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      Integrating pathogen- and host-derived blood biomarkers for enhanced tuberculosis diagnosis: a comprehensive review

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          Abstract

          This review explores the evolving landscape of blood biomarkers in the diagnosis of tuberculosis (TB), focusing on biomarkers derived both from the pathogen and the host. These biomarkers provide critical insights that can improve diagnostic accuracy and timeliness, essential for effective TB management. The document highlights recent advancements in molecular techniques that have enhanced the detection and characterization of specific biomarkers. It also discusses the integration of these biomarkers into clinical practice, emphasizing their potential to revolutionize TB diagnostics by enabling more precise detection and monitoring of the disease progression. Challenges such as variability in biomarker expression and the need for standardized validation processes are addressed to ensure reliability across different populations and settings. The review calls for further research to refine these biomarkers and fully harness their potential in the fight against TB, suggesting a multidisciplinary approach to overcome existing barriers and optimize diagnostic strategies. This comprehensive analysis underscores the significance of blood biomarkers as invaluable tools in the global effort to control and eliminate TB.

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          Most cited references144

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          Nucleic acid detection with CRISPR-Cas13a/C2c2

          Jonathan S. Gootenberg, Omar O Abudayyeh, Jeong Wook Lee … (2017)
          Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care pathogen detection, genotyping, and disease monitoring. The RNA-guided, RNA-targeting CRISPR effector Cas13a (previously known as C2c2) exhibits a “collateral effect” of promiscuous RNAse activity upon target recognition. We combine the collateral effect of Cas13a with isothermal amplification to establish a CRISPR-based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity. We use this Cas13a-based molecular detection platform, termed SHERLOCK ( S pecific H igh Sensitivity E nzymatic R eporter Un LOCK ing), to detect specific strains of Zika and Dengue virus, distinguish pathogenic bacteria, genotype human DNA, and identify cell-free tumor DNA mutations. Furthermore, SHERLOCK reaction reagents can be lyophilized for cold-chain independence and long-term storage, and readily reconstituted on paper for field applications.
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            Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6

            Omar Abudayyeh, Max J. Kellner, Julia Joung … (2018)
            Rapid detection of nucleic acids is integral for clinical diagnostics and biotechnological applications. We recently developed a platform termed SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) that combines isothermal pre-amplification with Cas13 to detect single molecules of RNA or DNA. Through characterization of CRISPR enzymology and application development, we report here four advances integrated into SHERLOCKv2: 1) 4-channel single reaction multiplexing using orthogonal CRISPR enzymes; 2) quantitative measurement of input down to 2 aM; 3) 3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxilary CRISPR-associated enzyme; and 4) lateral flow read-out. SHERLOCKv2 can detect Dengue or Zika virus ssRNA as well as mutations in patient liquid biopsy samples via lateral flow, highlighting its potential as a multiplexable, portable, rapid, and quantitative detection platform of nucleic acids.
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              Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection

              Wei Gu, Steve Miller, Charles Y. Chiu (2019)
              Nearly all infectious agents contain DNA or RNA genomes, making sequencing an attractive approach for pathogen detection. The cost of high-throughput or next-generation sequencing has been reduced by several orders of magnitude since its advent in 2004, and it has emerged as an enabling technological platform for the detection and taxonomic characterization of microorganisms in clinical samples from patients. This review focuses on the application of untargeted metagenomic next-generation sequencing to the clinical diagnosis of infectious diseases, particularly in areas in which conventional diagnostic approaches have limitations. The review covers ( a) next-generation sequencing technologies and common platforms, ( b) next-generation sequencing assay workflows in the clinical microbiology laboratory, ( c) bioinformatics analysis of metagenomic next-generation sequencing data, ( d) validation and use of metagenomic next-generation sequencing for diagnosing infectious diseases, and ( e) significant case reports and studies in this area. Next-generation sequencing is a new technology that has the promise to enhance our ability to diagnose, interrogate, and track infectious diseases.
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                Author and article information

                Contributors
                Zhaodong Li: URI : https://loop.frontiersin.org/people/889024Role:
                Yunlong Hu: URI : https://loop.frontiersin.org/people/831728Role:
                Wenfei Wang: URI : https://loop.frontiersin.org/people/2742538Role:
                Fa Zou: Role:
                Jing Yang: URI : https://loop.frontiersin.org/people/2799441Role:
                Wei Gao: Role:
                SiWan Feng: Role:
                Guanghuan Chen: Role:
                Chenyan Shi: Role:
                Yi Cai: URI : https://loop.frontiersin.org/people/1517016Role:
                Guofang Deng: URI : https://loop.frontiersin.org/people/1625699Role:
                Xinchun Chen: URI : https://loop.frontiersin.org/people/2143984Role:
                Journal
                Journal ID (nlm-ta): Front Immunol
                Journal ID (iso-abbrev): Front Immunol
                Journal ID (publisher-id): Front. Immunol.
                Title: Frontiers in Immunology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-3224
                Publication date (Electronic): 09 August 2024
                Publication date Collection: 2024
                Volume: 15
                Electronic Location Identifier: 1438989
                Affiliations
                [1] 1 Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine , Shenzhen, China
                [2] 2 Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School , Shenzhen, China
                [3] 3 National Clinical Research Center for Infectious Disease, The Third People's Hospital of Shenzhen, Southern University of Science and Technology , Shenzhen, China
                [4] 4 Department of Preventive Medicine, School of Public Health, Shenzhen University , Shenzhen, China
                [5] 5 Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital , Shenzhen, China
                Author notes

                Edited by: Ana Maria Gamero, Temple University, United States

                Reviewed by: Marta Alonso-Hearn, Basque Research and Technology Alliance (BRTA), Spain

                Taru S. Dutt, Colorado State University, United States

                *Correspondence: Xinchun Chen, chenxinchun@ 123456szu.edu.cn ; Guofang Deng, jxxk1035@ 123456yeah.net
                Article
                DOI: 10.3389/fimmu.2024.1438989
                PMC ID: 11341448
                SO-VID: 8b0a1d41-6ae9-4e50-bc11-8b52bf967eaa
                Copyright © Copyright © 2024 Li, Hu, Wang, Zou, Yang, Gao, Feng, Chen, Shi, Cai, Deng and Chen
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 27 May 2024
                Date accepted : 24 July 2024
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 144, Pages: 13, Words: 6814
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the Shenzhen Medical Research Fund (Grant No. A2304001), National Key Research and Development Program (Grant No. 2022YFC2302901), Shenzhen Peacock Team (Grant No. KQTD20210811090219022), Shenzhen Basic Research (Key Project, Grant No. JCYJ20220818095610021), Shenzhen Major Technological Breakthrough Project (Grant No. JSGG20220822095200001), Provincial Natural Science Foundation of Guangdong (Grant No. 2022A1515220034), Shenzhen Science and Technology Innovation Foundation (Grant No. JCYJ20210324094614038/JCYJ20220530160207015).
                Categories
                Subject: Immunology
                Subject: Review
                Custom metadata
                section-in-acceptance Microbial Immunology

                ScienceOpen disciplines: Immunology
                Keywords: tuberculosis,mycobacterium tuberculosis,biomarker,blood test,molecular diagnosis
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: tuberculosis, mycobacterium tuberculosis, biomarker, blood test, molecular diagnosis

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