Comprehensive identification of immuno-related transcriptional signature for active pulmonary tuberculosis by integrated analysis of array and single cell RNA-seq
Comprehensive identification of immuno-related transcriptional signature for active pulmonary tuberculosis by integrated analysis of array and single cell RNA-seq
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通过芯片和单细胞 RNA-seq 的综合分析全面鉴定活动性肺结核的免疫相关转录特征
DOI：
10.1016/j.jinf.2022.08.017
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发表时间：
2022-10-13
影响因子：
28.2
通讯作者：
Zhu, Jialou
中科院分区：
文献类型：
--
作者：
Xu, Yuzhong;Tan, Yaoju;Zhu, Jialou
背景：结核病（TB）仍然是全世界发病和死亡的主要原因。然而，人类感染结核分枝杆菌（Mtb）后免疫反应的分子机制仍不清楚。在全基因组范围内评估健康和疾病之间血液中转录本丰度的变化，可以全面了解结核分枝杆菌感染对宿主防御的影响，并提供识别新型结核病生物标志物的可靠方法。方法：我们通过 10X Genomics 平台将阵列表达谱和单细胞 RNA 测序 (scRNA-seq) 相结合，以更好地说明结核病的免疫相关转录特征，并探索区分结核病和潜伏结核病感染的潜在诊断标志物(LTBI) 和健康对照 (HC)。研究结果：基于差异表达基因 (DEG) 的通路分析表明，免疫转录谱可以有效区分 TB、LTBI 和 HC。经过基于DEG的WGCNA和PPI网络分析，我们筛选出与结核病高度相关的三个关键免疫相关中枢基因（ADM、IFIT3和SERPING1）。进一步验证发现，在成人和儿童数据集中，只有 ADM 表达在结核病患者中显着增加。通过比较 TB、LTBI 和 HC 的 scRNA-seq 数据集，我们观察到 TB 髓细胞中 ADM 的表达水平和比例显着升高，进一步支持 ADM 表达变化可以区分 TB 患者与 LTBI 和 HC。此外，hsa-miR-24-3p-NEAT1-ADM-CEBPB调控途径可能是调控结核病发病机制的关键网络之一。尽管需要在更大的队列中进行进一步研究，但我们提供了有用且新颖的见解来探索结核病诊断和干预的潜在候选基因。解释：我们建议外周血中 ADM 的表达可以作为区分 TB 与 LTBI 和 HC 的新型生物标志物。(c) 2022 作者。由爱思唯尔有限公司代表英国感染协会出版。这是一篇基于 CC BY-NC-ND 许可证的开放获取文章 (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Background: Tuberculosis (TB) continues to be a major cause of morbidity and mortality worldwide. How-ever, the molecular mechanism underlying immune response to human infection with Mycobacterium tuberculosis (Mtb) remains unclear. Assessing changes in transcript abundance in blood between health and disease on a genome-wide scale affords a comprehensive view of the impact of Mtb infection on the host defense and a reliable way to identify novel TB biomarkers.Methods: We combined expression profiling by array and single cell RNA-sequencing (scRNA-seq) via 10X Genomics platform to better illustrate the immuno-related transcriptional signature of TB and explore potential diagnostic markers for differentiating TB from latent tuberculosis infection (LTBI) and healthy control (HC). Findings: Pathway analysis based on differential expressed genes (DEGs) revealed that immune transcrip-tional profiling could effectively differ TB with LTBI and HC. Following WGCNA and PPI network analysis based on DEGs, we screened out three key immuno-related hub genes (ADM, IFIT3 and SERPING1) highly associated with TB. Further validation found only ADM expression significantly increased in TB patients in both adult and children's datasets. By comparing the scRNA-seq datasets from TB, LTBI and HC, we observed a remarkable elevated expression level and proportion of ADM in TB Myeloid cells, further sup-porting that ADM expression changes could distinguish patients with TB from LTBI and HC. Besides, the hsa-miR-24-3p-NEAT1-ADM-CEBPB regulation pathway might be one of the critical networks regulating the pathogenesis of TB. Although further investigation in a larger cohort is warranted, we provide useful and novel insight to explore the potential candidate genes for TB diagnosis and intervention. Interpretation: We propose that the expression of ADM in peripheral blood could be used as a novel biomarker for differentiating TB with LTBI and HC.(c) 2022 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )