Summary
Blood RNA sequencing enables simultaneous measurement of genome-wide transcripts in circulating leukocytes. Infection can drive changes in these measurements by changes to the cellular composition of circulating and leukocytes or by changes to their gene expression profiles as a result of immune response signaling during their passage through the site of disease or haematopoetic and lymphoid tissues. Bioinformatic analysis of blood transcriptional perturbation associated with infection can be used to infer the immunobiology of infections. These data also offer opportunities for discovery of immune-response biomarkers ranging from single gene transcripts to multi-gene signatures. Our programme of work in this field has mostly focussed on tuberculosis (TB) and acute respiratory viral infections, with the aim of discovery and validation of biomarkers to enable advances in precision medicine by improving diagnosis of prevalent disease, prediction of incident (future) disease and differential responses to treatment, and test of cure.
Our publications on Blood RNA biomarkers in TB
Greenan-Barrett J, Gupta RK, Noursadeghi M. The end of the road for blood RNA biomarkers as triage tests for symptomatic pulmonary tuberculosis among spontaneous sputum producers? Eur Respir J. 2024;64(2):2401365. doi:10.1183/13993003.01365-2024.
Greenan-Barrett J, Mendelsohn SC, Scriba TJ, Noursadeghi M, Gupta RK. Single-gene transcripts for subclinical TB: an individual participant data meta-analysis. medRxiv. July 2024:2024.07.04.24309943. doi:10.1101/2024.07.04.24309943.
Mann T, Minnies S, Gupta RK, Reeve BW, Nyawo G, Palmer Z, Naidoo C, Doubell A, Pecararo A, John T-J, Schubert P, Calderwood CJ, Chandran A, Theron G, Noursadeghi M. Blood RNA signatures outperform CRP triage of tuberculosis lymphadenitis and pericarditis. medRxiv. June 2024. doi:10.1101/2024.06.21.24309099.
Mann T, Gupta RK, Reeve BWP, Ndlangalavu G, Chandran A, Krishna AP, Calderwood CJ, Tshivhula H, Palmer Z, Naidoo S, Mbu DL, Theron G, Noursadeghi M. Blood RNA biomarkers for tuberculosis screening in people living with HIV before antiretroviral therapy initiation: a diagnostic accuracy study. The Lancet Global Health. April 2024. doi:10.1016/S2214-109X(24)00029-9.
Calderwood C, Martinez AS, Greenan-Barrett J, Oguti B, Roe J, Gupta R, Martineau AR, Noursadeghi M. Resolution of blood RNA signatures fails to discriminate sputum culture status after eight weeks of tuberculosis treatment. medRxiv. November 2023:2023.11.24.23298983. doi:10.1101/2023.11.24.23298983.
Rosenheim J, Abebe M, Reece S, Noursadeghi M, Martineau AR. Detection of M. tuberculosis DNA in TB contacts PBMC does not associate with blood RNA signatures for incipient tuberculosis. medRxiv. September 2023. doi:10.1101/2023.09.26.23296131.
Noursadeghi M, Gupta RK. New insights into the limitations of host-transcriptional biomarkers of tuberculosis. Am J Respir Crit Care Med. October 2021. doi:10.1164/rccm.202109-2146ED.
Gupta RK, Noursadeghi M. Blood transcriptomic biomarkers for tuberculosis screening: time to redefine our target populations? Lancet Glob Health. 2021;9(6):e736-e737. doi:10.1016/S2214-109X(21)00088-7.
Turner CT, Gupta RK, Tsaliki E, Roe JK, Mondal P, Nyawo GR, Palmer Z, Miller RF, Reeve BW, Theron G, Noursadeghi M. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. Lancet Respir Med. 2020;8(4):407-419. doi:10.1016/S2213-2600(19)30469-2.
