Flexible modeling of regulatory networks improves transcription factor activity estimation
- PMID: 38806476
- PMCID: PMC11133322
- DOI: 10.1038/s41540-024-00386-w
Flexible modeling of regulatory networks improves transcription factor activity estimation
Abstract
Transcriptional regulation plays a crucial role in determining cell fate and disease, yet inferring the key regulators from gene expression data remains a significant challenge. Existing methods for estimating transcription factor (TF) activity often rely on static TF-gene interaction databases and cannot adapt to changes in regulatory mechanisms across different cell types and disease conditions. Here, we present a new algorithm - Transcriptional Inference using Gene Expression and Regulatory data (TIGER) - that overcomes these limitations by flexibly modeling activation and inhibition events, up-weighting essential edges, shrinking irrelevant edges towards zero through a sparse Bayesian prior, and simultaneously estimating both TF activity levels and changes in the underlying regulatory network. When applied to yeast and cancer TF knock-out datasets, TIGER outperforms comparable methods in terms of prediction accuracy. Moreover, our application of TIGER to tissue- and cell-type-specific RNA-seq data demonstrates its ability to uncover differences in regulatory mechanisms. Collectively, our findings highlight the utility of modeling context-specific regulation when inferring transcription factor activities.
© 2024. The Author(s).
Conflict of interest statement
The authors declare no competing interests.
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