Development of Novel Affinity Reagents: During the past fiscal year, the OSTP has continued to support an initiative for generating high affinity reagents to serve as tools for molecular interrogation of pathways that become altered during cancer development. Partnerships with two biotechnology companies, Beckton Dickinson Pharmingen and Rockland Immunochemicals have led to the creation of nearly 200 novel affinity reagents (polyclonal and monoclonal antibodies) against hundreds of key cancer-related targets of interest to CCR at no cost to the CCR investigators. These partnerships represent savings of over one million dollars to CCR and the NCI. The antibodies that have been developed through these partnerships includes: (1) novel candidate proteins for which no commercially available antibodies exist; (2) known proteins for which commercially available antibodies exist but fail to meet investigators' requirements; and (3) proteins with phosphorylation sites that may be of importance in pathways that are altered during cancer development. All of the antibody characterization data generated by participating CCR investigators is made available to the companies through a web site developed in collaboration between the OSTP and the Advanced Biomedical Computing Center (ABCC). The company uses the data in their marketing material when the antibodies are released for commercialization. Discovery of Novel Protein-Protein Interactions: The OSTP supported a number of programs for defining novel cancer relevant protein-protein interactions and cell signaling networks. For example, OSTP has been managing a major screening program to identify and characterize novel binding partners to a large number of cancer-related proteins currently under investigation within the CCR. A CCR-wide partnership with Myriad Genetics was developed to access their automated process for the large-scale identification of protein-protein interactions that is based on the Yeast Two-Hybrid (Y2H) methodology. This large-scale effort between CCR and Myriad has already generated a host of data (over 1,600 novel protein interactions have been transferred to CCR PI's to date) that are permitting the delineation of previously uncharacterized signaling pathways and a better understanding of the molecular basis underlying cancer. The data derived from these screens has been made available to CCR investigators through a web site developed in collaboration between OSTP and the ABCC. Facilitating Access to Genomic Technologies: The OSTP has been evaluating all commercially available platforms for microarray and other high throughput genomic technologies. To make the latest advances easily accessible to CCR researchers, the OSTP has established a number of contracts and pricing arrangements with companies providing genomic profiling technologies and services (Affymetrix, NimbleGen, Agilent, Illumina, GenUs, SuperArray, etc). These agreements have led to far lower cost and an efficient and easy way for CCR investigators to access these technologies. A subsidy program has been established providing 50% payment to the CCR community for all microarrays that are purchased from these companies or full-service microarray analysis that is requested. This funding mechanism has helped to extend the limited research dollars available to CCR laboratories and has permitted our researchers to conduct experiments that might otherwise be cost prohibitive. Many of the funded projects have led to important publications in top tier journals. Most recently, the OSTP has been coordinating CCRs efforts to access the ultra high throughput, next generation sequencing technologies. OSTP was involved in all aspects of acquisition of two Illumina/Solexa Genetic Analyzers that will be installed in two CCR laboratories. The OSTP will be providing investigators subsidy funds to make this very expensive technology accessible to many CCR labs. Tools for Bioinformatics and Biostatistics Analysis: In response to CCRs rapidly growing need to manage and analyze large sets of genomic and proteomic data, the OSTP has developed several partnerships with bioinformatics companies. At significant cost savings to NCI, OSTP negotiated a variety of license agreements on behalf of all NCI researchers for universal access to sophisticated tools for bioinformatic and statistical analysis of microarray experiments, arrayCGH studies, proteomic profiling studies, genomic analysis, and genetic screens. In addition, the OSTP has made a number of software applications for the investigation of pathways and biological association networks available to all of NCI. A CCR/NCI Integrated and Collaborative Knowledge Environment: To address the complexities associated with querying across the growing number and ever-expanding public and private databases, the OSTP has established a new program to develop a CCR/NCI integrated and collaborative knowledge environment in collaboration with Sophic Systems Alliance and Biomax. Software developed by Biomax enables the visualization of complex relationships between biological and biomedical data and information. It is designed to institutionalize knowledge by enabling the annotation of information stored in a central repository. The Knowledge Environment was configured to support research on different types of cancer, sources of data, and research strategies. The CCR/NCI laboratories are configuring the Biomax software according to their individual research requirements to determine its benefits to cancer research at CCR. The areas of research include ovarian cancer, metastasis, liver carcinogenesis, neuroblastoma, radiation oncology, and neuro-oncology. Each lab requires configuration of their software instance that is tailored to the type of research conducted in that lab. The Common CCR Knowledge Environment was configured to provide access to 35 public databases integrated into a single user interface, allowing scientists to query a wide range of data sources. Information derived through genomics, proteomics, pathway analysis, and clinical studies are combined into graphical representations of complex relationships. Future plans for the Common CCR Knowledge Environment include the integration of additional databases, genomic and proteomic analysis tools, and software
