d2ome, Software for in Vivo Protein Turnover Analysis Using Heavy Water Labeling and LC-MS, Reveals Alterations of Hepatic Proteome Dynamics in a Mouse Model of NAFLD
Creator
Sadygov R G; Avva J; Rahman M; Lee K; Ilchenko S; Kasumov T; Borzou A
Publisher
Journal of Proteome Research
Date
2018
2018-11
Description
Metabolic labeling with heavy water followed by LC-MS is a high throughput approach to study proteostasis in vivo. Advances in mass spectrometry and sample processing have allowed consistent detection of thousands of proteins at multiple time points. However, freely available automated bioinformatics tools to analyze and extract protein decay rate constants are lacking. Here, we describe d2ome-a robust, automated software solution for in vivo protein turnover analysis. d2ome is highly scalable, uses innovative approaches to nonlinear fitting, implements Grubbs' outlier detection and removal, uses weighted-averaging of replicates, applies a data dependent elution time windowing, and uses mass accuracy in peak detection. Here, we discuss the application of d2ome in a comparative study of protein turnover in the livers of normal vs Western diet-fed LDLR-/- mice (mouse model of nonalcoholic fatty liver disease), which contained 256 LC-MS experiments. The study revealed reduced stability of 40S ribosomal protein subunits in the Western diet-fed mice.
Subject
40S ribosomal proteins; algorithm; amino-acids; Biochemistry & Molecular Biology; dna; in vivo protein turnover; isotopomer; Mass spectrometry; metabolic labeling; NAFLD; nonlinear least-squares modeling; peak detection and integration; proliferation; protein half-life; proteome dynamics; proteostasis; quantification; rates; respiratory-chain; steatosis; UPR
d2ome, Software for in Vivo Protein Turnover Analysis Using Heavy Water Labeling and LC-MS, Reveals Alterations of Hepatic Proteome Dynamics in a Mouse Model of NAFLD.
Creator
Sadygov Rovshan G; Avva Jayant; Rahman Mahbubur; Lee Kwangwon; Ilchenko Sergei; Kasumov Takhar; Borzou Ahmad
Publisher
Journal of proteome research
Date
2018
2018-11
Description
Metabolic labeling with heavy water followed by LC-MS is a high throughput approach to study proteostasis in vivo. Advances in mass spectrometry and sample processing have allowed consistent detection of thousands of proteins at multiple time points. However, freely available automated bioinformatics tools to analyze and extract protein decay rate constants are lacking. Here, we describe d2ome-a robust, automated software solution for in vivo protein turnover analysis. d2ome is highly scalable, uses innovative approaches to nonlinear fitting, implements Grubbs' outlier detection and removal, uses weighted-averaging of replicates, applies a data dependent elution time windowing, and uses mass accuracy in peak detection. Here, we discuss the application of d2ome in a comparative study of protein turnover in the livers of normal vs Western diet-fed LDLR(-/-) mice (mouse model of nonalcoholic fatty liver disease), which contained 256 LC-MS experiments. The study revealed reduced stability of 40S ribosomal protein subunits in the Western diet-fed mice.
Subject
40S ribosomal proteins; in vivo protein turnover; isotopomer quantification; metabolic labeling; NAFLD; nonlinear least-squares modeling; peak detection and integration; protein half-life; proteome dynamics; UPR