文献名：Integration and analysis of CPTAC proteomics data in the context of cancer genomics in the cBioPortal
Journal name: Molecular & Cellular Proteomics
Published: September 2019
IF：4.828
Author:
Pamela Wu1,2,3, Zachary J Heins4, James T Muller3, Lizabeth Katsnelson3, Ino de Bruijn4, Adam A Abeshouse4, Nikolaus Schultz4,5, David Fenyö1,2, Jianjiong Gao4,5
unit:
- New York University School of Medicine, Biochemistry and Pharmacology, New York 10016
- The system Institute of Genetics, School of Medicine, New York University, New York 10016
- , Sackler School of Medicine, New York University, New York 10016
- Memorial Sloan - Kettering Cancer Center, Marie-Josee and Henry R. Kravis Center for Molecular Oncology, New York 10065
- Memorial Sloan - Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York 10065
Species: human (Homo sapiens)
Technology: cBioPortal
I. Overview:
Proteomics Analysis of Clinical Oncology Alliance (Clinical Proteomic Tumor Analysis Consortium, CPTAC ) aims to analyze the application (or protein genomics) by large-scale proteomic and genomic promote understanding of the molecular basis of cancer. cBioPortal ( http://www.cbioportal.org/ ) is to conduct an excavation of the multi-dimensional genomic and clinical data cancer, visualization and analysis of open-source platform. We developed herein for the CPTAC members produced by mass spectrometry results to a data format compatible with the data pipeline cBioPortal data conversion process. CPTAC and 77 cases of breast cancer, 95 cases of colon cancer and integrated proteomic data 174 cases of ovarian cancer to cBioPortal in order to in the background of genomic and clinical data of the same tumor, a comprehensive analysis of proteomic data. In conjunction with mutation TCGA, copy number alterations, gene expression and DNA methylation information, CPTAC data after integration can be relatively easily analyzed under the excavation genomic and clinical information cBioPortal the background.
Second, the background:
Over the past decade, TCGA (The Cancer Genome Atlas) released more than thirty kinds of tumor genomic data, and by reverse-phase protein array platform (the Reverse Phase Protein Array, RPPA) outputs the proteome data to assess tumor nearly 150 abundance level of protein and 50 phosphorylated proteins. However RPPA technology combined with effectiveness and efficiency by post-translational modification of protein and antibody detection limits, can no longer meet current needs. Currently, CPTAC protein extends Genomics (Proteogenomic) technology has been included in the analysis in clear cell renal cell carcinoma, endometrial carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, glioblastoma, head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma and other types of cancer has been applied. By the same TCGA cancer patients have been analyzed analysis, CPTAC is associated with cancer genomics and proteomics data provides a new perspective, and proteomics linked to potential cancer phenotype. cBioPortal is an important resource for cancer genomics research, which includes all TCGA project data sets and multiple data sets collated from the literature, plus it has a user-friendly interface, visualization and integrated analysis capabilities, making cBioPortal become one of the cancer genomics researchers the most popular resources.
FIG. 1. cBioPortal functional interface description.
Third, the experimental design:
Figure 2. Example of Clinical Oncology integrated information, genomic and proteomic data
Fourth, the research results:
1. CPTAC the data using CDAP (Common Data Analysis Pipeline) to standardize the process, and then use MS-GF + for identification of the peptide segments.
The RefSeq ID matched to the corresponding protein gene, and quantified using a specific peptide.
3. post-translational modifications (mainly phosphorylation) was added to distinguish special tags: <HUGO gene symbol> _P {S, T, Y} <AA modified>. For example, 64 located on serine phosphorylation EIF4EBP1 expressed as EIF4EBP1_PS65. Meanwhile phosphorylated protein defined alias PHOSPHO <HUGO gene symbol> readily accessible.
4. Mass converted signal strength estimate of the number of copies of the protein per cell (optional):
N represents the number (Avogadro's number, 6.022 x 10 23 is the number of copies, and the measured protein), S mass spectrum signal values (measured and histone proteins), M representative of the quality of each cell DNA (estimated molar mass of 6.5 pg of protein and the measured values).
5. Support PTM and proteomic CDAP and classified documents from MaxQuant generated.
Currently cBioPortal have many applications: Web interface helps cancer patients to explore the regulation of mRNA and protein expression patterns of data; using the R package cgdsr explore cBioPortal data through its web API, to access a complete database now load mass spectral data; and load proteomics unpublished data or specific institution to a comprehensive analysis of the local private cBioPortal instance.
3. FIG clinical information 77 cases of breast cancer from TCGA, OncoPrint characteristic pattern group genomic and protein display.
Examples include clinical information mutational spectrum, age at diagnosis, overall survival, and details the type of cancer HER2 (ERBB2) IHC score, immunohistochemistry (immunohistochemistry) Rate for explaining whether immunohistochemical staining of tumor surface can be detected ERBB2 receptor: negative for 0-1 minutes, 2 minutes of resolving ambiguities, 3+ positive. Visualization wherein ERBB2 genomic and proteomic comprises mutations CPTAC based data, amplify the copy number, mRNA, protein phosphorylation and protein levels.
Fifth, the article highlights:
cBioPortal comprehensive information for interactive analysis provides a powerful help to meet the challenges of integrating multiple omics information of high-throughput sequencing and mass spectrometry technology brings. The integration of mass spectral data CPTAC to cBioPortal, increasing the accessibility of mass spectrometry based proteomics data in the context of genomics, and to each other between cancer researchers to explore and analyze cancer genomics and proteomics role provides an intuitive interface. Based on the current number of tumor samples from mass spectrometry analysis of the sample is still far less than the amount of reverse phase protein array analysis (Table 1), is expected to greatly increase in tumor mass spectrometry-based research in the future. The mass spectral data with genomic and clinical data integration, will reveal the cancer genome, a new association between proteomic and phenotypic provided the opportunity.
Cancer Research Table 1. cBioPortal used CPTAC mass spectrometry data, as of July 2019.
Note: Query Menu Location is when you set the parameters of the initial query tree structure of cancer research in the cBioPortal home page location.
Reading people: Xu Hongkai
Original link: https://www.mcponline.org/content/18/9/1893
DOI：https://doi.org/10.1074/mcp.TIR119.001673