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Welcome to the April 9, 2021 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Ó³»­´«Ã½ and their collaborators.

Enhancing V2F maps

GWASs have yielded thousands of genetic variants linked to disease. To help figure out the function of many of these variants, Joseph Nasser (now at Caltech), Drew Bergman, Charles Fulco (now at Bristol Myers Squibb), Philine Guckelberger (now at the Free University of Berlin), Benjamin Doughty (now at Stanford University), Eric Lander (on leave), Jesse Engreitz (now at Stanford), and colleagues used their activity-by-contact (ABC) model to build maps that connect enhancers to their target genes in 131 cell types and tissues. Using those maps, the team linked more than 5,000 GWAS signals to nearly 2,250 genes across 72 traits and diseases. The researchers also predicted which enhancers contain risk variants for inflammatory bowel disease, suggesting a possible disease mechanism. Read more in and a Ó³»­´«Ã½ story.

Stuck on spike

Peptides that bind to SARS-CoV-2's spike protein could help guide the development of new diagnostics and therapeutics. Using an affinity selection-mass spectrometry platform, Sebastian Pomplun (MIT), associate member Bradley Pentelute of the Chemical Biology and Therapeutics Science Program, and colleagues screened more than 800 million synthetic peptides for high-affinity spike binders. They found three that stick to spike more readily than human serum proteins do, and that don't bind to the ACE2 receptor on cells. These peptides could serve as the starting point for tests that directly detect virus in human samples, or for targeted antiviral drug delivery tools. Learn more in .

Summary of the NIH consortium for somatic cell genome editing

Although gene editing has the potential to treat a wide range of diseases, scientists face challenges safely and effectively implementing these technologies in humans. An NIH initiative known as the Somatic Cell Genome Editing Consortium aims to tackle these challenges to create new gene editing technologies and therapies. In a , the Consortium — including institute scientist and Director of Vector Engineering Ben Deverman and institute member Guoping Feng, both of the Stanley Center, and core institute member and the Merkin Institute for Transformative Technologies in Healthcare director David Liu— summarized their efforts to develop new gene editors, cell delivery technologies, and biological models. They also announced plans to develop a publicly-available repository of these resources and data, to be made available to researchers across the world.

A pan-cancer panoply

Scientists in the Pan-Cancer Analysis of Whole Genomes initiative characterized intra-tumor heterogeneity across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Most samples contained subclonal expansions, often with dynamic changes in mutational processes, and frequent branching relationships between subclones. The work was led by group leader Ignaty Leshchiner in the Cancer Program; Stefan Dentro, Kerstin Haase, Maxime Tarabichi, Jonas Demeulemeester, and Peter Van Loo (Francis Crick Institute); Jeff Wintersinger, Amit Deshwar, Yulia Rubanova, and Quaid Morris (University of Toronto); David Wedge (University of Manchester); Kaixian Yu (MD Anderson); and Geoff Macintyre (University of Cambridge). Read more in .

Best practices for integrating microbiome science in public health 

Understanding of the microbiome has increased dramatically in the last decade, but many questions about implementing these discoveries remain. In a new Perspective in , associate members Wendy Garrett and Curtis Huttenhower of the Infectious Disease and Microbiome Program and colleagues at the Harvard Chan Microbiome in Public Health Center propose a framework for integrating current microbiome science into population-level health research and practice. They outline guidelines for experimental design as well as scientific opportunities across epidemiology, chronic and infectious diseases, and global and environmental health. As with all burgeoning fields, the team writes, effective communication in education, outreach, and public policy will be critical to incorporating new science at scale.

To learn more about research conducted at the Ó³»­´«Ã½, visit broadinstitute.org/publications, and keep an eye on broadinstitute.org/news.