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Perspectives for systems biology in the management of tuberculosis
European Respiratory Review ( IF 9.0 ) Pub Date : 2021-05-25 , DOI: 10.1183/16000617.0377-2020
Irina Kontsevaya 1, 2, 3 , Christoph Lange 1, 2, 3 , Patricia Comella-Del-Barrio 4 , Cristian Coarfa 5, 6 , Andrew R DiNardo 7 , Stephen H Gillespie 8 , Matthias Hauptmann 1, 2 , Christoph Leschczyk 1, 2 , Anna M Mandalakas 7 , Antal Martinecz 9, 10, 11 , Matthias Merker 1, 2 , Stefan Niemann 1, 2 , Maja Reimann 1, 2, 3 , Olena Rzhepishevska 12, 13 , Ulrich E Schaible 1, 2 , Katrin M Scheu 1 , Erwin Schurr 14 , Pia Abel Zur Wiesch 9, 10 , Jan Heyckendorf 2, 3, 15
Affiliation  

Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches – human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes – in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.



中文翻译:

结核病管理中系统生物学的观点

结核病的标准化管理可能很快会被个性化、精准的医学指导疗法所取代,这些疗法以系统生物学领域提供的知识为基础。系统生物学是一个快速发展的计算和数学分析领域,对复杂的生物系统进行建模,可以深入了解结核病的潜在机制,识别新的生物标志物,并有助于优化疾病的预防、诊断和治疗。在耐药结核病不断流行的背景下,这些进展至关重要。在这里,我们回顾了关于系统生物学方法作用的现有证据——人类和分枝杆菌基因组学和转录组学、蛋白质组学、脂质组学/代谢组学、免疫表型分析、系统药理学和肠道微生物群——在结核病的管理中,包括预测疾病进展的风险、分枝杆菌毒力和耐药性的严重程度、不良事件、合并症、对治疗的反应和治疗结果。建议、评估、开发和评价分级 (Grading of Recommendations, Assessment, Development and Evaluation, GRADE) 方法的应用表明,目前大多数研究为回答临床相关问题提供的证据确定性“非常低”。有必要对大型前瞻性患者队列进行进一步研究,包括随机临床试验,以评估研究结果在结核病预防和更有效的患者临床管理中的适用性。不良事件、合并症、对治疗的反应和治疗结果。建议、评估、开发和评价分级 (Grading of Recommendations, Assessment, Development and Evaluation, GRADE) 方法的应用表明,目前大多数研究为回答临床相关问题提供的证据确定性“非常低”。有必要对大型前瞻性患者队列进行进一步研究,包括随机临床试验,以评估研究结果在结核病预防和更有效的患者临床管理中的适用性。不良事件、合并症、对治疗的反应和治疗结果。建议、评估、开发和评价分级 (Grading of Recommendations, Assessment, Development and Evaluation, GRADE) 方法的应用表明,目前大多数研究为回答临床相关问题提供的证据确定性“非常低”。有必要对大型前瞻性患者队列进行进一步研究,包括随机临床试验,以评估研究结果在结核病预防和更有效的患者临床管理中的适用性。回答临床相关问题的证据的确定性。有必要对大型前瞻性患者队列进行进一步研究,包括随机临床试验,以评估研究结果在结核病预防和更有效的患者临床管理中的适用性。回答临床相关问题的证据的确定性。有必要对大型前瞻性患者队列进行进一步研究,包括随机临床试验,以评估研究结果在结核病预防和更有效的患者临床管理中的适用性。

更新日期:2021-05-26
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