Gupta RK, Turner CT, Venturini C, Esmail H, Rangaka MX, Copas A, Lipman M, Abubakar I, Noursadeghi M. Concise whole blood transcriptional signatures for incipient tuberculosis: A systematic review and patient-level pooled meta-analysis. Lancet Respir Med. 2020. doi.org/10.1016/S2213-2600(19)30282-6.
Roe J, Venturini C, Gupta RK, Gurry C, Chain BM, Sun Y, Southern J, Jackson C, Lipman MC, Miller RF, Martineau A, Abubaker I, Noursadeghi M. Blood transcriptomic stratification of short-term risk in contacts of tuberculosis. Clin Infect Dis. 2019. doi:10.1093/cid/ciz252.
Roe JK, Thomas N, Gil E, Best K, Tsaliki E, Morris‑Jones S, Stafford S, Simpson N, Witt KD, Chain B, Miller RF, Martineau A, Noursadeghi M. Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis. JCI Insight. 2016;1(16). doi:10.1172/jci.insight.87238.
Haas CT, Roe JK, Pollara G, Mehta M, Noursadeghi M. Diagnostic “omics” for active tuberculosis. BMC Med. 2016;14:37. doi:10.1186/s12916-016-0583-9.
Our publications on Blood RNA biomarkers in acute viral infections
Rosenheim J, Gupta RK, Thakker C, Mann T, Bell LC, Broderick CM, Madon K, Papargyris L, Dayananda P, Kwok AJ, Greenan-Barrett J, Wagstaffe HR, Conibear E, Fenn J, Hakki S, Lindeboom RG, Dratvia L, Lemetais B, Weight CM, Venturini C, Kaforou M, Levin M, Kalinova M, Mann A, Catchpole A, Knight JC, Nikolić MZ, Teichmann SA, Killingley B, Barclay W, Chain BM, Lalvani A, Heyderman RS, Chiu C, Noursadeghi M. SARS-CoV-2 human challenge reveals single-gene blood transcriptional biomarkers that discriminate early and late phases of acute respiratory viral infections. medRxiv. January 2023:2023.06.01.23290819. doi:10.1101/2023.06.01.23290819.
Gupta RK, Noursadeghi M. Toward a more generalizable blood RNA signature for bacterial and viral infections. Cell Rep Med. 2022;3(12). doi:10.1016/j.xcrm.2022.100866.
Gupta RK, Rosenheim J, Bell LC, Chandran A, Guerra-Assuncao JA, Pollara G, Whelan M, Artico J, Joy G, Kurdi H, Altmann DM, Boyton R, Maini M, McKnight A, Lambourne J, Cutino-moguel T, Manisty C, Treibel TA, Moon JC, Chain B, Noursadeghi M, COVIDsortium investigators. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study. The Lancet Microbe. 2021. doi:10.1016/S2666-5247(21)00146-4.
Li HK, Kaforou M, Rodriguez-Manzano J, Channon-Wells S, Moniri A, Habgood-Coote D, Gupta RK, Mills EA, Arancon D, Lin J, Chiu Y-H, Pennisi I, Miglietta L, Mehta R, Obaray N, Herberg JA, Wright VJ, Georgiou P, Shallcross LJ, Mentzer AJ, Levin M, Cooke GS, Noursadeghi M, Sriskandan S. Discovery and validation of a three-gene signature to distinguish COVID-19 and other viral infections in emergency infectious disease presentations: a case-control and observational cohort study. The Lancet Microbe. 2021;0(0). doi:10.1016/S2666-5247(21)00145-2.
Sampson D, Yager TD, Fox B, Shallcross L, McHugh L, Seldon T, Rapisarda A, Brandon RB, Navalkar K, Simpson N, Stafford S, Gil E, Venturini C, Tsaliki E, Roe J, Chain B, Noursadeghi M. Blood transcriptomic discrimination of bacterial and viral infections in the emergency department: a multi-cohort observational validation study. BMC Med. 2020;18(1):185. doi:10.1186/s12916-020-01653-3.