Abstract
The term “omics” refers to collective high-throughput approaches that include genomics, transcriptomics, proteomics and metabolomics. Primary focus of OMIC technologies includes identification of genes and genomic variants (genomics), mRNA expression levels (transcriptomics), proteins (proteomics) and low molecular weight metabolites (metabolomics) in cell or tissue type. Omics technologies may lead to detection of the novel molecular signatures (gene/protein/metabolites) which are specific to disease and may serve as a promising candidate for early diagnosis, prediction of therapeutic response and prognosis of disease. Individually, these technologies have contributed significantly towards medical advances. Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the deadly diseases, and worldwide millions of people suffer from TB and die every year. Diagnostics constitutes the most important component of TB control programme, and in recent years considerable progress has been made in the field of TB diagnosis. However, a rapid, cost-effective point-of-care (POC) diagnostic test for different forms of tuberculosis is still lacking. In this context, recent advancements utilising the multidimensional omic approach including genomics, transcriptomics and proteomics provide an improved platform for discovering the key molecular signatures to facilitate TB diagnostics and predicting treatment response. Utilising advanced and integrated omics technologies, recently there has been a tremendous progress in the field of biomarker discovery for TB diagnostics to achieve the goals set by the World Health Organization (WHO) End TB Strategy and the Foundation for Innovative New Diagnostics (FIND) Strategy for tuberculosis. This chapter is focused on various TB diagnostics based on various omics approaches with main emphasis on genomics and proteomics.
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References
Abhishek S, Saikia UN, Gupta A, Bansal R, Gupta V, Singh N, Laal S, Verma I (2018) Transcriptional profile of Mycobacterium tuberculosis in an in vitro model of intraocular tuberculosis. Front Cell Infect Microbiol 8:330. https://doi.org/10.3389/fcimb.2018.00330
Abhishek S, Ryndak MB, Choudhary A, Sharma S, Gupta A, Gupta V, Singh N, Laal S, Verma I (2019) Transcriptional signatures of Mycobacterium tuberculosis in mouse model of intraocular tuberculosis. Pathog Dis 77(5):ftz045. https://doi.org/10.1093/femspd/ftz045
Achkar JM, Cortes L, Croteau P, Yanofsky C, Mentinova M, Rajotte I, Schirm M et al (2015) Host protein biomarkers identify active tuberculosis in HIV uninfected and co-infected individuals. EBioMedicine 2:1160–1168
Agranoff D, Fernandez-Reyes D, Papadopoulos MC, Rojas SA, Herbster M, Loosemore A et al (2006) Identification of diagnostic markers for tuberculosis by proteomic fingerprinting of serum. Lancet 368:1012–1021
Bansal R, Khan MM, Dasari S, Verma I, Goodlett DR, Manes NP et al (2020) Proteomic profile of vitreous in patients with tubercular uveitis. Tuberculosis 126:102036
Bentley SI, Quan X, Newman T, Huygen K, Godfrey HP (1999) Pathophysiology of antigen 85 in patients with active tuberculosis: antigen 85 circulates as complexes with fibronectin and immunoglobulin G. Infect Immun 67:581–588
Berry MPR, Graham CM et al (2010) An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 466:973–977
Branigan D (2020) The tuberculosis diagnostics pipeline report: advancing the next generation of tools. Treatment Action Group, New York
Cao Y, Parmar H, Gaur RL, Lieu D, Raghunath S, Via N, Battagalia S, Cirillo DM, Denkinger C, Georghiou S et al (2020) Xpert MTB/XDR: a ten-color reflex assay suitable for point of care settings to detect isoniazid, fluoroquinolone, and second-line injectable drug-resistance directly from mycobacterium tuberculosis positive sputum. J Clin Microbiol 59(3):e02314–e02320. https://doi.org/10.1128/JCM.02314-20
