Clinical Proteomic Technologies for Cancer Initiative 2006-2011
The Clinical Proteomic Technologies for Cancer Initiative, launched in 2006, was developed to address the pre-analytical and analytical variability issues that are major barriers to the field of proteomics. These barriers were: (1) experimental design; (2) technological and technical aspects of protein identification; (3) variability related to biospecimens collection; (4) the processes of data acquisition, analysis, and reporting; (5) the lack of reproducible proteomic technologies; and (6) the lack of highly characterized and standardized reagents. The initiative was composed of three integrated programs that worked together to overcome these barriers:
- Clinical Proteomic Technology Assessment for Cancer network: Network of 5 multidisciplinary teams that collaborated on research projects to increase the understanding of experimental and analytical sources of error for existing technologies.
- Advanced Proteomic Platforms and Computational Sciences: Individual investigators that developed new analytical tools, technology, and software to improve the accuracy and reproducibility of proteomic measurement.
- Proteomic Reagents and Resources component: The component provided high quality, well-characterized reagents (antibodies), data, and standard reference materials for the research community.
Key Research Outputs
The program has showed the effectiveness of a multidisciplinary team approach to address the issues of variability in proteomic technologies. A key outcome of the program was the improvement of the proteomic biomarker development pipeline. Prior to the initiative, development of biomarkers typically relied on a discovery process followed by clinical validation (qualification) stage, where hundreds to thousands of biomarker candidates are detected but only a few are transitioned to full clinical qualification studies due to the prohibitive expense and time of large-scale validation studies for each candidate. Initiative Investigators developed a preclinical 2-stage workflow designed to streamline the transition of proteins from initial discovery/identification toward large-scale clinical qualification studies. This workflow entails a Discovery Unit (stage 1) where a tumor is comprehensively interrogated for protein content, followed by a Verification Unit (stage 2) where prioritized proteins are then measured for their presence in blood and other bodily fluids if warranted. More information about the redeveloped biomarker development pipeline utilizing multiple reaction monitoring mass spectrometry is available here. More information related to the reconstructed biomarker pipeline and other key research outputs are available in the 2009 CPTC Annual Report, to download click here.
Additional outputs from the initiative include:
- Reference Materials: In collaboration with the National Institute of Standards and Technology, a soluble yeast protein extract reference material and software metrics tool (to monitor the performance of liquid chromatography-mass spectrometry systems) were developed. This, along with its publicly available reference datasets, provides a foundation for laboratories to benchmark their own performance, improve upon current methods, and evaluate new for technologies.
- Software Tools: Skyline, a multiple-reaction monitoring mass spectrometry analytical tool was developed and tested through the initiative. This open source and freely available software tool can be used on a host of mass spectrometric platforms in both commercial and academic settings. More information and downloads are available here.
- Data Sharing: The Amsterdam Principles were developed in coordination with the global proteomics community; these principles serves as a starting point for bringing proteomics data release practices in line with those of the genomics community in order to maximize benefits to society. To read these principles click here.
- Improved quality control of biospecimens for proteomic experiments: The CPTAC network developed standard operating procedures for collection, processing and storage of plasma; established a blood (plasma) repository; and developed a multisite biorepository with distribution procedures. These standard procedures remove a great deal of bias in the collection of patient samples.
- Community accessible resources: Well-characterized antibody reagents with data from standardized processes were made publicly available to the research community online at http://antibodies.cancer.gov.
- Regulatory Science: Initiative Investigators developed public mock 510(k) presubmission documents that were published with the comments from the Food and Drug Administration review staff. These first-of-their-kind public documents benefit the global proteomics community in designing appropriate studies that support analytical and clinical claims, streamlines the regulatory process by providing examples of submission formatting, and provides a framework for the future creation of similar open-access documents. For access to these documents, click here.