The rapid worldwide rise in obesity rates over the past few decades imposes an urgent need to develop effective strategies for treating obesity and associated metabolic complications.Bariatric surgical pro-cedures,such as Roux-en-Y gastric bypass(RYGB)and vertical sleeve gastrectomy(VSG),currently provide the most effective treatment for obesity and type 2 diabetes(T2D),as well as for non-alcoholic steatohepatitis(NASH).However,the underlying mechanisms of the beneficial effects of bariatric surgery remain elusive.Recent studies have identified bile acids as potential signaling molecules involved in the beneficial effects of bariatric surgery.This review focuses on the most recent studies on the roles of bile acids and bile acid receptors Farnesoid X receptor(FXR)and G protein-coupled bile acid receptor 5(TGR5)in bariatric surgery.We also discuss the possibility of modulating bile acid signaling as a phar-macological therapeutic approach to treating obesity and its associated metabolic complications.

We aimed to develop a whole-genome sequencing(WGS)-based copy number variant(CNV)calling algorithm with the potential of replacing chromosomal microarray assay(CMA)for clinical diagnosis.JAX-CNV is thus developed for CNV detection from WGS data.The perfor-mance of this CNV calling algorithm was evaluated in a blinded manner on 31 samples and com-pared to the 112 CNVs reported by clinically validated CMAs for these 31 samples.The result showed that JAX-CNV recalled 100％of these CNVs.Besides,JAX-CNV identified an average of 30 CNVs per individual,representing an approximately seven-fold increase compared to calls of clinically validated CMAs.Experimental validation of 24 randomly selected CNVs showed one false positive,i.e.,a false discovery rate(FDR)of 4.17％.A robustness test on lower-coverage data revealed a 100％sensitivity for CNVs larger than 300 kb(the current threshold for College of American Pathologists)down to 10×coverage.For CNVs larger than 50 kb,sensi-tivities were 100％for coverages deeper than 20×,97％for 15×,and 95％for 10×.We developed a WGS-based CNV pipeline,including this newly developed CNV caller JAX-CNV,and found it capable of detecting CMA-reported CNVs at a sensitivity of 100％with about a FDR of 4％.We propose that JAX-CNV could be further examined in a multi-institutional study to justify the transition of first-tier genetic testing from CMAs to WGS.JAX-CNV is available at https://github.com/The J acksonLaboratory/JAX-CNV.