Sufficient general clinical knowledge, DNA sequence technology and understanding of genetic mutations for over 2,600 human genes can support beginning the integration of individual genome sequence into clinical practice for a number of medical specialties. With the 2007 deployment of novel DNA sequence technologies that permit cost-effective interrogation of individual genome sequence for the subset of the genome of clinical interest, the potential for rapid impact on patient care is palpable. However, the lack of a suitable human genome analysis and interpretation platform is a substantial barrier that will slow implementation as these new sequence technologies are adopted. To address this gap, we plan to create a commercial software platform supporting the input, analysis, storage and reporting of individual human genome sequence providing a genetic health assessment for nucleotide sequence attributes that may be either assets or liabilities depending on clinical context. This sixteen- month SBIR Phase I proposal will support the development of a software prototype capable of supporting collaboration studies and will compile the information necessary for our first pilot study, individual genome analysis for the Hemostasis and Thrombosis clinical area selected based on its suitability for early studies in human systems biology that would potentially have rapid clinical utility. The challenges to be addressed in the phase I effort are first to develop applications capable of highly accurate, automated identification, extraction and ordered storage of individual human variation data followed by the testing of these variations against a knowledgebase of previously characterized human mutations and variations associated with heritable diseases. Additional challenges will be to structure phenotypic and mutation information into formats useful to researchers and clinicians. Successful completion of the phase I effort will result in comprehensive identification of DNA sequence variation from individual genome sequence data and the determination of performance metrics that will be feasible to scale in phase II for the commercial software platform development capable of processing a target minimum of 100 individual genomes per day. The impact of this work will be to initially facilitate human systems biology studies that will demonstrate how such results can be utilized for diagnosis, prognosis and development of personalized therapeutic plans and ultimately, support diagnostic procedures. The software prototype and the first release of the commercial grade software will make key contributions to bringing personalized medicine to the bedside in the next five years.

Public Health Relevance

Our knowledge of genetic contributions to disease and health is multifaceted and forms a broad spectrum; however, to apply this knowledge directly to improve health and impact patient care, the means to produce individual human genome sequence data, analyze the data and formulate the results into meaningful reports requires complex software and information systems which do not yet exist. The software and information technologies we propose to develop will contribute to the understanding of individual genetic variation and it application for diagnostics, determining disease prognosis and for selecting individualized treatment programs. Potential application of computationally structured knowledge and individual genome data can be applied across every therapeutic area and branch of medicine; this work complements the Biomedical Information Science and Technology Initiative (BISTI) and strongly supports the National Institutes of Health RoadMap objectives. ? ? ? ?

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZRG1-BST-D (10))
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Bonazzi, Vivien
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3rd Millennium, Inc
United States
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Fechtel, Kim; Osterbur, Marika L; Kehrer-Sawatzki, Hildegard et al. (2011) Delineating the Hemostaseome as an aid to individualize the analysis of the hereditary basis of thrombotic and bleeding disorders. Hum Genet 130:149-66