{"doi":"10.3389/fimmu.2021.676980","title":"Integrative Multi-Omics Reveals Serum Markers of Tuberculosis in Advanced HIV","abstract":"Tuberculosis (TB) accounts for disproportionate morbidity and mortality among persons living with HIV (PLWH). Conventional methods of TB diagnosis, including smear microscopy and Xpert MTB/RIF, have lower sensitivity in PLWH. Novel high-throughput approaches, such as miRNAomics and metabolomics, may advance our ability to recognize subclinical and difficult-to-diagnose TB, especially in very advanced HIV. We conducted a case-control study leveraging REMEMBER, a multi-country, open-label randomized controlled trial comparing 4-drug empiric standard TB treatment with isoniazid preventive therapy in PLWH initiating antiretroviral therapy (ART) with CD4 cell counts <50 cells/μL. Twenty-three cases of incident TB were site-matched with 32 controls to identify microRNAs (miRNAs), metabolites, and cytokines/chemokines, associated with the development of newly diagnosed TB in PLWH. Differentially expressed miRNA analysis revealed 11 altered miRNAs with a fold change higher than 1.4 or lower than -1.4 in cases relative to controls (p<0.05). Our analysis revealed no differentially abundant metabolites between cases and controls. We found higher TNFα and IP-10/CXCL10 in cases (p=0.011, p=0.0005), and higher MDC/CCL22 in controls (p=0.0072). A decision-tree algorithm identified gamma-glutamylthreonine and hsa-miR-215-5p as the optimal variables to classify incident TB cases (AUC 0.965; 95% CI 0.925-1.000). hsa-miR-215-5p, which targets genes in the TGF-β signaling pathway, was downregulated in cases. Gamma-glutamylthreonine, a breakdown product of protein catabolism, was less abundant in cases. To our knowledge, this is one of the first uses of a multi-omics approach to identify incident TB in severely immunosuppressed PLWH.","journal":"Frontiers in Immunology","year":2021,"id":161193,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9472,"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":382615,"name":"Artur T. L. Queiroz","orcid":"0000-0003-4908-9993","position":1,"is_corresponding":false},{"id":326405,"name":"Amita Gupta","orcid":"0000-0001-7036-2718","position":2,"is_corresponding":false},{"id":326403,"name":"Nikhil Gupte","orcid":"0000-0002-6688-2478","position":3,"is_corresponding":false},{"id":327408,"name":"Gregory P. Bisson","orcid":null,"position":4,"is_corresponding":false},{"id":913,"name":"Johnstone Kumwenda","orcid":"0000-0003-2622-4339","position":5,"is_corresponding":false},{"id":252303,"name":"Kogieleum Naidoo","orcid":"0000-0002-8874-6661","position":6,"is_corresponding":false},{"id":442631,"name":"Lerato Mohapi","orcid":null,"position":7,"is_corresponding":false},{"id":326404,"name":"Vidya Mave","orcid":"0000-0001-8509-4517","position":8,"is_corresponding":false},{"id":675539,"name":"Rosie Mngqibisa","orcid":"0000-0002-6540-5733","position":9,"is_corresponding":false},{"id":385132,"name":"Javier R. Lama","orcid":"0000-0002-4983-5725","position":10,"is_corresponding":false},{"id":312050,"name":"Mina C. Hosseinipour","orcid":"0000-0003-2174-313X","position":11,"is_corresponding":false},{"id":252301,"name":"Bruno B. Andrade","orcid":"0000-0001-6833-3811","position":12,"is_corresponding":false},{"id":333926,"name":"Petros C. Karakousis","orcid":"0000-0003-1338-9206","position":13,"is_corresponding":false},{"id":675538,"name":"Sonya Krishnan","orcid":"0000-0002-5765-3913","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T23:44:52.299342Z","pmid":"34168648","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":[]}