scholarly journals Faculty Opinions recommendation of High-throughput mediation analysis of human proteome and metabolome identifies mediators of post-bariatric surgical diabetes control.

Author(s):  
Om P Ganda
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jonathan M. Dreyfuss ◽  
Yixing Yuchi ◽  
Xuehong Dong ◽  
Vissarion Efthymiou ◽  
Hui Pan ◽  
...  

AbstractTo improve the power of mediation in high-throughput studies, here we introduce High-throughput mediation analysis (Hitman), which accounts for direction of mediation and applies empirical Bayesian linear modeling. We apply Hitman in a retrospective, exploratory analysis of the SLIMM-T2D clinical trial in which participants with type 2 diabetes were randomized to Roux-en-Y gastric bypass (RYGB) or nonsurgical diabetes/weight management, and fasting plasma proteome and metabolome were assayed up to 3 years. RYGB caused greater improvement in HbA1c, which was mediated by growth hormone receptor (GHR). GHR’s mediation is more significant than clinical mediators, including BMI. GHR decreases at 3 months postoperatively alongside increased insulin-like growth factor binding proteins IGFBP1/BP2; plasma GH increased at 1 year. Experimental validation indicates (1) hepatic GHR expression decreases in post-bariatric rats; (2) GHR knockdown in primary hepatocytes decreases gluconeogenic gene expression and glucose production. Thus, RYGB may induce resistance to diabetogenic effects of GH signaling.Trial Registration: Clinicaltrials.gov NCT01073020.


Author(s):  
Joanna S. Albala ◽  
Ken Franke ◽  
Ian R. McConnell ◽  
Karen L. Pak ◽  
Peg A. Folta ◽  
...  

2018 ◽  
Vol 16 (01) ◽  
pp. 1740011 ◽  
Author(s):  
Olga Kiseleva ◽  
Ekaterina Poverennaya ◽  
Alexander Shargunov ◽  
Andrey Lisitsa

Proteomic challenges, stirred up by the advent of high-throughput technologies, produce large amount of MS data. Nowadays, the routine manual search does not satisfy the “speed” of modern science any longer. In our work, the necessity of single-thread analysis of bulky data emerged during interpretation of HepG2 proteome profiling results for proteoforms searching. We compared the contribution of each of the eight search engines (X!Tandem, MS-GF[Formula: see text], MS Amanda, MyriMatch, Comet, Tide, Andromeda, and OMSSA) integrated in an open-source graphical user interface SearchGUI ( http://searchgui.googlecode.com ) into total result of proteoforms identification and optimized set of engines working simultaneously. We also compared the results of our search combination with Mascot results using protein kit UPS2, containing 48 human proteins. We selected combination of X!Tandem, MS-GF[Formula: see text] and OMMSA as the most time-efficient and productive combination of search. We added homemade java-script to automatize pipeline from file picking to report generation. These settings resulted in rise of the efficiency of our customized pipeline unobtainable by manual scouting: the analysis of 192 files searched against human proteome (42153 entries) downloaded from UniProt took 11[Formula: see text]h.


Molecules ◽  
2018 ◽  
Vol 23 (6) ◽  
pp. 1448 ◽  
Author(s):  
Jian Zhang ◽  
Haiting Chai ◽  
Song Guo ◽  
Huaping Guo ◽  
Yanling Li

PROTEOMICS ◽  
2005 ◽  
Vol 5 (17) ◽  
pp. 4327-4337 ◽  
Author(s):  
Peter Nilsson ◽  
Linda Paavilainen ◽  
Karin Larsson ◽  
Jenny Ödling ◽  
Mårten Sundberg ◽  
...  

2019 ◽  
Author(s):  
Jonathan M Dreyfuss ◽  
Yixing Yuchi ◽  
Hui Pan ◽  
Xuehong Dong ◽  
Donald C. Simonson ◽  
...  

AbstractMolecular mechanisms by which Roux-en-Y gastric bypass (RYGB) improves glycemic control and metabolism in type 2 diabetes (T2D) remain incompletely understood. In the SLIMM-T2D trial, participants with T2D were randomized to RYGB or nonsurgical management and their fasting plasma proteome and metabolome were analyzed for up to 3 years. To identify analytes that mediate improvement in outcomes, we developed a high-throughput mediation analysis method (Hitman), which is significantly more powerful than existing methods. Top-ranking analyte mediators of glycemia improvement were growth hormone receptor and prolylhydroxyproline, which were more significant than any clinical mediator, including BMI. Beta-alanine and Histidine Metabolism (both including CNDP1) were top differentially regulated pathways, and Valine, Leucine and Isoleucine Degradation was also a top differentially-regulated pathway and a top mediator of improvement in insulin resistance. The identified analytes may serve as novel targets for T2D therapy. More broadly, Hitman can identify analyte mediators of outcomes in randomized trials for which high-throughput data are available.


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