Chen J, Han Y, Yi W, Huang H, Li Z, Shi L et al (2020) Serum CD14, PGLYRP2 and FGA as potential biomarkers for multidrug-resistant tuberculosis based on data-independent acquisition and targeted proteomics. J Cell Mol Med 24:12537–12549
Cho Y, Park Y, Sim B et al (2020) Identification of serum biomarkers for active pulmonary tuberculosis using a targeted metabolomics approach. Sci Rep 10:3825. https://doi.org/10.1038/s41598-020-60669-0
Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D et al (1998) Deciphering the biology of mycobacterium tuberculosis from the complete genome sequence. Nature 393(6685):537–544. https://doi.org/10.1038/31159
Combrink M, Preez I, Ronacher K, Walzl G, Loots D (2019) Time-dependent changes in urinary metabolome before and after intensive phase tuberculosis therapy: a pharmacometabolomics study. OMICS 23(11):560–572. https://doi.org/10.1089/omi.2019.0140
De Welzen L, Eldholm V, Maharaj K, Manson AL, Earl AM, Pym AS (2017) Whole-transcriptome and -genome analysis of extensively drug-resistant mycobacterium tuberculosis clinical isolates identifies downregulation of ethA as a mechanism of ethionamide resistance. Antimicrob Agents Chemother 61(12):e01461–e01417
Dutta NK, Tornheim JA, Fukutani KF, Paradkar M et al (2020) Integration metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children. Sci Rep 10:19527. https://doi.org/10.1038/s41598-020-75513-8
Garay-Baquero WC, Walker N et al (2020) Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis. JCI Insight 5(18):e137427. https://doi.org/10.1172/jci.insight.137427
Gengenbacher M, Kaufmann SH (2012) Mycobacterium tuberculosis: success through dormancy. FEMS Microbiol Rev 36(3):514–532. Epub 2012 Mar 8. https://doi.org/10.1111/j.1574-6976.2012.00331.x
Gomez-Gonzalez PJ, Andreu N, Phelan JE et al (2019) An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome. Sci Rep 9:5204. https://doi.org/10.1038/s41598-019-41692-2
Grønningen E, Sviland L, Ngadaya E, Nanyaro M, Muller W, Torres L, Mfinanga S, Mustafa T (2019) Utility of MPT64 antigen detection test for diagnosis of HIV coinfected extrapulmonary tuberculosis in Tanzania. Eur Respir J 54(Suppl 63):PA560. https://doi.org/10.1183/13993003.congress-2019.PA560
Haas CT, Jennifer KR, Pollara G, Mehta M, Mahdad N et al (2016) Diagnostic ‘omics’ for active tuberculosis. BMC Med 14:37
Hoel IM, Sviland L, Syre H et al (2020) Diagnosis of extrapulmonary tuberculosis using the MPT64 antigen detection test in a high-income low tuberculosis prevalence setting. BMC Infect Dis 20:130. https://doi.org/10.1186/s12879-020-4852-z
Jajou R, Laan TV, Zwaan R, Kamst M, Mulder A, Neeling A, Anthony R, Soolingen D (2019) WGS more accurately predicts susceptibility of mycobacterium tuberculosis to first-line drugs than phenotypic testing. J Antimicrob Chemother 74(9):2605–2616
Jakhar S, Bitzer AA, Stromberg LR, Mukundan H (2020) Pediatric tuberculosis: the impact of “omics” on diagnostics development. Int J Mol Sci 21:6979. https://doi.org/10.3390/ijms21196979
Jena L, Wankhade G, Waghmare P et al (2016) Pharmacoproteomics genomics and proteomics of virulent, avirulent and drug resistant strains of tuberculous mycobacteria. Pharmacoproteomics 7:159
Jiang J, Yang J, Shi Y, Jin Y, Tang S, Zhang N et al (2020) Head-to-head comparison of the diagnostic accuracy of Xpert MTB/RIF and Xpert MTB/RIF ultra for tuberculosis: a meta-analysis. Infect Dis 52(11):763–775. https://doi.org/10.1080/23744235.2020.1788222
