CoTF-reg reveals cooperative transcription factors in oligodendrocyte gene regulation using single-cell multi-omics
Abstract Oligodendrocytes are the myelinating cells within the central nervous system, but the mechanisms by which transcription factors (TFs) cooperate for gene regulation in oligodendrocytes remain unclear. We introduce coTF-reg, an analytical framework that integrates scRNA-seq and scATAC-seq dat...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07570-6 |
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| _version_ | 1823861734243303424 |
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| author | Jerome J. Choi John Svaren Daifeng Wang |
| author_facet | Jerome J. Choi John Svaren Daifeng Wang |
| author_sort | Jerome J. Choi |
| collection | DOAJ |
| description | Abstract Oligodendrocytes are the myelinating cells within the central nervous system, but the mechanisms by which transcription factors (TFs) cooperate for gene regulation in oligodendrocytes remain unclear. We introduce coTF-reg, an analytical framework that integrates scRNA-seq and scATAC-seq data to identify cooperative TFs co-regulating the target gene (TG). First, we identify co-binding TF pairs in the same oligodendrocyte-specific regulatory regions. Next, we train a deep learning model to predict each TG expression using the co-binding TFs’ expressions. Shapley interaction scores reveal high interactions between co-binding TF pairs, such as SOX10-TCF12. Validation using oligodendrocyte eQTLs and their eGenes that are regulated by these cooperative TFs show potential regulatory roles for genetic variants. Experimental validation using ChIP-seq data confirms some cooperative TF pairs, such as SOX10-OLIG2. Prediction performance of our models is evaluated through holdout data and additional datasets, and an ablation study is also conducted. The results demonstrate stable and consistent performance. |
| format | Article |
| id | doaj-art-7e7573db14a948ad89a4d5984bc54a2c |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-7e7573db14a948ad89a4d5984bc54a2c2025-02-09T12:50:34ZengNature PortfolioCommunications Biology2399-36422025-02-018111310.1038/s42003-025-07570-6CoTF-reg reveals cooperative transcription factors in oligodendrocyte gene regulation using single-cell multi-omicsJerome J. Choi0John Svaren1Daifeng Wang2Waisman Center, University of Wisconsin-MadisonWaisman Center, University of Wisconsin-MadisonWaisman Center, University of Wisconsin-MadisonAbstract Oligodendrocytes are the myelinating cells within the central nervous system, but the mechanisms by which transcription factors (TFs) cooperate for gene regulation in oligodendrocytes remain unclear. We introduce coTF-reg, an analytical framework that integrates scRNA-seq and scATAC-seq data to identify cooperative TFs co-regulating the target gene (TG). First, we identify co-binding TF pairs in the same oligodendrocyte-specific regulatory regions. Next, we train a deep learning model to predict each TG expression using the co-binding TFs’ expressions. Shapley interaction scores reveal high interactions between co-binding TF pairs, such as SOX10-TCF12. Validation using oligodendrocyte eQTLs and their eGenes that are regulated by these cooperative TFs show potential regulatory roles for genetic variants. Experimental validation using ChIP-seq data confirms some cooperative TF pairs, such as SOX10-OLIG2. Prediction performance of our models is evaluated through holdout data and additional datasets, and an ablation study is also conducted. The results demonstrate stable and consistent performance.https://doi.org/10.1038/s42003-025-07570-6 |
| spellingShingle | Jerome J. Choi John Svaren Daifeng Wang CoTF-reg reveals cooperative transcription factors in oligodendrocyte gene regulation using single-cell multi-omics Communications Biology |
| title | CoTF-reg reveals cooperative transcription factors in oligodendrocyte gene regulation using single-cell multi-omics |
| title_full | CoTF-reg reveals cooperative transcription factors in oligodendrocyte gene regulation using single-cell multi-omics |
| title_fullStr | CoTF-reg reveals cooperative transcription factors in oligodendrocyte gene regulation using single-cell multi-omics |
| title_full_unstemmed | CoTF-reg reveals cooperative transcription factors in oligodendrocyte gene regulation using single-cell multi-omics |
| title_short | CoTF-reg reveals cooperative transcription factors in oligodendrocyte gene regulation using single-cell multi-omics |
| title_sort | cotf reg reveals cooperative transcription factors in oligodendrocyte gene regulation using single cell multi omics |
| url | https://doi.org/10.1038/s42003-025-07570-6 |
| work_keys_str_mv | AT jeromejchoi cotfregrevealscooperativetranscriptionfactorsinoligodendrocytegeneregulationusingsinglecellmultiomics AT johnsvaren cotfregrevealscooperativetranscriptionfactorsinoligodendrocytegeneregulationusingsinglecellmultiomics AT daifengwang cotfregrevealscooperativetranscriptionfactorsinoligodendrocytegeneregulationusingsinglecellmultiomics |