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Background: This paper describes the development of a web-based tool, GenDrux, which extracts and presents (over the Internet) information related to the disease-gene-drug nexus. This information is archived from the relevant biomedical literature using automated methods. GenDrux is designed to alleviate the difficulties of manually processing the vast biomedical literature to identify disease-gene-drug relationships. GenDrux will evolve with the literature without additional algorithmic modifications. Results: GenDrux, a pilot system, is developed in the domain of breast cancer and can be accessed at http://www. microarray.uab.edu/drug gene.pl. GenDrux can be queried based on drug, gene and/or disease name. From over 8,000 relevant abstracts from the biomedical literature related to breast cancer, we have archived a corpus of more than 4,000 articles that depict gene expression-drug activity relationships for breast cancer and related cancers. The archiving process has been automated. Conclusions: The successful development, implementation, and evaluation of this and similar systems when created may provide clinicians with a tool for literature management, clinical decision making, thus setting the platform for personalized therapy in the future. [ABSTRACT FROM AUTHOR]

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide. The recurrence rate ranges from 35-50% among early stage non-small cell lung cancer patients. To date, there is no fully-validated and clinically applied prognostic gene signature for personalized treatment. Methodology/Principal Findings: From genome-wide mRNA expression profiles generated on 256 lung adenocarcinoma patients, a 12-gene signature was identified using combinatorial gene selection methods, and a risk score algorithm was developed with Naïve Bayes. The 12-gene model generates significant patient stratification in the training cohort HLM & UM (n = 256; log-rank P = 6.96e-7) and two independent validation sets, MSK (n = 104; log-rank P = 9.88e-4) and DFCI (n = 82; logrank P = 2.57e-4), using Kaplan-Meier analyses. This gene signature also stratifies stage I and IB lung adenocarcinoma patients into two distinct survival groups (log-rank P<0.04). The 12-gene risk score is more significant (hazard ratio = 4.19, 95% CI: [2.08, 8.46]) than other commonly used clinical factors except tumor stage (III vs. I) in multivariate Cox analyses. The 12-gene model is more accurate than previously published lung cancer gene signatures on the same datasets. Furthermore, this signature accurately predicts chemoresistance/chemosensitivity to Cisplatin, Carboplatin, Paclitaxel, Etoposide, Erlotinib, and Gefitinib in NCI-60 cancer cell lines (P<0.017). The identified 12 genes exhibit curated interactions with major lung cancer signaling hallmarks in functional pathway analysis. The expression patterns of the signature genes have been confirmed in RT-PCR analyses of independent tumor samples. Conclusions/Significance: The results demonstrate the clinical utility of the identified gene signature in prognostic categorization. With this 12-gene risk score algorithm, early stage patients at high risk for tumor recurrence could be identified for adjuvant chemotherapy; whereas stage I and II patients at low risk could be spared the toxic side effects of chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]

Statistical methods have been intensively applied in genomic signal processing (Dougherty et al. 2005). For budding yeast Saccharomyces cerevisiae with around 6000 proteins, genome-wide protein-protein-interaction (PPI) (Fromont-Racine et al. 2000, Ito et al. 2001, Newman et al. 2000, and Uetz et al. 2000 among others) and protein subcellular localization (PSL) (Huh et al. 2003) data recently became available and for the latter the presence of 4152 proteins is experimentally tested in each of the 22 subcellular compartments. Recent work shows that multiple biological sources are helpful for both PSL and PPI predictions, and this paper studies statistical feasibility of modeling PPI from PSL since PSLs may play different marginal or joint roles in the complex regulatory network. However, our results indicate that PSL may be controversial for this purpose as an independent source. [ABSTRACT FROM AUTHOR]