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Search for Master Regulators in Walking Cancer Pathways
Alexander E Kel1,2,3
1Institute of Chemical Biology and Fundamental Medicine, SBRAN, Novosibirsk, Russia. alexander.kel@genexplain.com.
Abstract:
In this chapter, we present an approach that allows a causal analysis of multiple "-omics" data with the help of an "upstream analysis" strategy. The goal of this approach is to identify master regulators in gene regulatory networks as potential drug targets for a pathological process. The data analysis strategy includes a state-of-the-art promoter analysis for potential transcription factor (TF)-binding sites using the TRANSFAC® database combined with an analysis of the upstream signal transduction pathways that control the activity of these TFs. When applied to genes that are associated with a switch to a pathological process, the approach identifies potential key molecules (master regulators) that may exert major control over and maintenance of transient stability of the pathological state. We demonstrate this approach on examples of analysis of multi-omics data sets that contain transcriptomics and epigenomics data in cancer. The results of this analysis helped us to better understand the molecular mechanisms of cancer development and cancer drug resistance. Such an approach promises to be very effective for rapid and accurate identification of cancer drug targets with true potential. The upstream analysis approach is implemented as an automatic workflow in the geneXplain platform ( www.genexplain.com ) using the open-source BioUML framework ( www.biouml.org ).
Insights
This study introduces an upstream analysis strategy to find master regulators in gene networks for identifying cancer drug targets. This method aids in understanding cancer development and drug resistance by analyzing multi-omics data.
Area of Science:
- Bioinformatics
- Systems Biology
- Genomics
Background:
- Identifying master regulators in gene regulatory networks is crucial for understanding pathological processes.
- Current methods often lack a comprehensive strategy for causal analysis of multi-omics data.
Purpose of the Study:
- To present an "upstream analysis" strategy for causal analysis of multi-omics data.
- To identify master regulators in gene regulatory networks as potential drug targets for pathological conditions, specifically cancer.
Main Methods:
- Utilizing a state-of-the-art promoter analysis with the TRANSFAC database for transcription factor (TF)-binding sites.
- Analyzing upstream signal transduction pathways controlling TF activity.
- Integrating transcriptomics and epigenomics data for multi-omics analysis.
Main Results:
- The approach successfully identified potential key molecules (master regulators) controlling pathological states.
- Demonstrated application on multi-omics cancer data revealed insights into cancer development and drug resistance mechanisms.
- Highlighted the potential for rapid and accurate identification of cancer drug targets.
Conclusions:
- The upstream analysis strategy offers a powerful approach for causal analysis of multi-omics data.
- This method facilitates the discovery of novel cancer drug targets by identifying master regulators.
- The approach enhances understanding of molecular mechanisms underlying cancer and drug resistance.
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