Comprehensive analyses of potential key genes in active tuberculosis

Chen, Jiarui; Liu, Chong; Liang, Tuo; Xu, Guoyong; Zhang, Zide; Lu, Zhaojun; Jiang, Jie; Chen, Tianyou; Li, Hao; Huang, Shengsheng; Chen, Liyi; Xi-hua, Sun; Cen, Jiemei; Zhan, Xinli

doi:10.1097/md.0000000000026582

Cited by 9 publications

(13 citation statements)

References 58 publications

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“…In the brown module, we also identified STAT1 hub-central TF, a pivotal component of the JAK–STAT signaling pathway and a signal transducer and transcription activator that mediates cellular responses to IFNs, cytokines, and growth factors ( Hall et al, 2020 ). Interestingly, M. bovis counteracts the immune response by suppressing STAT1 expression and exacerbates its pathogenesis in the host cells ( Chen J. et al, 2021 ). Studies in patients with active TB have shown that STAT1 activation was impaired in host macrophages ( Esquivel-Solís et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

“…Bovine tuberculosis (bTB) is domestic livestock's infectious and chronic respiratory disease, especially in beef and dairy cattle (Brosch et al, 2002;Waters et al, 2012;Hall et al, 2021), which has paramount economic, animal welfare, and public health consequences. Despite implementing management strategies to control and eradicate it, bTB is still a major global health threat to animal populations (Vegh et al, 2015;Lu et al, 2021). Econometric analysis has ranked bTB as the fourth most important cattle disease, causing ~$3 billion in annual losses to global agriculture (Garnier et al, 2003;McLoughlin et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

et al. 2022

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ObjectiveBovine tuberculosis (bTB) is a chronic respiratory infectious disease of domestic livestock caused by intracellular Mycobacterium bovis infection, which causes ~$3 billion in annual losses to global agriculture. Providing novel tools for bTB managements requires a comprehensive understanding of the molecular regulatory mechanisms underlying the M. bovis infection. Nevertheless, a combination of different bioinformatics and systems biology methods was used in this study in order to clearly understand the molecular regulatory mechanisms of bTB, especially the immunomodulatory mechanisms of M. bovis infection.MethodsRNA-seq data were retrieved and processed from 78 (39 non-infected control vs. 39 M. bovis-infected samples) bovine alveolar macrophages (bAMs). Next, weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression modules in non-infected control bAMs as reference set. The WGCNA module preservation approach was then used to identify non-preserved modules between non-infected controls and M. bovis-infected samples (test set). Additionally, functional enrichment analysis was used to investigate the biological behavior of the non-preserved modules and to identify bTB-specific non-preserved modules. Co-expressed hub genes were identified based on module membership (MM) criteria of WGCNA in the non-preserved modules and then integrated with protein–protein interaction (PPI) networks to identify co-expressed hub genes/transcription factors (TFs) with the highest maximal clique centrality (MCC) score (hub-central genes).ResultsAs result, WGCNA analysis led to the identification of 21 modules in the non-infected control bAMs (reference set), among which the topological properties of 14 modules were altered in the M. bovis-infected bAMs (test set). Interestingly, 7 of the 14 non-preserved modules were directly related to the molecular mechanisms underlying the host immune response, immunosuppressive mechanisms of M. bovis, and bTB development. Moreover, among the co-expressed hub genes and TFs of the bTB-specific non-preserved modules, 260 genes/TFs had double centrality in both co-expression and PPI networks and played a crucial role in bAMs-M. bovis interactions. Some of these hub-central genes/TFs, including PSMC4, SRC, BCL2L1, VPS11, MDM2, IRF1, CDKN1A, NLRP3, TLR2, MMP9, ZAP70, LCK, TNF, CCL4, MMP1, CTLA4, ITK, IL6, IL1A, IL1B, CCL20, CD3E, NFKB1, EDN1, STAT1, TIMP1, PTGS2, TNFAIP3, BIRC3, MAPK8, VEGFA, VPS18, ICAM1, TBK1, CTSS, IL10, ACAA1, VPS33B, and HIF1A, had potential targets for inducing immunomodulatory mechanisms by M. bovis to evade the host defense response.ConclusionThe present study provides an in-depth insight into the molecular regulatory mechanisms behind M. bovis infection through biological investigation of the candidate non-preserved modules directly related to bTB development. Furthermore, several hub-central genes/TFs were identified that were significant in determining the fate of M. bovis infection and could be promising targets for developing novel anti-bTB therapies and diagnosis strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

et al. 2022

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“…Within macrophages, intracellular Mtb can promote NF-κB pathway activation, in turn leading to GBP induction and the inhibition of caspase-3 activation, thus preventing macrophages from undergoing apoptotic death such that Mtb can thrive and replicate within these host cells [30]. Multiple reports have shown Mtb infection to be linked to the upregulation of a range of GBPs including GBP1-7, with elevated levels of these genes being linked to the risk of disease progression [31,32]. ATF3 (activating transcription factor 3) is an ATF/cAMP response element-binding transcription factor that can reportedly modulate the upregulation of proinflammatory cytokines through binding to the NF-κB p65 subunit [33].…”

