This proposal focuses on the development of statistical and computational methods for the analysis of data coming from high-throughput functional genomics technology such as microarrays. The research involves the extraction of meaningful relative expression levels from such experiments, and the subsequent identification of DNA sequence features such as promoters and transcription factor binding sites shared by genes identified from the arrays. This research involves the close collaboration of computational scientists and laboratory scientists. The projects involve studies of aging (in nematode, fruit fly and man), RNA structure prediction, identification of features of DNA replication in yeast, sensitivity to radiation therapy in human cancer patients, hybrid vigor in the development of oysters, and the evolution of E. coll. The common themes are the acquisition, analysis and interpretation of large amounts of data generated through the use of various microarray technologies. New approaches to research and training are needed for studying problems in genomics and molecular biology. The traditional one-person or student-advisor study is unlikely to be successful. Instead a multidisciplinary approach must be devised, with mathematical scientists involved with experimentalists to understand the motivations for the experiments and the limitations of the studies. Post-doctoral and graduate students from mathematics and statistics must learn the skills of cross-disciplinary communication and collaboration. This research program is specifically structured to provide practical and continuing training in this process.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM067243-04
Application #
6906407
Study Section
Special Emphasis Panel (ZGM1-CMB-0 (MB))
Program Officer
Eckstrand, Irene A
Project Start
2002-07-15
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2007-06-30
Support Year
4
Fiscal Year
2005
Total Cost
$406,250
Indirect Cost
Name
University of Southern California
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Jiang, Rong; Tavare, Simon; Marjoram, Paul (2009) Population genetic inference from resequencing data. Genetics 181:187-97
Waskar, Morris; Landis, Gary N; Shen, Jie et al. (2009) Drosophila melanogaster p53 has developmental stage-specific and sex-specific effects on adult life span indicative of sexual antagonistic pleiotropy. Aging (Albany NY) 1:903-36
Szyjka, Shawn J; Aparicio, Jennifer G; Viggiani, Christopher J et al. (2008) Rad53 regulates replication fork restart after DNA damage in Saccharomyces cerevisiae. Genes Dev 22:1906-20
Grover, Dhruv; Tower, John; Tavare, Simon (2008) O fly, where art thou? J R Soc Interface 5:1181-91
Curtis, Christina; Landis, Gary N; Folk, Donna et al. (2007) Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes. Genome Biol 8:R262
Skvortsov, Dmitriy; Abdueva, Diana; Stitzer, Michael E et al. (2007) Using expression arrays for copy number detection: an example from E. coli. BMC Bioinformatics 8:203
Skvortsov, Dmitriy; Abdueva, Diana; Curtis, Christina et al. (2007) Explaining differences in saturation levels for Affymetrix GeneChip arrays. Nucleic Acids Res 35:4154-63
Xu, Weihong; Aparicio, Jennifer G; Aparicio, Oscar M et al. (2006) Genome-wide mapping of ORC and Mcm2p binding sites on tiling arrays and identification of essential ARS consensus sequences in S. cerevisiae. BMC Genomics 7:276
Jiang, Rong; Marjoram, Paul; Borevitz, Justin O et al. (2006) Inferring population parameters from single-feature polymorphism data. Genetics 173:2257-67
Abdueva, Diana; Skvortsov, Dmitriy; Tavare, Simon (2006) Non-linear analysis of GeneChip arrays. Nucleic Acids Res 34:e105

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