases that are caused by many variants. Novel methods, tools, and knowledge gained through the GSP will be rapidly shared to enhance the ability of the community to pursue other human inherited diseases.

Other components of the GSP that the Talkowski lab is involved in are the Centers for Mendelian Genomics (CMG) and the Centers for Common Disease Genomics (CCDG).

The HGSVC aims to define a high-quality map of structural variation and develop new methods to take advantage of the burgeoning array of genomics assays now available to define genomic structure, including long reads, chromatin confirmation assay, strand sequencing and synthetic read and read cloud technologies.

The IHCC aims to create a global platform for translational research – informing the biological and genetic basis for disease and improving clinical care and population health.

The Psychiatric Genomics Consortium is one of the largest and most innovative and productive experiments in the history of psychiatry. The central idea of the PGC is leverage global collaboration to advance genetic discovery of biologically, clinically, and therapeutically meaningful insights. The PGC studies 11 psychiatric disorders including ADHD, Alzheimer’s disease, autism, bipolar disorder, eating disorders, major depressive disorder, obsessive-compulsive disorder/Tourette syndrome, post-traumatic stress disorder, schizophrenia, substance use disorders, and all other anxiety disorders.

The Simons Simplex Collection (SSC) is a core project and resource of the Simons Foundation Autism Research Initiative (SFARI). The SSC achieved its primary goal to establish a permanent repository of genetic samples from 2,600 simplex families, each of which has one child affected with an autism spectrum disorder, and unaffected parents and siblings. The Talkowski lab is spearheading Project 3 which will define the mutational spectrum of structural variation associated with ASD risk.