{"doi":"10.1101/2025.09.01.673540","title":"Accurate and robust classification of\n                  <i>Mycobacterium bovis</i>\n                  -infected cattle using peripheral blood RNA-seq data","abstract":"The zoonotic bacterium, Mycobacterium bovis , causes bovine tuberculosis (bTB) and is closely related to Mycobacterium tuberculosis , the primary cause of human tuberculosis (hTB). Bovine TB remains recalcitrant to eradication in endemic countries where current diagnostics fail to identify all infected animals. While blood-based RNA biomarkers identified through machine learning have shown accurate discrimination of hTB-positive and hTB-negative individuals, similar approaches have not been explored for bTB. Here, we use RNA-seq and machine learning to investigate the utility of peripheral blood mRNA as a host-response biomarker for bTB using data from Ireland, the UK and the US. We identify a 30-gene signature and a 273-gene elastic net classifier that differentiate bTB-positive from bTB-negative cattle, achieving area under the curve (AUC) values of 0.986/0.900 for the former and 0.968/0.938 for the latter in training and testing, respectively. These two classifiers produced high sensitivity and specificity values (≥ 0.853 for both metrics) in the testing set. Additionally, we show that they robustly distinguish bTB+ animals from those infected with other bacterial or viral pathogens (AUC ≥ 0.819). These RNA-based classifiers accurately diagnose bTB and differentiate bTB from other diseases, representing a promising tool for augmenting current diagnostics to advance bTB eradication efforts in endemic regions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":4895,"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":0.0508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-09-04","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":50757,"name":"Adriana Ivich","orcid":null,"position":1,"is_corresponding":false},{"id":50758,"name":"Gillian P. McHugo","orcid":"0000-0001-6920-0041","position":2,"is_corresponding":false},{"id":50759,"name":"Adnan Khan","orcid":"0000-0002-8165-1811","position":3,"is_corresponding":false},{"id":50760,"name":"Thomas J. Hall","orcid":"0000-0002-4116-3506","position":4,"is_corresponding":false},{"id":50761,"name":"Sarah L. F. O’Donnell","orcid":null,"position":5,"is_corresponding":false},{"id":50762,"name":"Carolina N. Correia","orcid":"0000-0002-0821-8245","position":6,"is_corresponding":false},{"id":50763,"name":"John A. Browne","orcid":"0000-0002-7698-9834","position":7,"is_corresponding":false},{"id":50764,"name":"Valentina Riggio","orcid":"0000-0003-0461-2939","position":8,"is_corresponding":false},{"id":50765,"name":"James G. D. Prendergast","orcid":"0000-0001-8916-018X","position":9,"is_corresponding":false},{"id":50766,"name":"Emily L. Clark","orcid":"0000-0002-9550-7407","position":10,"is_corresponding":false},{"id":50767,"name":"Hubert Pausch","orcid":"0000-0002-0501-6760","position":11,"is_corresponding":false},{"id":50768,"name":"Kieran G. Meade","orcid":"0000-0002-3051-8586","position":12,"is_corresponding":false},{"id":50769,"name":"Isobel C. Gormley","orcid":null,"position":13,"is_corresponding":false},{"id":50770,"name":"Eamonn Gormley","orcid":"0000-0003-3900-0393","position":14,"is_corresponding":false},{"id":50771,"name":"Stephen V. Gordon","orcid":"0000-0002-4833-5542","position":15,"is_corresponding":false},{"id":308,"name":"Casey S. Greene","orcid":"0000-0001-8713-9213","position":16,"is_corresponding":false},{"id":50772,"name":"David E. MacHugh","orcid":"0000-0002-8112-4704","position":17,"is_corresponding":false},{"id":50773,"name":"Sarah L. Faherty O’Donnell","orcid":null,"position":18,"is_corresponding":false},{"id":50774,"name":"Isobel Claire Gormley","orcid":"0000-0001-7713-681X","position":19,"is_corresponding":false},{"id":50756,"name":"John F. O’Grady","orcid":"0009-0008-9313-3844","position":0,"is_corresponding":true}],"reference_count":100,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","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":[]}