Kashyap RS, Rajan AN, Ramteke SS, Agrawal VS, Kelkar SS, Purohit HJ, Taori GM, Daginawala HF (2007) Diagnosis of tuberculosis in an Indian population by an indirect ELISA protocol based on detection of antigen 85 complex: a prospective cohort study. BMC Infect Dis 7:74
Kidneya BR, Kabangila R, Peck RN, Mshana SE, Webster LE, Koenig SP (2013) Early and efficient detection of mycobacterium tuberculosis in sputum by microscopic observations of broth culture. PLoS One 8:e57527
Kohli M, MacLean E, Pai M, Schumacher SG, Denkinger CM (2020) Diagnostic accuracy of centralised assays for TB detection and detection of resistance to rifampicin and isoniazid: a systematic review and meta-analysis. Eur Respir J 57(2):2000747. https://doi.org/10.1183/13993003.00747-2020
Kumari P, Lavania S, Tyagi S, Dhiman A, Rath R, Anthwal D, Gupta RK, Sharma N et al (2018) A novel aptamer-based test for the rapid and accurate diagnosis of pleural tuberculosis. Anal Biochem 564–565:86–87
Lavania S, Das R, Dhiman A, Myneedu VP, Verma A, Singh N, Sharma TK, Tyagi JS (2018) Aptamer-based TB antigen tests for the rapid diagnosis of pulmonary tuberculosis: potential utility in screening for tuberculosis. ACS. Infect Dis 4(12):1718–1726. https://doi.org/10.1021/acsinfecdis.8b00201
Lee SW, Wu LH, Huang GM, Huang KY, Lee TY, Weng JTY (2016) Gene expression profiling identifies candidate biomarkers for active and latent tuberculosis. BMC Bioinform 17:S3. https://doi.org/10.1186/s12859-015-0848-x
Lombardi G, Pellegrino MT, Denicolò A, Corsini I, Tadolini M, Bergamini BM, Meacci M, Garazzino S, Peracchi S, Lanari M, Re MC, Monte PD (2019) QuantiFERON-TB performs better in children, including infants, than in adults with active tuberculosis: a multicenter study. J Clin Microbiol 57(10):e01048–e01019. https://doi.org/10.1128/JCM.01048-19
Mateos J, Estévez O, González-Fernández Á, Anibarro L, Pallarés Á, Reljic R, Gallardo JM, Medina I, Carrera M (2019) High-resolution quantitative proteomics applied to the study of the specific protein signature in the sputum and saliva of active tuberculosis patients and their infected and uninfected contacts. J Proteomics 19541–19552. https://doi.org/10.1016/j.jprot.2019.01.010
Meehan CJ, Goig GA, Kohl TA, Verboven L, Dippenar A et al (2019) Whole genome sequencing of mycobacterium tuberculosis: current standards and open issues. Nat Rev Microbiol 17(9):533–545
Mehaffy C, KruhGarcia NA, Graham B, Jarlsberg LG, Willyerd CE, Borisov A, Sterling TR, Nahid P, Dobos KM (2020) Identification of mycobacterium tuberculosis peptides in serum extracellular vesicles from persons with latent tuberculosis infection. J Clin Microbiol 58:e00393–e00320. https://doi.org/10.1128/JCM.00393-20
Meier N, Marc J, Ottenhoff HM, Nicole R (2018) A systematic review on novel mycobacterium tuberculosis antigens and their discriminatory potential for the diagnosis of latent and active tuberculosis. Front Immunol 9:2476. https://doi.org/10.3389/fimmu.2018.02476
Pan L, Zhang X, Jia H, Huang M, Liu F, Wang X et al (2020) Label-free quantitative proteomics identifies novel biomarkers for distinguishing tuberculosis pleural effusion from malignant pleural effusion. Proteomics Clin Appl 14(1):e1900001
Peng Z, Chen L, Zhang H (2020) Serum proteomic analysis of mycobacterium tuberculosis antigens for discriminating active tuberculosis from latent infection. J Int Med Res 48(3):1–14
Penn A, Hraha T, ThompsonEG SD, Mbandi SK, Wall KM et al (2019) Discovery and validation of a prognostic proteomic signature for tuberculosis progression: a prospective cohort study. PLoS Med 16(4):e1002781. https://doi.org/10.1371/journal.pmed.1002781
Penn-Nicholson A, Mbandi SK, Thompson E et al (2020) RISK6, a 6-gene transcriptomic signature of TB disease RISK, diagnosis and treatment response. Sci Rep 10:8629. https://doi.org/10.1038/s41598-020-65043-8
