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bioRxiv · 10.1101/2021.10.02.462873

An Information Theoretic Framework for Protein Activity Measurement

Griffin, A. T.·Vlahos, L. J.·Chiuzan, C.·Califano, A.
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Abstract

Nonparametric analytical Rank-based Enrichment Analysis (NaRnEA) is a novel gene set analysis method which leverages an analytical null model derived under the Principle of Maximum Entropy. NaRnEA critically improves over two widely used methods - Gene Set Enrichment Analysis (GSEA) and analytical Rank-based Enrichment Analysis (aREA) - as shown by differential activity measurement of ~2,500 transcriptional regulatory proteins across three cohorts in The Cancer Genome Atlas (TCGA) based on the enrichment of their transcriptional targets in differentially expressed genes. Phenotype-matched proteomic data from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) was used to evaluate measurement accuracy. We show that the sample-shuffling empirical null models leveraged by GSEA and aREA are overly conservative, a shortcoming that is critically addressed by NaRnEAs optimal analytical null model.

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Griffin, A. T., Vlahos, L. J., Chiuzan, C., Califano, A.. 2021-10-02. An Information Theoretic Framework for Protein Activity Measurement. https://doi.org/10.1101/2021.10.02.462873

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