{"doi":"10.1038/s42003-025-07570-6","title":"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 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.","journal":"Communications Biology","year":2025,"id":531048,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9475,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":329208,"name":"John Svaren","orcid":"0000-0003-2963-7921","position":1,"is_corresponding":false},{"id":249243,"name":"Daifeng Wang","orcid":"0000-0001-9190-3704","position":2,"is_corresponding":false},{"id":1036014,"name":"Jerome Choi","orcid":"0009-0008-7206-5758","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T02:51:10.077559Z","pmid":"39910206","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}