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Welcome to the June 22, 2018 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the ӳ����ý and their collaborators.

Ducking the problem of network choice

Computational networks built from functional data types (e.g., epigenetic, proteomic) can reveal unsuspected relationships between genes. But differences in networks’ genetic coverage, connection patterns, and signal-to-noise ratios can make it hard to pick the best network for a given research question. To make it easier, Taibo Li, April Kim, and associate member Kasper Lage in the Stanley Center for Psychiatric Research and colleagues built , a platform for comparing networks’ attributes and running pathway analyses using the optimal approach. In this week's , they benchmarked GeNets’ underlying machine learning model, Quack, using genetic and functional data on psychiatric and neurodevelopmental disorders.

Scoping the genetics and biochemistry of benign kidney tumors

Renal oncocytomas (ROs) are benign, rare kidney tumors with large numbers of mitochondria. Raj Gopal, Sarah Calvo, ӳ����ý Metabolism Program co-director and institute member Vamsi Mootha, and collaborators ran genomic and metabolomic analyses of ROs to pinpoint their earliest genetic and biochemical changes. In , they show that mutations in the mitochondrial DNA for complex I (a cellular respiration enzyme) likely cause RO formation. They also found that RO cells adapt by boosting their production of glutathione (an antioxidant).

T cells' pep talk

Sets of immune cell proteins known as “co-inhibitory” receptors help ensure that the immune system works properly to control inflammation. However, in other cases, such as cancer, these receptors may lead to dysfunction of anti-tumor activity in immune cells. A team at the ӳ����ý, the Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women’s Hospital (BWH), and the Ann Romney Center for Neurologic Diseases at BWH performed RNA and protein expression profiling at single-cell resolution in mouse cells. Reporting in , associate member Vijay Kuchroo, core member and Klarman Cell Observatory and Cell Circuits Program director Aviv Regev, associate member Ana Anderson, Norio Chihara, and postdoctoral researcher Asaf Madi describe a module of co-inhibitory receptors – some already known and some new – and the molecular circuit that underlies their activity and regulates T cell function.

Re-thinking brain disorders

Reporting in , a new international consortium led by Verneri Anttila, Aiden Corvin (Trinity College Dublin), and institute member  in the Stanley Center for Psychiatric Research explored the genetic connections between 25 different psychiatric and neurological disorders, and 17 physical or cognitive measures, at a scale far eclipsing previous work. Chief among the findings: Psychiatric disorders share many genetic variants, while neurological disorders (such as Parkinson’s or Alzheimer’s) appear more distinct. The results indicate that psychiatric disorders likely have important similarities at a molecular level, which current diagnostics do not reflect. Learn more in a ӳ����ý news story and coverage in , STAT’s , and .

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