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. 2022 Feb 24;13:835620. doi: 10.3389/fmicb.2022.835620

TABLE 3.

Summary of high-throughput transcriptomic applications in TB research.

Field in TB research Applications References
Mechanisms of bacterial infection • Characterize Mtb growing in vitro. Fisher et al., 2002; Stewart et al., 2002; Ohno et al., 2003; Bacon et al., 2004; Rustad et al., 2008; Mehra and Kaushal, 2009; Voskuil et al., 2011; Tan et al., 2013; Lin et al., 2016; Saini et al., 2020
• Characterize mutant isogenic strains and clinical isolates. Manganelli et al., 2002; Stewart et al., 2002; Gao et al., 2005; Rose et al., 2013; Eldholm et al., 2014; Gomez-Gonzalez et al., 2019; Saini et al., 2020
• Characterize Mtb infecting cells in vitro. Chaussabel et al., 2003; Schnappinger et al., 2003; Cappelli et al., 2006; Rachman et al., 2006a; Rohde et al., 2007, 2012; Fontán et al., 2008a,b; Zimmermann et al., 2017
• Gene expression changes during in vivo infection. Talaat et al., 2004; Rengarajan et al., 2005; Rachman et al., 2006b; Gautam et al., 2015; Coppola et al., 2016; Sharma et al., 2017; Pisu et al., 2020, 2021
• Biofilm production. Flores-Valdez et al., 2020
Mechanisms of latency • Model of latency in vitro. Sherman et al., 2001; Betts et al., 2002; Park et al., 2003; Bacon et al., 2004; Hampshire et al., 2004; Muttucumaru et al., 2004; Voskuil et al., 2004; Beste et al., 2007; Murphy and Brown, 2007; Balázsi et al., 2008; Deb et al., 2009; McGillivray et al., 2015; Aguilar-Ayala et al., 2017
Mechanisms of host response • Characterize the host immune response to infection, analyzing blood or lung tissue. Berry et al., 2010; Jacobsen et al., 2010; Kim et al., 2010; Maertzdorf et al., 2011a; Ottenhoff et al., 2012; Joosten et al., 2013; Arlehamn et al., 2014; Singhania et al., 2018; Cai et al., 2020; Weiner et al., 2020
• Understand the bases of early clearance. Weiner et al., 2020
• Function of host non-coding regulatory RNA. Liu et al., 2011; Sharbati et al., 2011; Wang et al., 2011
• Dual transcriptomic analysis to comprehend host-bacteria interaction. Fontán et al., 2008a; Rienksma et al., 2015; Zimmermann et al., 2017; Pisu et al., 2020, 2021
Diagnosis • Identify blood biomarkers that differentiate active, latent TB patients or healthy individuals. Jacobsen et al., 2007; Mistry et al., 2007; Berry et al., 2010; Maertzdorf et al., 2011a,b; Anderson et al., 2014; Cai et al., 2014; Zak et al., 2016; Singhania et al., 2018; Estévez et al., 2020
• Biomarkers that differentiate TB from other infectious diseases. Berry et al., 2010; Maertzdorf et al., 2012; Bloom et al., 2013; Kaforou et al., 2013; Anderson et al., 2014; Hoang et al., 2021
• Biomarkers for extrapulmonary TB. Roe et al., 2016
• Biomarkers for HIV-TB coinfection. Kaforou et al., 2013; Anderson et al., 2014
Treatment evolution • Identify biomarkers of success/failure to anti-TB treatment. Berry et al., 2010; Bloom et al., 2012; Ottenhoff et al., 2012; Cliff et al., 2013, 2016; Zak et al., 2016; Thompson et al., 2017; Penn-Nicholson et al., 2020; Tabone et al., 2021
Progression to TBI • Finding biomarkers that predict progression to active TBI. Maertzdorf et al., 2011b; Zak et al., 2016; Scriba et al., 2017; Suliman et al., 2018; Warsinske et al., 2019; Ahmed et al., 2020; Estévez et al., 2020; Gupta et al., 2020; Moreira-Teixeira et al., 2020b; Roe et al., 2020; Burel et al., 2021; Esaulova et al., 2021; Nathan et al., 2021; Tabone et al., 2021
• Characterize patients at risk of recurrent TB. Mistry et al., 2007
Drug resistance and search for novel drugs • Understand mechanisms underlying Mtb single and multi-drug resistance in vitro. Keren et al., 2011; Chatterjee et al., 2013; Knegt et al., 2013; Peñuelas-Urquides et al., 2013; Eldholm et al., 2014; Blondiaux et al., 2017; Zheng et al., 2018
• Identify bacterial candidates for drug targeting. Betts et al., 2002; Talaat et al., 2004; Gao et al., 2005; Cappelli et al., 2006; Rachman et al., 2006b; Murphy and Brown, 2007; Balázsi et al., 2008; Fontán et al., 2008a; Rustad et al., 2008; Deb et al., 2009; Salamon et al., 2014; Defelipe et al., 2016; Aguilar-Ayala et al., 2017; Sharma et al., 2017; Banerjee et al., 2020; Saini et al., 2020
• Unravel the mechanism of action of novel compounds. Boshoff et al., 2004; Waddell et al., 2004; Manjunatha et al., 2009; Foo et al., 2018; Zheng et al., 2018
Vaccines and correlates of protection • BCG vaccination effect Fletcher et al., 2009, 2016; Arts et al., 2018; Cirovic et al., 2020
• Characterization of diverse BCG strains and effect in vaccination. Behr et al., 1999; Brosch et al., 2007; Abdallah et al., 2015
• Profile immune response generated by novel TB vaccine candidates. Zárate-Bladés et al., 2009; Gengenbacher et al., 2016; Hoft et al., 2016; Loxton et al., 2017; Hansen et al., 2018; Santoro et al., 2018; van den Berg et al., 2018; Martínez-Pérez et al., 2021
• Search for correlates of protection for new vaccines design or therapies. Aranday Cortes et al., 2010; Maertzdorf et al., 2011b; Fletcher et al., 2016; Hansen et al., 2018; Weiner et al., 2020; Martínez-Pérez et al., 2021

BCG, Bacillus Calmette-Guérin; HIV, Human Immunodeficiency Virus; Mtb, Mycobacterium tuberculosis; MTBC, Mycobacterium Tuberculosis Complex; TB, Tuberculosis.