Research Roundup: August 17, 2018

Welcome to the August 17, 2018 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Predicting disease risk from millions of variants

In Nature Genetics, institute member, Cardiovascular Disease Initiative co-director, and Program in Medical and Population Genetics co-director Sekar Kathiresan, Amit Khera, Mark Chaffin and colleagues describe how polygenic risk scores can identify large fractions of the population at high risk of developing serious common diseases. The polygenic scores use information from millions of places in the genome to ascertain risk for coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel disease, or breast cancer — identifying the likelihood of developing a deadly condition potentially before any symptoms appear.  Learn more in a Broad news story and media coverage in The New York Times, WBUR, and Associated Press. All data comprising risk scores are available to researchers via the Cardiovascular Disease Knowledge Portal.

Dietary dials for gut microbe transplants

One of the major challenges in microbiome transplants and other kinds of microbial manipulations in the gut is getting introduced bacteria to colonize or engraft. In Cell Reports, a team led by Sean Kearney and institute member Eric Alm of the Broad Infectious Disease and Microbiome Program and MIT show that they can encourage a transplanted bacterial species to 'take' in a mouse by also feeding the mouse a food — in this case, seaweed — that the species can use but that the remainder of the gut microbiome cannot. Their findings suggest that it could be possible to tune microbiome transplant engraftment by tuning the recipient's diet.

Sloppy splicing creates cancer vaccine opportunity

Cancer vaccines leverage tumor-specific peptides, called neoantigens, to get a patient's immune system to recognize, rally against, and attack their cancer. However, not all tumor neoantigens are distinct enough for the immune system to pick them up. In Nature Biotechnology, Alicia Smart, Claire Margolis, Broad Cancer Program associate member Eliezer Van Allen, and colleagues revealed a new class of neoantigens, called retained intron neoantigens, that arise because tumors often do not splice introns (short segments of noncoding DNA nestled within genes) out of their messenger RNAs properly. Learn more in a Broad news story.

Identifying the genetic drivers of thyroid cancer

Hurthle cell carcinoma (HCC) is a type of thyroid cancer marked by increased mitochondria and is resistant to radioiodine therapy. To uncover HCC’s molecular origin a research team led by the director of Broad’s Cancer Genome Computational Analysis Group and institute member Gad Getz, co-director of the Metabolism Program and institute member Vamsi Mootha, postdoctoral scholar Raj Gopal, associated scientist Kirsten Kubler, and colleagues performed whole-exome sequencing of HCC tumors and identified recurrent mutations. The researchers also reported widespread chromosomal losses and mitochondrial DNA alterations as the main drivers of HCC, in this study published in Cancer Cell.

To learn more about research conducted at the Broad, visit broadinstitute.org/publications, and keep an eye on broadinstitute.org/news.