{"doi":"10.1101/2021.09.22.461437","title":"Nonparametric Interrogation of Transcriptional Regulation in Single-Cell RNA and Chromatin Accessibility Multiomic Data","abstract":"Abstract Epigenetic control of gene expression is highly cell-type- and context-specific. Yet, despite its complexity, gene regulatory logic can be broken down into modular components consisting of a transcription factor (TF) activating or repressing the expression of a target gene through its binding to a cis -regulatory region. Recent advances in joint profiling of transcription and chromatin accessibility with single-cell resolution offer unprecedented opportunities to interrogate such regulatory logic. Here, we propose a nonparametric approach, TRIPOD, to detect and characterize three-way relationships between a TF, its target gene, and the accessibility of the TF’s binding site, using single-cell RNA and ATAC multiomic data. We apply TRIPOD to interrogate cell-type-specific regulatory logic in peripheral blood mononuclear cells and contrast our results to detections from enhancer databases, cis -eQTL studies, ChIP-seq experiments, and TF knockdown/knockout studies. We then apply TRIPOD to mouse embryonic brain data during neurogenesis and gliogenesis and identified known and novel putative regulatory relationships, validated by ChIP-seq and PLAC-seq. Finally, we demonstrate TRIPOD on SHARE-seq data of differentiating mouse hair follicle cells and identify lineage-specific regulation supported by histone marks for gene activation and super-enhancer annotations.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":218182,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8631,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":815614,"name":"Yuriko Harigaya","orcid":"0000-0002-1879-5214","position":1,"is_corresponding":false},{"id":542962,"name":"Zhaojun Zhang","orcid":"0000-0003-0490-6507","position":2,"is_corresponding":false},{"id":421489,"name":"Hongpan Zhang","orcid":null,"position":3,"is_corresponding":false},{"id":43221,"name":"Chongzhi Zang","orcid":"0000-0003-4812-3627","position":4,"is_corresponding":false},{"id":17026,"name":"Nancy R. Zhang","orcid":"0000-0002-0880-5749","position":5,"is_corresponding":false},{"id":273462,"name":"Yuchao Jiang","orcid":"0000-0001-6905-6377","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:24.683898Z","pmid":null,"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":[]}