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NCI Sheds Light on Two RFAs for Its Clinical Proteomics Initiative; SELDI, 2D Gels Snubbed

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In two requests for applications for its $104-million Clinical Proteomic Technologies Initiative for Cancer (see ProteoMonitor 7/8/2005), the National Cancer Institute seeks to "rigorously" assess current proteomic technology and develop new proteomic tools and computational methods.

"Hopefully, this will be the first step in building a foundation of technologies, data, reagents and standards, analysis systems, and infrastructure to systematically advance the understanding of protein biology in cancer," said Anna Barker, the deputy director of the NCI who spoke at a forum to present the RFAs this week in Bethesda, Md.

RFA No. 1

As part of its Clinical Proteomic Technology Assessment for Cancer RFA, which can be found here, the NCI seeks to develop standard protocols and clinical reference sets, and to evaluate methods to ensure data reproducibility.

According to Adam Clark, project manager at the National Institute of Health's Office of Technology and Industrial Relations, the main objectives of the CPTAC program are to evaluate performance of proteomic technology platforms and to standardize approaches to developing applications using these platforms; to evaluate proteomic platforms for their ability to analyze cancer-relevant proteomic changes in human clinical specimens; and to establish systematic ways to standardize proteomic protocols and data analysis among multiple laboratories.


"Hopefully, this will be the first step in building a foundation of technologies, data, reagents and standards, analysis systems, and infrastructure to systematically advance the understanding of protein biology in cancer."

In addition, the CPTAC program seeks to develop and implement uniform algorithms for sharing bioinformatics and proteomic data, as well as data mining tools; and to develop "well-defined" and "comprehensively characterized" sets of standard reference materials to serve as resources for the research community.

"Applicants must address each of these objectives in their application," said Clark, who spoke after Barker at the NCI forum.

Applications for the CPTAC RFA are due April 21. A letter of intent stating that an application will be submitted is due March 21.

Three to five research teams will be chosen for the CPTAC program. The program will be allotted $35.5 million over five years, with $8.5 million allotted for each of the first three years, and $5 million each for the fourth and fifth years.

To meet the second objective of analyzing cancer-relevant proteomic changes, each research team must have a minimum of 200 prospective samples from cancer patients, said Clark.

"You need to ensure that you have enough material to share amongst those in your participating team, as well as to store for future studies," said Clark.

Each CPTAC team will coordinate with the NCI's newly created Office of Biorepositories and Biospecimen Research to deal with issues with biospecimen practices that introduce variability into the studies. The office will also help researchers to deal with issues related to quality of specimens, and the ethical, legal, and regulatory limitations for specimen acquisition and use.

In addition to human studies, the NCI plans to have one common mouse model used by all CPTAC teams. The model will be provided by the NCI.

In terms of technologies to be used for the CPTAC program, 2D gel electrophoresis and SELDI are not acceptable for the program. According to Clark, these tools "will not be included in this program due to limitations in throughput, reproducibility, and peptide/protein identification."

Acceptable technologies for the program include MALDI mass spec, TOF mass spec, FTICR, tandem MS, and LC-MS.

Research teams must use at least two different mass spec platforms, said Clark. Also, at least one of the platforms must have at least two machines.

Each CPTAC research team will be overseen by a program coordination committee, which will consist of the principal investigators of the team, members of the NCI, and additional non-voting members added to ensure appropriate scientific expertise.

"You do have to acknowledge that the program coordination committee will have the ultimate say in experimental design," said Clark. "The PCC will ensure that appropriate inter-lab studies are properly designed and constructed, and will monitor activities."

RFA No. 2

The second RFA of the initiative, called the Advanced Proteomic Platforms and Computational Sciences RFA, is designed to support the development of innovative tools to do quantitative analysis of peptides and proteins of interest in clinical cancer studies, and to support the development of computational methods. The RFA can be found here.

"Current technology platforms have various performance endpoints that can be improved, including dynamic range, mass accuracy, sample throughput, peptide and protein identification, quantification, reproducibility, and cost," said Clark. "This RFA focuses on sample preparation and labeling technologies, sample fractionation technologies, mass spectrometry, protein capture and microarray technologies, and data analysis."

In addition, the RFA seeks "innovative" computational, statistical, and mathematical approaches for the analysis, processing, and "easy exchange" of large proteomic data sets.

The deadline for the RFA is April 11. A letter of intent stating that an application will be submitted is due March 11.

Ten research teams will be chosen for the Advanced Proteomic Platforms and Computational Sciences program. The program will be allotted $56 million over five years, with $10 million allotted the first year, $12 million the second year, $15 million the third year, $14 million the fourth year, and $5 million the fifth year.

As a third component of its Clinical Proteomic Technologies Initiative for Cancer, the NCI plans to develop a central public resource for well-characterized proteomic reagents and resources. The reagents and resources will include antibodies and affinity capture agents, standard reference materials, proteins, and peptides.

The NCI has allotted $12.5 million over five years for the proteomic reagents resources, with $2.5 million allotted each year.

For all three components of the initiative, teams will work with NCI's informatics platform, called the Cancer Biomedical Informatics Grid, or caBIG, to make data publicly available.

"Teams will be working with caBIG for data standardization and sharing of information," said Clark.

The NCI also plans to include in caBIG an interactive "catalog" of reagents and resources developed through the initiative.

-- Tien-Shun Lee ([email protected])

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