{"doi":"10.1101/2024.10.03.616401","title":"LIET Model: Capturing the kinetics of RNA polymerase from loading to termination","abstract":"Abstract Transcription by RNA polymerases is an exquisitely regulated step of the central dogma. Transcription is the primary determinant of cell-state, and most cellular perturbations impact transcription by altering polymerase activity. Thus, detecting changes in polymerase activity yields insight into most cellular processes. Nascent run-on sequencing provides a direct readout of polymerase activity, but no tools exist to model this activity at genes. We focus on RNA polymerase II—responsible for transcribing protein-coding genes. We present the first model to capture the complete process of gene transcription. For individual genes, this model parameterizes each distinct stage of transcription— Loading, Initiation, Elongation , and Termination , hence LIET—in a biologically interpretable Bayesian mixture, which is applied to nascent run-on data. Our improved modeling of Loading / Initiation demonstrates these are characteristically different between sense and antisense strands. Applying LIET to 24 human cell-types, our analysis indicates the position of dissociation (the last step of Termination ) appears to be highly consistent, indicative of a highly regulated process. Furthermore, applying LIET to perturbation experiments, we demonstrate its ability to detect specific changes in pausing (5 ′ end), strand-bias, and dissociation location (3 ′ end)—opening the door to differential assessment of transcription at individual stages of individual genes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":504315,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1354862,"name":"G. Barone","orcid":"0009-0006-6326-4902","position":1,"is_corresponding":false},{"id":923467,"name":"Hope A. Townsend","orcid":"0009-0001-5998-3369","position":2,"is_corresponding":false},{"id":557260,"name":"Rutendo F. Sigauke","orcid":"0000-0001-5882-4377","position":3,"is_corresponding":false},{"id":625949,"name":"Mary A. Allen","orcid":"0000-0001-7490-0165","position":4,"is_corresponding":false},{"id":28295,"name":"Robin D. Dowell","orcid":"0000-0001-7665-9985","position":5,"is_corresponding":false},{"id":557259,"name":"Jacob T. Stanley","orcid":"0000-0002-5652-727X","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T02:10:39.578471Z","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":[]}