Non-coding variants cataloged & characterized, image analysis apps advance, and dysfunction dynamics in T cells
Research Roundup: September 17, 2021
Welcome to the September 17, 2021 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
Identifying causal variants in noncoding regions of the genome
Genetic variations in the 3' untranslated region (UTR), a noncoding area of mRNA that influences gene expression, are strongly associated with human traits and diseases but difficult to characterize. A team led by Dustin Griesemer, James Xue, Steven Reilly, Ryan Tewhey (The Jackson Laboratory), and institute member Pardis Sabeti developed a new assay, MPRAu (Massively Parallel Reporter Assay for 3'UTRs), to study the function of these variants. The researchers uncovered more than 2,000 3' UTR variants that modulate gene expression and nominated causal variants associated with macular degeneration, schizophrenia, lipid levels, and other diseases, showcasing the potential for this approach. Learn more in Cell and a tweetorial by Reilly.
A pair of profilers, improved
David Stirling, Allen Goodman, institute scientist Anne Carpenter, senior group leader Beth Cimini, and others in the Imaging Platform have released updates to two popular free and open-source image analysis tools. In BMC Bioinformatics, they describe CellProfiler 4, an image analysis program for processing microscopy images that now includes usability improvements, new modules, and optimizations for quicker and less costly analyses. In Bioinformatics, they present an enhanced-performance update to CellProfiler Analyst, which allows users to explore quantitative image-derived data and train machine learning classifiers. Version 3.0 is more compatible with CellProfiler 4 and improves detection and measurement of particular classes of objects.
Dynamics of T cell dysfunction
CD8+ T cells can become dysfunctional and lose their ability to kill cells, which limits anti-tumor immune responses. In Immunity, Jason Schenkel, graduate student Rebecca Herbst, core institute member Aviv Regev (on leave), senior associate member Tyler Jacks of the Cancer Program, and colleagues report the dynamics of T cell dysfunction in a mouse model of lung adenocarcinoma. They show that conventional type I dendritic cells (cDC1s) maintain a reservoir of TCF-1+ CD8+ T cells (which control the response to immunotherapies that disrupt immune checkpoints) in lymph nodes that drain the tumor. Levels of cDC1s decrease with tumor progression and contribute to failed immunity, suggesting that cDC1s could be harnessed for therapeutic applications.