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Biomarker Analysis Tool
In collaboration with the bioinformatics firm 4HF Biotech GmbH which is a bioinformatics firm specializing in cancer data mining to discover new anti-cancer drugs, we offer data mining for analysis of the genetic signature of tumor cell lines that are sensitive for a customer drug to reveal potential biomarkers. The Biomarker Analysis is based on the sensitivity profile of the customer compound such as the results of the ProLiFiler - our Cell Line Panel Screening service. The Biomarker Analysis tool identifies genes or genetic alterations which are indicative for the efficacy of a drug and which may serve as predictive biomarkers in disease models and patient cohorts.
Primary data set: We will perform the ProLiFiler assay for testing the anti-proliferative effects of your drug on a set of 140 human tumor cell lines for IC50 determination. This is called the sensitivity profile of your compound.
Database: Our collaborator 4HF Biotech has built a comprehensive database, including data of more than 1,800 preclinical samples comprising multiple cancer datasets that are integrated into a single platform for visualization and statistical analysis. The data relevant for the Biomarker Analysis Tool are mutations (whole-exome sequencing), gene copy numbers, and gene expression data (Affymetrix).
Approach: The ProLiFiler results are correlated with the gene expression, mutation, and somatic copy number alteration data of the tumor cell lines that were used in the ProLiFiler study. A correlation analysis is performed for each cell line to determine the correlation of the drug sensitivity to each gene in regards to the expression level, mutation status, and/or somatic copy number.
Analysis: The Biomarker Analysis is performed with two statistical tests for each correlation; one uses the IC50 value of the test drug; the other compares the gene data of responding and non-responding cell lines.
Deliverables:
Mutation analysis
- Excel tables with raw data
- Graphical presentation of the correlation of mutation status for each gene and the drug sensitivity for each cell line
- Graphical presentation of the correlation of the position of each mutation and the drug sensitivity for each cell line
- Optional: Presentation of the amino acid position of relevant mutations
Gene copy analysis
- Excel tables with raw data
- Graphical presentation of the correlation of gene copy gain and the drug sensitivity for each cell line
- Graphical presentation of correlation of gene copy loss and the drug sensitivity for each cell line
- For selected genes, additional plots can be generated.
Gene expression analysis
- Excel table with raw data
- Graphical presentation of the correlation of the expression of each gene and drug sensitivity for every cell line
- Graphical presentation of the cluster analysis to identify differential gene expression signatures and different response rates to the test drug
- Optional: Literature search of gene function for most relevant genes
Additional analyses can be performed upon requests such as target gene analysis, pathway analysis, subtype analysis, hypothesis-driven analysis, predictive model development, and more.