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A transcriptomics-based meta-analysis identifies a cross-tissue signature for sarcoidosis

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单位: [1]China Japan Friendship Hosp, Dept Pulm & Crit Care Med, Beijing, Peoples R China [2]Chinese Acad Med Sci Peking Union Med Coll, Clin Trial Ctr, Canc Hosp, Natl Canc Ctr,Natl Clin Res Ctr Canc, Beijing, Peoples R China [3]Tsinghua Univ, Sch Med, Beijing, Peoples R China [4]Chinese Acad Med Sci, Inst Resp Med, Natl Ctr Resp Med, Natl Clin Res Ctr Resp Dis, Beijing, Peoples R China [5]Univ Hosp, Ruhrlandklin, Ctr Interstitial & Rare Lung Dis, Dept Pneumol, Essen, Germany [6]Peking Univ Joint Ctr Life Sci, Tsinghua Univ, Beijing, Peoples R China [7]Peking Union Med Coll, Beijing, Peoples R China
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关键词: sarcoidosis transcriptome interferon IL-17 machine learning

摘要:
Sarcoidosis is a granulomatous disease of unknown etiology, immunologically characterized by a Th1 immune response. Transcriptome-wide expression studies in various types of sarcoid tissues contributed to better understanding of disease mechanisms. We performed a systematic database search on Gene Expression Omnibus (GEO) and utilized transcriptomic data from blood and sarcoidosis-affected tissues in a meta-analysis to identify a cross-tissue, cross-platform signature. Datasets were further separated into training and testing sets for development of a diagnostic classifier for sarcoidosis. A total of 690 differentially expressed genes were identified in the analysis among various tissues. 29 of the genes were robustly associated with sarcoidosis in the meta-analysis both in blood and in lung-associated tissues. Top genes included LINC01278 (P = 3.11 x 10(-13)), GBP5 (P = 5.56 x 10(-07)), and PSMB9 (P = 1.11 x 10(-06)). Pathway enrichment analysis revealed activated IFN-gamma, IL-1, and IL-18, autophagy, and viral infection response. IL-17 was observed to be enriched in peripheral blood specific signature genes. A 16-gene classifier achieved excellent performance in the independent validation data (AUC 0.711-0.964). This study provides a cross-tissue meta-analysis for expression profiles of sarcoidosis and identifies a diagnostic classifier that potentially can complement more invasive procedures.

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出版当年[2021]版:
大类 | 3 区 医学
小类 | 2 区 医学:内科
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 医学:内科
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出版当年[2020]版:
Q1 MEDICINE, GENERAL & INTERNAL
最新[2023]版:
Q1 MEDICINE, GENERAL & INTERNAL

影响因子: 最新[2023版] 最新五年平均[2021-2025] 出版当年[2020版] 出版当年五年平均[2016-2020] 出版前一年[2019版] 出版后一年[2021版]

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第一作者单位: [1]China Japan Friendship Hosp, Dept Pulm & Crit Care Med, Beijing, Peoples R China [2]Chinese Acad Med Sci Peking Union Med Coll, Clin Trial Ctr, Canc Hosp, Natl Canc Ctr,Natl Clin Res Ctr Canc, Beijing, Peoples R China [3]Tsinghua Univ, Sch Med, Beijing, Peoples R China
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通讯机构: [1]China Japan Friendship Hosp, Dept Pulm & Crit Care Med, Beijing, Peoples R China [4]Chinese Acad Med Sci, Inst Resp Med, Natl Ctr Resp Med, Natl Clin Res Ctr Resp Dis, Beijing, Peoples R China [6]Peking Univ Joint Ctr Life Sci, Tsinghua Univ, Beijing, Peoples R China [7]Peking Union Med Coll, Beijing, Peoples R China
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