CPRIT RP110532-C1

 

Title:

Texas Screening Alliance for Cancer Therapeutics

Description:

The Bioinformatics Core will actively communicate with investigators and screening programs to provide bioinformatics rational, optimize screening experimental design, satisfy the data analysis need, and provide advanced and transformative informatics support for effective target/drug discovery and deep interpretation of mechanism of action.

For the single and combinatorial target and drug screening projects (with a huge number of potential candidates), we could collect specific-aim related genomics data, involved targets and signaling pathways and perform systems biology analysis to prioritize specific aim related targets and drugs for screening, with clear bioinformatics rational support, to short the screening time and reduce the screening cost.

For the false positive issue, Bioinformatics Core will map the hit list to functional networks constructed by integrating rich genomics data, e.g. mRNA, miRNA, copy number aberration (CNA), loss of heterozygosity (LOH), protemomics data, e.g. MS and Reverse Phase Protein Arrays (RPPA), as well as sequence data with public interactions data to distinguish the true positives from false positives, and design secondary validation experiments.

To explore the Mechanisms of Action, Bioinformatics Core will integrate the interested screening results with genomics data to predict the involved signaling pathways using systems biology approaches. Based on the predicted mechanism of action, we have systems biology approaches to reposition existing drugs and their combinations on interested targets and disease (or cell lines).

To facilitate the bioinformatics analysis and information retrieval, we will build a database for the bio-registration, in which all the related drugs, shRNA/siRNA, genomics targets, screening results, as well as prior data will be associated together. Friendly user interfaces will be provided for information retrieval and visualization. To further speed up the bioinformatics analysis, the Pipeline Pilot software is used as a computational platform.

The Bioinformatics Core will prepare comprehensive bioinformatics reports to screening programs and investigators, which are significantly helpful for the better experimental design, the false positive hits reduction, the complex screening data interpretation, and the discovery of mechanisms of action.