Section: Discussionmentioning

confidence: 99%

Coexpression Network Analysis-Based Identification of Critical Genes Differentiating between Latent and Active Tuberculosis

Chen

Hua

2022

Disease Markers

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Background and Objectives. The identification of reliable biomarkers is critical to the diagnosis and prevention of progression from latent tuberculosis infection (LTBI) to active tuberculosis (ATB). This study was thus developed to identify key hub genes capable of differentiating between LTBI and ATB through a weighted gene coexpression network analysis (WGCNA) approach. Methods. Three Gene Expression Omnibus (GEO) microarray datasets (GSE19491, GSE98461, and GSE152532) were downloaded, with GSE19491 and GSE98461 then being merged to form a training dataset. Hub genes capable of differentiating between ATB and LTBI were then identified through differential expression analyses and a WGCNA analysis of this training dataset. Receiver operating characteristic (ROC) curves were then used to gauge to the diagnostic accuracy of these hub genes in the test dataset (GSE152532). Gene expression-based immune cell infiltration and the relationship between such infiltration and hub gene expression were further assessed via a single-sample gene set enrichment analysis (ssGSEA). Results. In total, 485 differentially expressed genes were analyzed, with the WGCNA approach yielding 8 coexpression models. Of these, the black module was the most closely correlated with ATB. In total, five hub genes (FBXO6, ATF3, GBP1, GBP4, and GBP5) were identified as potential biomarkers associated with LTBI progression to ATB based on a combination of differential expression and LASSO analyses. The area under the ROC curve values for these five genes ranged from 0.8 to 0.9 in the test dataset, and ssGSEA revealed the expression of these genes to be negatively correlated with lymphocyte activity but positively correlated with myeloid and inflammatory cell activity. Conclusion. The five hub genes identified in this study may play a novel role in tuberculosis-related immunopathology and offer value as novel biomarkers differentiating LTBI from ATB.

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“…Los resultados experimentales obtenidos por los investigadores indicaron que los tubos de calor super largos con una relación L/D extremadamente grande, pueden trabajar con un correcto funcionamiento. Chen et al [10] realizó un estudio experimental sobre un tubo de calor extralargo asistido por gravedad de gran relación L/D (>5000),donde se observan los regímenes de flujo multifásico al interior del tubo de calor y como estos se relacionaban como el rendimiento del dispositivo. En base a los resultados de la experimentación, se observó que el termosifón super largo funciona en cuatro regímenes de flujo distintos, uno de ellos provocado directamente por la alta relación L/D utilizada.…”

Section: Introductionunclassified

“…El régimen de ebullición en géiser donde la temperatura de la superficie muestra fluctuación periódica. La ebullición en géiser es más probable que ocurra en tubos de calor super largos con alta relación L/D [10]. La ebullición en géiser es un fenómeno de inestabilidad que pueden presentar los termosifones, está relacionada con la expansión abrupta del vapor en el evaporador [11].…”

Section: Introductionunclassified

Estudio experimental de termosifones bifásicos con relación largo-diámetro interno constante para aplicaciones geotérmicas

2022

Congreso Iberoamericano De Ingeniería Mecánica-Cibim 2022

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En este trabajo se estudió experimentalmente la validez de la relación largo-diámetro interno (L/D) como herramienta de escalamiento en termosifones bifásicos extralargos para aplicaciones geotérmicas. Fueron estudiados dos termosifones con diferentes dimensiones, manteniendo la relación L/D=110. Los resultados obtenidos muestran que el termosifón de menor tamaño y mayor diámetro operó a temperaturas de vapor mayores (hasta de 20ºC) y resistencias térmicas menores (hasta 40%), mostrando que la relación L/D no es suficiente para escalar termosifones sin perder informaciones fundamentales de la operación de estos dispositivos. Fue propuesta una longitud característica, dada por D 2 /L, permite reducir significativamente las diferencias entre las resistencias térmicas de ambos termosifones. Sin embargo, se sugiere que el escalamiento de termosifones bifásicos extralargos no envuelva solo aspectos geométricos del dispositivo, sino que también incluya propiedades termofísicas del fluido de trabajo, las cuales son afectadas significativamente por la temperatura de operación del vapor.

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Comprehensive analyses of potential key genes in active tuberculosis

Cited by 9 publications

References 58 publications

In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

Coexpression Network Analysis-Based Identification of Critical Genes Differentiating between Latent and Active Tuberculosis

Estudio experimental de termosifones bifásicos con relación largo-diámetro interno constante para aplicaciones geotérmicas

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