Broad Institute of MIT and Harvard

Open-source image analysis tools do an amazing job of generating image-based profiles from large-scale, high-content microscopy datasets, but don't typically perform the processing steps that prepare those profiles for the downstream analyses that provide insights into fundamental biological processes or therapeutic development. Shantanu Singh, Beth Cimini, Niranj Chandrasekaran, and members of Broad's Imaging Platform partnered with Erik Serrano, Gregory Way, and others from the University of Colorado to develop Pycytominer, an open-source Python package that automates those profile processing steps, supports both single-cell aggregate analyses, and works with a variety of image data inputs. Learn more in Nature Methods. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Genetic studies in mice and humans point to the protein ANGPTL3 as an important regulator of lipoprotein metabolism, but how it does so has been unclear. Using in vitro and in vivo approaches, Taylor Hanta Nagai (Massachusetts General Hospital), Yu-Xin Xu, members of Broad's Metabolomics Platform, and collaborators have found that ANGPTL3 teams up with SMARCAL1, a chromatin regulator, to control lipid gene expression and triglyceride storage within cells. Writing in Scientific Reports, they suggest that ANGPTL3 and SMARCAL1 might work together to help cells respond to different growth conditions, and may play key roles in energy storage and trafficking. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Check out our new collaboration with Illumina! We are proud to support a collaborative effort between Illumina and Broad Institute of MIT and Harvard's Spatial Technology Platform (STP) by providing sequencing services for the recently announced Spatial Flagship Project utilizing Illumina’s new spatial technology. The project aims to generate large-scale spatial datasets from hundreds of samples, provided by Broad Institute investigators and external research groups through an early access program as part of the STP pipeline. We look forward to supporting the advancement of spatial analysis at an unprecedented scale! Learn more about this unique program: https://bit.ly/4kC4lqy #SpatialAnalysis #Sequencing #SpatialBiology #Biotech

In case you missed the news– we have teamed up with Illumina to rapidly scale single-cell solutions! Combining Illumina’s Single Cell Prep, NovaSeq™ X Plus Platform, 25B flow cell, and DRAGEN™ analysis software workflow, with our cutting-edge Perturb-seq, CRISPR screens, and other platforms, we aim to streamline and accelerate the creation of a 5 billion single-cell atlas within the next 3 years to advance single-cell discovery. Read more about this exciting new collaboration: https://prn.to/3QZ0o1y #SingleCell #Sequencing #Bioinformatics

A massive GWAS analysis involving more than 150,000 people with heart failure uncovered 66 genetic risk factors, including 37 new ones. The work was led by Patrick Ellinor, Ramachandran Vasan (Boston University), Gustav Smith (Gothenburg University), Hilma Holm (deCODE/Amgen), Sonia Shah (U. Queensland), Quinn Wells (Vanderbilt University), and, from University College London, Albert Henry, Aroon Hingorani, and Thomas Lumbers. The researchers predicted effector genes for each locus, and further analysis highlighted the roles of tissues outside the heart in heart failure risk. The results shed light on heart failure subtypes and could inform future treatments and preventive measures. Read more in Nature Genetics. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Endothelial cells (ECs) line the heart's blood vessels, but their involvement in atherosclerosis, LDL cholesterol levels, and coronary artery disease (CAD) hasn't been deeply studied. A team led by Nicholas Marston, MD, MPH and Rajat Gupta identified several EC-relevant genetic variants from among hundreds of CAD-associated loci, and built a new EC-centric polygenic risk score (PRS) for CAD. By analyzing data from UK Biobank and statin and PCSK9-blocker trials, they saw that their EC PRS captures an under-appreciated aspect of CAD risk and could help identify patients likely to respond to LDL cholesterol-lowering drugs. Learn more in Nature Medicine. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

The epithelial-to-mesenchymal transition (EMT) is a cancer phenomenon in which tumor cells reprogram themselves into a range of adaptable states, and is linked to poor outcomes. To better understand its underlying mechanisms, Fei Chen and his lab teamed up with Davide Cittaro (IRCCS San Raffaele Institute), MD Anderson's Luigi Perelli and Giannicola Genovese, and others to explore the EMT's role in pancreatic cancer. In Nature, they explain that the EMT drives genome instability and fuels the evolution of highly malignant and aggressive cells that end up dominating a tumor. They also theorize that targeting mesenchymal-like cells early might stop tumor progression. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Scientists in the Broad’s Spatial Technology Platform have developed a powerful new way to examine the role of genetic circuits in health and disease. Their method, Perturb-FISH, combines imaging-based spatial transcriptomic measurements with large-scale detection of CRISPR guide RNAs to reveal impacts of perturbations on gene expression and phenotype and uncover effects within and between cells. The researchers demonstrated Perturb-FISH’s potential to yield new cellular and functional insights, such as the effects of autism-related genes on cell activity and tumor-immune cell interactions in a xenograft model. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch #CRISPR

It’s well known that gene expression can vary within otherwise homogeneous cell types and impact development, aging, and cancer, but cell-to-cell variability in neurodevelopmental conditions has not been defined. Suraj Upadhya, Lindy Barrett, and others examined single-cell and single-nucleus RNA sequencing datasets derived from human brain-relevant cells and tissues and saw increased gene expression variability driven by trisomy 21 and CHD8 haploinsufficiency. Described in AJHG, their findings suggest that increased cell-to-cell variability may contribute to diverse phenotypes and provide a scaffold for understanding variability’s role in disease. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Plant glycosides (conjugates of secondary metabolites and carbohydrates) are abundant in fruits, vegetables, and nuts and are known to have positive effects on inflammatory disease, cancer, and neurodegenerative disorders. Whether and how the gut microbiome mediates these glycosides' impact is not well known. In Cell, Gavin Kuziel and Gabriel Lozano (Boston Children’s Hospital), Seth Rakoff-Nahoum, and colleagues report that certain members of the gut microbiome utilize these metabolites. They identified a system of enzymes within Bacteroides, the most common Gram-negative bacteria in the Western human gut, that processes different glycosides, helps resist colonization by the pathogen Clostridioides difficile, and maintains intestinal immune homeostasis. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch