Quelling eager synpase eaters, making variant interpretation less variable, genomics for outbreak control, and more.
Research Roundup: October 19, 2018
Welcome to the October 19, 2018 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
Guarding against glial gluttons
The brain’s microglial cells regulate cellular connections by “eating” some synapses and leaving others alone. A team led by institute member Beth Stevens of the Stanley Center for Psychiatric Research and colleagues at Boston Children’s Hospital found that microglia distinguish between these synapses by detecting immune molecules known as “don’t eat me” signals at synapses. In Neuron, they describe how the interaction of CD47 molecules at synapses with the microglial SIRP-alpha receptor prevent the removal of certain neuronal connections as synapses are refined during development. The work demonstrates that protective signals are critical for normal brain development.
Removing variation from variant interpretation
While it’s fairly easy to find a variant in a patient's genome, saying what that variant means can be challenging, as there's still subjectivity in the application of current standards for clinically interpreting genetic test results. Human Mutation recently released a special issue devoted to ClinGen and ClinVar, two efforts that support the sharing of variant knowledge and the development of standards and consensus in variant interpretation. Learn more in an NHGRI press release and in a Broad Q&A, in which Heidi Rehm, an institute member in the Program for Medical and Population Genetics and leader of the Broad's ClinGen team, talks about the efforts’ impacts to date, how far variant interpretation has come, and what she thinks the future holds.
Un-MASC-ing disease-driving cells
Single-cell genomic technologies give scientists an unprecedented window into complex tissues’ cellular makeup, revealing unseen cell populations. However, pinpointing populations (especially rare ones) related to a disease of interest remains challenging. To clear things up, Chamith Fonseka and associate member Soumya Raychaudhuri at Brigham and Women's Hospital and colleagues developed MASC (Mixed-effects Association of Single Cells), a statistical method that tests cell populations' association with disease. They show in Science Translational Medicine that the method addresses technical and biological variability that mask disease-related cell types, and use it to discover a heretofore unrecognized T cell subtype involved in rheumatoid arthritis.
Looking back at Lassa
Earlier this year, a team led by Katherine Siddle, Bronwyn MacInnis, and institute member Pardis Sabeti — all of the Infectious Disease and Microbiome Program — teamed up with colleagues in Nigeria and elsewhere to rapidly sequence samples of Lassa virus during an outbreak. Real-time genomic data about the virus was crucial to helping local public health officials make management decisions. The speed and precision of the response was enabled by local laboratory infrastructure — a result of years of collaborative effort between these teams to support and train Nigerian scientists. This week, the researchers published their data in the New England Journal of Medicine. Read more in news releases from Broad and the National Institute of Allergy and Infectious Disease.
Cancer-linked BAF complexes become less BAFfling
Approximately 20 percent of all human cancers involve mutations in a group of proteins called BAF, a complex that is also linked to intellectual disability and autism spectrum disorders. However, little has been known about the structure of these complexes and how they contribute to disease. Now, a team of researchers, led by Nazar Mashtalir and institute member and Epigenomics Program co-director Cigall Kadoch, provides a detailed blueprint of how the individual parts of this key protein complex fit together, an insight that could lead to advances in drug discovery. Read more in Cell and this Broad news story.