Due to a variety of experimental and computational issues, gene expression microarray data sets are far from optimally exploited. Limited sensitivity, wide spread and spurious cross hybridization and varying labeling efficiency are some of the well-known problems preventing the extraction of robust platform independent results from gene expression data. A careful combination of statistical and biochemical methods will be needed to produce reliable gene expression estimates. However, the current ingenious computational algorithms to analyze microarray data cannot be appropriately evaluated due to the lack of unbiased, realistic data sets, complete with raw data files and a large number of independent confirmations. We will establish exactly such a data base depositing our own data and actively collecting submissions from collaborators. We will demonstrate the utility of the proposed data base by determining the relative merit of several widely used microarray. normalization algorithms. We will also develop probe sequence based methods to reduce cross-hybridization noise in microarray measurements in order to enable the robust analysis of disease associated global gene expression profiles across different technologies and different data sources. The subset of reliable probes will be empirically verified then they will be distributed through Bioconductor. Microarray analysis is a powerful tool for improving disease classification, identifying novel therapeutic targets etc. The proposed data base along with the identification of reliable microarray probes will increase the reliability and potential utility of this promising technology. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Library of Medicine (NLM)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21LM008823-01A1
Application #
7088190
Study Section
Special Emphasis Panel (ZLM1-AP-R (J2))
Program Officer
Ye, Jane
Project Start
2006-04-15
Project End
2008-03-31
Budget Start
2006-04-15
Budget End
2007-03-31
Support Year
1
Fiscal Year
2006
Total Cost
$196,234
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Krzystanek, Marcin; Szallasi, Zoltan; Eklund, Aron C (2013) Biasogram: visualization of confounding technical bias in gene expression data. PLoS One 8:e61872
Lee, Alvin J X; Roylance, Rebecca; Sander, Jil et al. (2012) CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid-specific cancer cell death through autophagy induction. J Pathol 226:482-94
Li, Qiyuan; Birkbak, Nicolai J; Gyorffy, Balazs et al. (2011) Jetset: selecting the optimal microarray probe set to represent a gene. BMC Bioinformatics 12:474
Roylance, Rebecca; Endesfelder, David; Gorman, Patricia et al. (2011) Relationship of extreme chromosomal instability with long-term survival in a retrospective analysis of primary breast cancer. Cancer Epidemiol Biomarkers Prev 20:2183-94
Birkbak, Nicolai J; Eklund, Aron C; Li, Qiyuan et al. (2011) Paradoxical relationship between chromosomal instability and survival outcome in cancer. Cancer Res 71:3447-52
Endesfelder, David; McGranahan, Nicholas; Birkbak, Nicolai J et al. (2011) A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables. Oncotarget 2:529-37
Juul, Nicolai; Szallasi, Zoltan; Eklund, Aron C et al. (2010) Assessment of an RNA interference screen-derived mitotic and ceramide pathway metagene as a predictor of response to neoadjuvant paclitaxel for primary triple-negative breast cancer: a retrospective analysis of five clinical trials. Lancet Oncol 11:358-65
Li, Qiyuan; Eklund, Aron C; Juul, Nicolai et al. (2010) Minimising immunohistochemical false negative ER classification using a complementary 23 gene expression signature of ER status. PLoS One 5:e15031
Silver, Daniel P; Richardson, Andrea L; Eklund, Aron C et al. (2010) Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol 28:1145-53
Burrell, Rebecca A; Juul, Nicolai; Johnston, Stephen R et al. (2010) Targeting chromosomal instability and tumour heterogeneity in HER2-positive breast cancer. J Cell Biochem 111:782-90

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