Author : Hong Wang
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (129 download)
Book Synopsis Genome-scale Precision Proteomics Identifies Cancer Signaling Networks and Therapeutic Vulnerabilities by : Hong Wang
Download or read book Genome-scale Precision Proteomics Identifies Cancer Signaling Networks and Therapeutic Vulnerabilities written by Hong Wang and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Here we report that the ratio compression can be essentially resolved by the combination of pre-MS peptide fractionation, MS2-based interference detection and post-MS computational interference correction. To recapitulate the complexity of biological samples, we pooled tandem mass tag (TMT) labeled E. coli peptides at 1 : 3 : 10 ratios, and added in ~20-fold more rat peptides as background, followed by the analysis of two dimensional liquid chromatography-MS/MS. Systematic investigation indicated that the quantitative interference was impacted by LC fractionation depth, MS isolation window and peptide loading amount. Exhaustive fractionation (320 x 4 h) can nearly eliminate the interference and achieve results comparable to the MS3-based method. Importantly, the interference in MS2 scans can be estimated by the intensity of contaminated y1 product ions, and we thus developed an algorithm to correct reporter ion ratios of tryptic peptides. Our data indicated that intermediate fractionation (40 x 2 h) and y1 ion-based correction allowed accurate and deep TMT protein profiling, which represents a straightforward and affordable strategy in isobaric labeling proteomics High throughput omics approaches provide an unprecedented opportunity for dissecting molecular mechanisms in cancer biology. Here we present deep profiling of whole proteome, phosphoproteome and transcriptome in two high-grade glioma mouse models driven by mutated receptor tyrosine kinase (RTK) oncogenes, platelet-derived growth factor receptor alpha (PDGFRA) and neurotrophic receptor tyrosine kinase 1 (NTRK1), analyzing 13,860 proteins (11,941 genes) and 30,431 phosphosites by mass spectrometry.