Measuring cancer biomarker candidates by targeted ms and ab enrichment

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Project Title: Measuring cancer biomarker candidates by targeted ms and ab enrichment
Project Number: 1U24CA126476-01
Project web address: Follow on NIH
 
Project Description:
We propose to assess the robustness of a high-throughput mass spectrometric (MS) technology platform for quantitative measurement of multiple candidate biomarker proteins in complex samples such as human plasma. Specific assays will be developed for 300 candidate biomarker proteins drawn from published literature, pathway analysis, microarray, and proteomics discovery efforts. These assays will be used to measure biomarker levels in 200 selected cancer and 200 control plasma samples at three different laboratory sites using two variant MS platforms. The results will characterize the quantitative reproducibility of the assay methodology within- and between-laboratories and over time. A series of standardized reagents will be developed allowing the assays to be implemented in other laboratories using similar standardized instrumentation. Our measurement platform makes use of well-established quantitative MS techniques used in the routine measurement of small molecules: so-called "multiple reaction monitoring" (or MRM) assays and stable isotope labeled internal standards for quantitation, here in the form of synthetic, labeled peptides. By measuring both the labeled and unlabeled (sample-derived) peptides by MS, the method provides a quantitative measure of the relative amounts of the signature peptide and therefore the protein that it is derived from. In order to access lower abundance biomarkers (those in the lower 5 orders of magnitude of the overall 10 orders of magnitude plasma abundance scale) we will employ specific enrichment techniques using immobilized anti-peptide antibodies. After extensive optimization and characterization, our assays will be deployed on clinical plasma samples from breast cancer cases and controls. Key outcomes of this project will be to demonstrate 1) that we can make sensitive and specific assays quickly and inexpensively; 2) that the assays can be highly multiplexed, greatly reducing the cost-per-analyte; and 3) that the protocols and technology can be standardized and distributed. Several members of our CPTAC team are currently involved in proteomic consortia aimed at MS-based discovery of candidate breast cancer biomarkers in human samples and mouse models. These efforts are generating robust datasets that will also be leveraged by this CPTAC team to inform selection of candidates for assay development and ultimate validation.
 
Project Terms:
neoplasm /cancer
Project Title: Measuring cancer biomarker candidates by targeted ms and ab enrichment
Project Number: 1U24CA126476-01
Project web address: Follow on NIH
Organization: Massachusetts Institute Of Technology, United States, Massachusetts, CAMBRIDGE
Principal Investigators (PI): Carr Steven A, US
 
Project Categories:
Natural Sciences > Aging-related markers and targets > Biomarkers of diseases > Cancer biomarkers
 
Other Information:
Fiscal Year: 2006
Project Start Date: 28 September 2006
Project End Date: 31 August 2011
Project program: Resource-Related Research Projects--Cooperative Agreements
 
Project Funding Information:
Funding Mechanism: Cooperative agreements
Year Funding Organization Total Funding, $
2006 NIH - National Cancer Institute $2,904,304
Project Title: Measuring cancer biomarker candidates by targeted ms and ab enrichment
Project Number: 1U24CA126476-01
Project web address: Follow on NIH
 
Title FY Funding
There are no results for this project in database.
Project Title: Measuring cancer biomarker candidates by targeted ms and ab enrichment
Project Number: 1U24CA126476-01
Project web address: Follow on NIH
 