Roe J, Venturini C, Gupta RK et al (2020) Blood transcriptomic stratification of short-term risk in contacts of tuberculosis. Clin Infect Dis 70(5):731–737. https://doi.org/10.1093/cid/ciz252
Sambarey A, Devaprasad A, Mohan A, Ahmed A, Nayak S, Swaminathan S et al (2016) Unbiased identification of blood-based biomarkers for pulmonary tuberculosis by modeling and mining molecular interaction networks. EBioMedicine 15:112–116. https://doi.org/10.1016/j.ebiom.2016.12.009
Schwander S, Dheda K (2010) Human lung immunity against mycobacterium tuberculosis: insights into pathogenesis and protection. Am J Respir Crit Care Med 183(6):696–707. Epub 2010 Nov 12. https://doi.org/10.1164/rccm.201006-0963PP
Seo YS, Kang JM, Kim DS, Ahn JG (2020) Xpert MTB/RIF assay for diagnosis of extrapulmonary tuberculosis in children: a systematic review and meta-analysis. BMC Infect Dis 20:14. https://doi.org/10.1186/s12879-019-4745-1
Sharma S, Ryndak MB, Aggarwal AN, Yadav R, Sethi S, Masih S, Laal S, Verma I (2017) Transcriptome analysis of mycobacteria in sputum samples of pulmonary tuberculosis patients. PLoS One 12(3):e0173508. https://doi.org/10.1371/journal.pone.0173508
Sharma V, Soni H, Kumar P, Dawra S, Mishra S, Mandavdhare HS, Singh H, Dutta U (2020) Diagnostic accuracy of the Xpert MTB/RIF assay for abdominal tuberculosis: a systematic review and meta-analysis. Expert Rev Anti Infect Ther 19(2):253–265. https://doi.org/10.1080/14787210.2020.1816169
Shete PB, Farr K, Strnad L, Gray CM, Cattamanchi A (2019) Diagnostic accuracy of TB-LAMP for pulmonary tuberculosis: a systematic review and meta-analysis. BMC Infect Dis 19:268. https://doi.org/10.1186/s12879-019-3881-y
Shin JA, Chang YS, Kim HJ, Ahn CM, Byun MK (2015) Diagnostic utility of interferon-gamma release assay in extrapulmonary tuberculosis. Diagn Microbiol Infect Dis 82(1):44–48. https://doi.org/10.1016/j.diagmicrobio.2015.02.002
Singh P, Kanade S, Nataraj G (2019) Sensitivity and specificity of loop-mediated isothermal amplification assay for diagnosis of extra-pulmonary tuberculosis: a cross-sectional study. Eur Respir J 54(63):PA554. https://doi.org/10.1183/13993003.congress-2019.PA554
Singhania A, Verma R, Graham CM, Lee J, Tran T, Richardson M et al (2018) A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection. Nat Commun 9:2308. https://doi.org/10.1038/s41467-018-04579-w
Soundararajan L, Kambli P, Priyadarshini S, Let B, Murugan S, Iravatham C et al (2020) Whole genome enrichment approach for rapid detection of mycobacterium tuberculosis and drug resistance-associated mutations from direct sputum sequencing. Tuberculosis 121:101915
Suliman S, Thompson E, Sutherland J et al (2018) Four-gene pan-African blood signature predicts progression to tuberculosis. Am J Respir Crit Care Med 197:1198–1208
Sweeney TE, Braviak L, Tato CM, Khatri P (2016) Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis. Lancet Respir Med 4:213–224. https://doi.org/10.1016/S2213-2600(16)00048-5
Sypabekova M, Bekmurzayeva A, Wang R, Li Y, Nogues C, Kanayeva D (2017) Selection, characterization, and application of DNA aptamers for detection of mycobacterium tuberculosis secreted protein MPT64. Tuberculosis 104:70–78
Tadesse M, Abebe G, Bekele A, Bezabih M, Yilma D, Apers L, Jong BC, Rigouts L (2019) Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a diagnostic evaluation study. Clin Microbiol Infect 25(8):1000–1005. https://doi.org/10.1016/j.cmi.2018.12.018
Tang J, Zhihao L, Ya'nan S, Lingjun Z, Chuan Q (2020) Whole genome and transcriptome sequencing of two multi-drug resistant mycobacterium tuberculosis strains to facilitate illustrating their virulence in vivo. Front Cell Infect Microbiol 10:219. https://doi.org/10.3389/fcimb.2020.00219
