Predicting transcription factor activity using prior biological information

Yashar, William M.; Estabrook, Joseph; Holly, Hannah D.; Somers, Julia; Nikolova, Olga; Babur, Özgün; Braun, Theodore P.; Demir, Emek

doi:10.1016/j.isci.2024.109124

Title: Predicting transcription factor activity using prior biological information

Journal Article · 05 February 2024 · iScience

DOI: https://doi.org/10.1016/j.isci.2024.109124 · OSTI ID:2471615

^[1]; Estabrook, Joseph ^[1]; Holly, Hannah D. ^[1]; Somers, Julia ^[1]; Nikolova, Olga ^[1]; Babur, Özgün ^[2]; Braun, Theodore P. ^[1];

^[3]

Oregon Health & Science University, Portland, OR (United States)
University of Massachusetts, Boston, MA (United States)
Oregon Health & Science University, Portland, OR (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Dysregulation of normal transcription factor activity is a common driver of disease. Therefore, the detection of aberrant transcription factor activity is important to understand disease pathogenesis. We have developed Priori, a method to predict transcription factor activity from RNA sequencing data. Priori has two key advantages over existing methods. First, Priori utilizes literature-supported regulatory information to identify transcription factor-target gene relationships. It then applies linear models to determine the impact of transcription factor regulation on the expression of its target genes. Second, results from a third-party benchmarking pipeline reveals that Priori detects aberrant activity from 124 single-gene perturbation experiments with higher sensitivity and specificity than 11 other methods. We applied Priori and other top-performing methods to predict transcription factor activity from two large primary patient datasets. Our work demonstrates that Priori uniquely discovered significant determinants of survival in breast cancer and identified mediators of drug response in leukemia.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2471615

Journal Information:: iScience, Journal Name: iScience Journal Issue: 3 Vol. 27; ISSN 2589-0042

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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