Title Journal Year Country Rel
Large-Scale Interlaboratory Study to Develop, Analytically Validate and Apply Highly Multiplexed, Quantitative Peptide Assays to Measure Cancer-Relevant Proteins in Plasma. Mol Cell Proteomics 2015 united states
Calibration using constrained smoothing with applications to mass spectrometry data. Biometrics 2014 united states
Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS). Mol Cell Proteomics 2013 united states
Sequential multiplexed analyte quantification using peptide immunoaffinity enrichment coupled to mass spectrometry. Mol Cell Proteomics 2012 united states
Multiplexed quantification of estrogen receptor and HER2/Neu in tissue and cell lysates by peptide immunoaffinity enrichment mass spectrometry. Proteomics 2012 germany
Shotgun protein sequencing with meta-contig assembly. Mol Cell Proteomics 2012 united states
Statistical characterization of multiple-reaction monitoring mass spectrometry (MRM-MS) assays for quantitative proteomics. BMC Bioinformatics 2012 england
Precision of heavy-light peptide ratios measured by maldi-tof mass spectrometry. J Proteome Res 2012 united states
Interlaboratory evaluation of automated, multiplexed peptide immunoaffinity enrichment coupled to multiple reaction monitoring mass spectrometry for quantifying proteins in plasma. Mol Cell Proteomics 2012 united states
Modification site localization scoring: strategies and performance. Mol Cell Proteomics 2012 united states
Quantification of proteins using peptide immunoaffinity enrichment coupled with mass spectrometry. J Vis Exp 2011 united states
A face in the crowd: recognizing peptides through database search. Mol Cell Proteomics 2011 united states
MALDI immunoscreening (MiSCREEN): a method for selection of anti-peptide monoclonal antibodies for use in immunoproteomics. J Immunol Methods 2011 netherlands
A pipeline that integrates the discovery and verification of plasma protein biomarkers reveals candidate markers for cardiovascular disease. Nat Biotechnol 2011 united states
A targeted proteomics-based pipeline for verification of biomarkers in plasma. Nat Biotechnol 2011 united states
Peptide immunoaffinity enrichment coupled with mass spectrometry for peptide and protein quantification. Clin Lab Med 2011 united states
Evaluation of large scale quantitative proteomic assay development using peptide affinity-based mass spectrometry. Mol Cell Proteomics 2011 united states
Automated detection of inaccurate and imprecise transitions in peptide quantification by multiple reaction monitoring mass spectrometry. Clin Chem 2010 united states
Optimizing performance of glycopeptide capture for plasma proteomics. J Proteome Res 2010 united states
Integration of proteomic-based tools for improved biomarkers of myocardial injury. Clin Chem 2010 united states
Introduction: Advances in protein analysis for the clinical laboratory. Clin Chem 2010 united states
The clinical plasma proteome: a survey of clinical assays for proteins in plasma and serum. Clin Chem 2010 united states
Effect of collision energy optimization on the measurement of peptides by selected reaction monitoring (SRM) mass spectrometry. Anal Chem 2010 united states
Repeatability and reproducibility in proteomic identifications by liquid chromatography-tandem mass spectrometry. J Proteome Res 2010 united states
A quantitative study of the effects of chaotropic agents, surfactants, and solvents on the digestion efficiency of human plasma proteins by trypsin. J Proteome Res 2010 united states
Assay development for the determination of phosphorylation stoichiometry using multiple reaction monitoring methods with and without phosphatase treatment: application to breast cancer signaling pathways. Anal Chem 2010 united states
Mass-spectrometry-based clinical proteomics--a review and prospective. Analyst 2010 england
Automated screening of monoclonal antibodies for SISCAPA assays using a magnetic bead processor and liquid chromatography-selected reaction monitoring-mass spectrometry. J Immunol Methods 2010 netherlands
An automated and multiplexed method for high throughput peptide immunoaffinity enrichment and multiple reaction monitoring mass spectrometry-based quantification of protein biomarkers. Mol Cell Proteomics 2010 united states
Performance metrics for liquid chromatography-tandem mass spectrometry systems in proteomics analyses. Mol Cell Proteomics 2010 united states
Interlaboratory study characterizing a yeast performance standard for benchmarking LC-MS platform performance. Mol Cell Proteomics 2010 united states
Quantification of cardiovascular biomarkers in patient plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics 2009 united states
SISCAPA peptide enrichment on magnetic beads using an in-line bead trap device. Mol Cell Proteomics 2009 united states
Anti-peptide antibody screening: selection of high affinity monoclonal reagents by a refined surface plasmon resonance technique. J Immunol Methods 2009 netherlands
Prediction of high-responding peptides for targeted protein assays by mass spectrometry. Nat Biotechnol 2009 united states
Developing multiplexed assays for troponin I and interleukin-33 in plasma by peptide immunoaffinity enrichment and targeted mass spectrometry. Clin Chem 2009 united states
Directed sample interrogation utilizing an accurate mass exclusion-based data-dependent acquisition strategy (AMEx). J Proteome Res 2009 united states
Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma. Nat Biotechnol 2009 united states
The evolving role of mass spectrometry in cancer biomarker discovery. Cancer Biol Ther 2009 united states
A human proteome detection and quantitation project. Mol Cell Proteomics 2009 united states
The interface between biomarker discovery and clinical validation: The tar pit of the protein biomarker pipeline. Proteomics Clin Appl 2008
Protein quantitation through targeted mass spectrometry: the way out of biomarker purgatory? Clin Chem 2008 united states
Accurate inclusion mass screening: a bridge from unbiased discovery to targeted assay development for biomarker verification. Mol Cell Proteomics 2008 united states
High-abundance polypeptides of the human plasma proteome comprising the top 4 logs of polypeptide abundance. Clin Chem 2008 united states
Quantitative, multiplexed assays for low abundance proteins in plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics 2007 united states
Project Title: Measuring cancer biomarker candidates by targeted ms and ab enrichment
Project Number: 1U24CA126476-01
Project web address: Follow on NIH
 
Title Year
Project Title: Measuring cancer biomarker candidates by targeted ms and ab enrichment
Project Number: 1U24CA126476-01
Project web address: Follow on NIH
 
Title Phase Year