Tripathi DK, Srivastava K, Nagpal KL, Shukla PK, Srivastava KK (2019) Exploration of some new secretory proteins to be employed for companion diagnosis of mycobacterium tuberculosis. Immunol Lett 209:67–74., ISSN 0165-2478. https://doi.org/10.1016/j.imlet.2019.03.010
Vander Werf MJ, Kodmon C (2019) Whole-genome sequencing as tool for investigating international tuberculosis outbreaks: a systematic review. Front Public Health 7:87
Vaquer AA, Rizvi A, Matzapetakis M, Lamosa P, Coelho AV et al (2019) Active and prospective latent tuberculosis are associated with different metabolomic profiles: clinical potential for the identification of rapid and non-invasive biomarkers. Emerg Microb Infect 9(1):1131–1139. https://doi.org/10.1080/22221751.2020.1760734
Wang MG, Xue M, Wu SQ, Zhang MM, Wang Y, Liu Q, Sandford AJ, He JQ (2019) Abbott RealTime MTB and MTB RIF/INH assays for the diagnosis of tuberculosis and rifampicin/ isoniazid resistance. Infect Genet Evol 71:54–59. https://doi.org/10.1016/j.meegid.2019.03.012
Wang WH, Takeuchi R, Jain SH, Jiang YH, Watanuki S et al (2020) A novel, rapid (within hours) culture-free diagnostic method for detecting live mycobacterium tuberculosis with high sensitivity. EBioMedicine 60:19–28
Warsinske H, Vashisht R, Khatri P (2019) Host-response-based gene signatures for tuberculosis diagnosis: a systematic comparison of 16 signatures. PLoS Med 16(4):e1002786. https://doi.org/10.1371/journal.pmed.1002786
WHO (2011) Commercial serodiagnostic tests for diagnosis of tuberculosis. Policy statement. WHO, Geneva
WHO (2015) The End TB strategy. WHO, Geneva. http://www.who.int/tb/strategy/en/
WHO (2016) The use of loop-mediated isothermal amplification (TB-LAMP) for the diagnosis of pulmonary tuberculosis: Policy guidance. World Health Organization, Geneva
WHO (2019) Lateral flow urine lipoarabinomannan assay (LF-LAM) for the diagnosis of active tuberculosis in people living with HIV: Policy update. WHO, Geneva
WHO (2020a) Global TB Rep 2020. WHO, Geneva
WHO (2020b) WHO consolidated guidelines on tuberculosis. Module 3: diagnosis—rapid diagnostics for tuberculosis detection. World Health Organization, Geneva. Licence: CC BY-NC-SA 3.0 IGO
World Health Organization (2008) Molecular line probe assay for rapid screening of patients at risk of multidrug-resistant tuberculosis (MDR-TB). World Health Organization, Policy statement
Wildner LM, Gould KA, Waddell SJ (2018) Transcriptional profiling Mycobacterium tuberculosis from patient sputa. Methods Mol Biol 1736:117–128. https://doi.org/10.1007/978-1-4939-7638-6_11
Yang Y, Wu J (2019) Significance of the differential peptidome in multidrug-resistant tuberculosis. Bio Med Res Int 2019:5653424. https://doi.org/10.1155/2019/5653424
Young BL, Mlamla Z, Gqamana PP, Smit S, Roberts T, Peter J, Theron G, Govender U, Dheda K, Blackburn J (2014) The identification of tuberculosis biomarkers in human urine samples. Eur Respir J 43:1719–1729
Zak DE, Penn NA, Scriba TJ et al (2016) A blood RNA signature for tuberculosis disease risk: a prospective cohort study. Lancet 387:2312–2322
Zhang E, Xue M, He J (2020) Diagnostic accuracy of the new Xpert MTB/RIF ultra for tuberculosis disease: a preliminary systematic review and meta-analysis. Int J Infect Dis 90:35–45. https://doi.org/10.1016/j.ijid.2019.09.016
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Verma, I., Kaur, K. (2022). Omics in Tuberculosis Diagnosis: Today and Tomorrow. In: Sobti, R., Sobti, A. (eds) Biomedical Translational Research. Springer, Singapore. https://doi.org/10.1007/978-981-16-4345-3_13
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