Combining bioinformatics and biological detection to identify novel biomarkers for diagnosis and prognosis of pulmonary tuberculosis
SAUDI MEDICAL JOURNAL
Authors: Zhao, Guanren; Luo, Xiaobo; Han, Xue; Liu, Zhen
Abstract
Objectives: To identify the novel and promising indicators for pulmonary tuberculosis (PTB) patients Methods: The study was carried out between June 2016 and June 2019. Three RNA sequencing or microarray datasets of TB infection were used to identify the potential genes showing a common expression trend. The expression level of screened targets was determined by reverse transcription polymerase chain reaction and ELISA using samples of whole blood and peripheral blood mononuclear cells (PBMCs) isolated from 69 PTB patients and 69 healthy volunteers. The potential of the identified targets to predict the treatment outcomes was further studied. Results: Bioinformatics analysis demonstrated that a total of 91 genes were up-regulated in all the 3 datasets; among them, the expression of SLAMF8, LILRB4, and IL-10Ra was significantly increased at both the mRNA and protein levels in whole blood and PBMC samples of PTB patients compared with the healthy controls. The mortality rate increased significantly in SLAMF8 or LILRB4 high expression group compared with SLAMF8 or LILRB4 low expression group. Further, the decrease rate of bacteria in patients with SLAMF8 or LILRB4 high expression was slower than that in patients with SLAMF8 or LILRB4 low expression. Conclusion: This study provides a promising way to identify novel indicators for PTB. Moreover, the LILRB4 expression may play a role in predicting the outcome of treatments on PTB patients.
Comparative analysis of lung and blood transcriptomes in mice exposed to multi-walled carbon nanotubes
TOXICOLOGY AND APPLIED PHARMACOLOGY
Authors: Khaliullin, Timur O.; Yanamala, Naveena; Newman, Mackenzie S.; Kisin, Elena R.; Fatkhutdinova, Liliya M.; Shvedova, Anna A.
Abstract
Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) causes inflammation, fibroproliferation, immunotoxicity, and systemic responses in rodents. However, the search for representative biomarkers of exposure is an ongoing endeavor. Whole blood gene expression profiling is a promising new approach for the identification of novel disease biomarkers. We asked if the whole blood transcriptome reflects pathology-specific changes in lung gene expression caused by MWCNT. To answer this question, we performed mRNA sequencing analysis of the whole blood and lung in mice administered MWCNT or vehicle solution via pharyngeal aspiration and sacrificed 56 days later. The pattern of lung mRNA expression as determined using Ingenuity Pathway Analysis (IPA) was indicative of continued inflammation, immune cell trafficking, phagocytosis, and adaptive immune responses. Simultaneously, innate immunity-related transcripts (Plunc, Bpifb1, Reg3g) and cancer-related pathways were downregulated. IPA analysis of the differentially expressed genes in the whole blood suggested increased hematopoiesis, predicted activation of cancer/tumor development pathways, and atopy. There were several common upregulated genes between whole blood and lungs, important for adaptive immune responses: Cxcr1, Cd72, Sharpin, and Slc11a1. Trim24, important for T(H)2 cell effector function, was down regulated in both datasets. Hla-dqa1 mRNA was upregulated in the lungs and downregulated in the blood, as was Lilrb4, which controls the reactivity of immune response. "Cancer" disease category had opposing activation status in the two datasets, while the only commonality was "Hypersensitivity". Transcriptome changes occurring in the lungs did not produce a completely replicable pattern in whole blood; however, specific systemic responses may be shared between transcriptomic profiles.