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

iScience

2024

DOI: 10.1016/j.isci.2024.109124

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Predicting transcription factor activity using prior biological information

William M. Yashar,

Joseph Estabrook,

Hannah D. Holly

et al.

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2024

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References 70 publications

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Single-cell multi-omics analysis reveals cooperative transcription factors for gene regulation in oligodendrocytes

Choi,

Svaren,

Wang

2024

Preprint

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Oligodendrocytes are the myelinating cells within the central nervous system. Many oligodendrocyte genes have been associated with brain disorders. However, how transcription factors (TFs) cooperate for gene regulation in oligodendrocytes remains largely uncharacterized. To address this, we integrated scRNA-seq and scATAC-seq data to identify the cooperative TFs that co-regulate the target gene (TG) expression in oligodendrocytes. First, we identified co- binding TF pairs whose binding sites overlapped in oligodendrocyte-specific regulatory regions. Second, we trained a deep learning model to predict the expression level of each TG using the expression levels of co-binding TFs. Third, using the trained models, we computed the TF importance and TF-TF interaction scores for predicting TG expression by the Shapley interaction scores. We found that the co-binding TF pairs involving known important TF pairs for oligodendrocyte differentiation, such as SOX10-TCF12, SOX10-MYRF, and SOX10-OLIG2, exhibited significantly higher Shapley scores than others (t-test, p-value < 1e-4). Furthermore, we identified 153 oligodendrocyte-associated eQTLs that reside in oligodendrocyte-specific enhancers or promoters where their eGenes (TGs) are regulated by cooperative TFs, suggesting potential novel regulatory roles from genetic variants. We also experimentally validated some identified TF pairs such as SOX10-OLIG2 and SOX10-NKX2.2 by co-enrichment analysis, using ChIP-seq data from rat peripheral nerve.

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Single-cell multi-omics analysis reveals cooperative transcription factors for gene regulation in oligodendrocytes

Choi,

Svaren,

Wang

2024

Preprint

View full text Add to dashboard Cite

show abstract

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Predicting transcription factor activity using prior biological information

Cited by 1 publication

References 70 publications

Single-cell multi-omics analysis reveals cooperative transcription factors for gene regulation in oligodendrocytes

Single-cell multi-omics analysis reveals cooperative transcription factors for gene regulation in oligodendrocytes

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