Project description:Most individuals infected with Mycobacterium tuberculosis can control the infection by forming and maintaining TB granulomas at the local infection foci. However, when the chronic infection (also known as latency) becomes active, the caseous center of TB granuloma enlarges, and it liquefies and cavitates, ultimately releasing bacilli into airway. Deciphering how genes are regulated within TB granulomas will help to understand the granuloma biology. Therefore, we performed genome-wide microarray on caseous human pulmonary TB granulomas and compared with normal lung tissues.
Project description:Diagnostic tests for tuberculosis (TB) infection poorly predict future incident disease risk. We investigated a cohort of asymptomatic HIV-uninfected household contacts of TB in South Africa in which baseline lung lesions indicative of Subclinical TB identified by [18F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission/computed tomography (PET/CT) had high predictive value for future TB over 5 years. RNA-sequencing analysis of whole blood samples at baseline PET/CT, 5-15m PET/CT2, and the TB diagnosis of incident TB revealed persistent enrichment of neutrophil and monocyte transcriptional modules in those with Subclinical TB and worsening and discrete lung abnormalities, while expression of a core set of type I IFN genes related to FDG-avid lymph nodes. Leveraging multiple machine learning algorithms, we derived gene signatures of various PET/CT lesion Subclinical phenotypesTB, future lesion worsening and TB diagnosis. prevalent and incident TB. Validating signatures in two independent cohorts against TB progression within 6,12,18 and fup to 24-29-months, confirmed gave AUC of 0.75-0.95 and 0.77-0.87 with performance above optimal sensitivity and wminimum specificity for the WHO target product profile for TB progression.
Project description:Diagnostic tests for tuberculosis (TB) infection poorly predict future incident disease risk. We investigated a cohort of asymptomatic HIV-uninfected household contacts of TB in South Africa in which baseline lung lesions indicative of Subclinical TB identified by [18F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission/computed tomography (PET/CT) had high predictive value for future TB over 5 years. RNA-sequencing analysis of whole blood samples at baseline PET/CT, 5-15m PET/CT2, and the TB diagnosis of incident TB revealed persistent enrichment of neutrophil and monocyte transcriptional modules in those with Subclinical TB and worsening and discrete lung abnormalities, while expression of a core set of type I IFN genes related to FDG-avid lymph nodes. Leveraging multiple machine learning algorithms, we derived gene signatures of various PET/CT lesion Subclinical phenotypesTB, future lesion worsening and TB diagnosis. prevalent and incident TB. Validating signatures in two independent cohorts against TB progression within 6,12,18 and fup to 24-29-months, confirmed gave AUC of 0.75-0.95 and 0.77-0.87 with performance above optimal sensitivity and wminimum specificity for the WHO target product profile for TB progression.
Project description:Most individuals infected with Mycobacterium tuberculosis can control the infection by forming and maintaining TB granulomas at the local infection foci. However, when the chronic infection (also known as latency) becomes active, the caseous center of TB granuloma enlarges, and it liquefies and cavitates, ultimately releasing bacilli into airway. Deciphering how genes are regulated within TB granulomas will help to understand the granuloma biology. Therefore, we performed genome-wide microarray on caseous human pulmonary TB granulomas and compared with normal lung tissues. Laser capture microdissection (LCM) was used to dissect out caseous granulomas from TB patients' lung tissues, excluding uninvolved areas. Total RNA were isolated from LCM-derived materials and used for microarray. As a control, parenchyma from normal lung tissues was prepared in the same manner as caseous granulomas. Sample GSM501252, Caseum 2-C, is missing a CEL file.
