vulcan

vulcan infers protein activity from gene expression and regulatory data to identify dysregulated oncoproteins and cofactors in cancer using enriched regulon analysis.

Key Features:

• VIPER algorithm: Employs Virtual Inference of Protein Activity by Enriched Regulon Analysis (VIPER) to assess protein activity from gene expression data.
• Integration with ChIP-Seq: Interrogates gene regulatory networks and analyzes differential binding signatures from ChIP-Seq data to identify cofactors significantly enriched in those signatures.
• Application to TCGA: Applies analyses across The Cancer Genome Atlas (TCGA) samples to evaluate the functional relevance of genetic alterations and to identify tumors with dysregulated activity of druggable oncoproteins even in the absence of detectable mutations.
• Predictive validation: Inferred protein activity predictions were validated by in vitro assays and outperformed traditional mutational analysis for predicting sensitivity to targeted inhibitors.

Scientific Applications:

• Cancer genomics: Evaluating the functional relevance of genetic alterations across TCGA samples.
• Oncoprotein and cofactor identification: Identifying tumors with dysregulated activity of druggable oncoproteins and enriched regulatory cofactors from expression and ChIP-Seq signatures.
• Therapeutic prediction: Predicting sensitivity to targeted inhibitors and prioritizing therapeutic targets based on inferred protein activity.

Methodology:

Uses the VIPER algorithm for enriched regulon analysis to infer protein activity from gene expression, interrogates gene regulatory networks, and analyzes differential binding signatures from ChIP-Seq data; applied to TCGA sample data.