Novel brown adipose tissue candidate genes predicted by the human gene connectome Salazar Tortosa, Diego Francisco Ruiz Ruiz, Jonatan We would like to thank M. Thomas and R. de Casas for their helpful comments, and C. Osuna, F. Perfectti (CGL2013-47558-P), and the Scientific Supercomputing Center of the Universidad de Granada for sharing computational resources. We are also grateful to Ms. Carmen Sainz-Quinn for assistance with the English language. The study was supported by a Marie S. Curie Global Fellowship within the European Union research and innovation framework programme (2014-2020; ClimAHealth: 101030971). It was also supported by the Spanish Ministry of Economy and Competitiveness, Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01393), Fondos Estructurales de la Union Europea (FEDER), by the Fundacion Iberoamericana de Nutricion (FINUT), by the Redes tematicas de investigacion cooperativa RETIC (Red SAMID RD16/0022), by AstraZeneca HealthCare Foundation, by the University of Granada Plan Propio de Investigacion (Excellence actions: Unit of Excellence on Exercise and Health [UCEES]), and by the Junta de Andalucia, Consejeria de Economia, Conocimiento, Empresas y Universidad (ref. P18-624 RT-4455). Brown adipose tissue (BAT) is a promising therapeutic target against obesity. Therefore, research on the genetic architecture of BAT could be key for the development of successful therapies against this complex phenotype. Hypothesis-driven candidate gene association studies are useful for studying genetic determinants of complex traits, but they are dependent upon the previous knowledge to select candidate genes. Here, we predicted 107 novel-BAT candidate genes in silico using the uncoupling protein one (UCP1) as the hallmark of BAT activity. We first identified the top 1% of human genes predicted by the human gene connectome to be biologically closest to the UCP1, estimating 167 additional pathway genes (BAT connectome). We validated this prediction by showing that 60 genes already associated with BAT were included in the connectome and they were biologically closer to each other than expected by chance (p < 2.2 × 10− 16). The rest of genes (107) are potential candidates for BAT, being also closer to known BAT genes and more expressed in BAT biopsies than expected by chance (p < 2.2 × 10− 16; p = 4.39 × 10– 02). The resulting new list of predicted human BAT genes should be useful for the discovery of novel BAT genes and metabolic pathways. 2022-05-25T12:07:48Z 2022-05-25T12:07:48Z 2022-05-09 info:eu-repo/semantics/article Salazar-Tortosa, D.F... [et al.]. Novel brown adipose tissue candidate genes predicted by the human gene connectome. Sci Rep 12, 7614 (2022). [https://doi.org/10.1038/s41598-022-11317-2] http://hdl.handle.net/10481/74995 10.1038/s41598-022-11317-2 eng info:eu-repo/grantAgreement/EC/H2020/101030971 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España Nature