间质性肺病的转录组学:系统综述和荟萃分析。

IF 16.6 1区 医学 Q1 RESPIRATORY SYSTEM
Daniel He, Sabina A Guler, Casey P Shannon, Christopher J Ryerson, Scott J Tebbutt
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引用次数: 0

摘要

目的:基因表达(转录组学)研究揭示了间质性肺病(ILD)的潜在机制:基因表达(转录组学)研究揭示了间质性肺病(ILD)的潜在机制,但研究的样本量往往有限,亚型间的比较也很少。本研究旨在确定和验证 ILD 亚型的共识转录组特征:我们采用单个参与者数据的方法对纤维化 ILD 转录组学研究进行了系统性回顾和荟萃分析,并纳入了对人类成人 ILD 样本的批量转录组学研究,但排除了那些关注单个细胞群的研究。从43项研究中提取了患者水平的数据和表达矩阵,并使用多变量综合算法对其进行整合,以建立ILD分类模型:利用 24 项研究的 1459 份样本,我们确定了特发性肺纤维化(IPF)、超敏性肺炎(HP)、特发性非特异性间质性肺炎(NSIP)和系统性硬化症相关 ILD(SSc-ILD)与对照样本的转录组特征,并在 8 项研究的 308 份样本上进行了验证(接收者操作曲线下面积 [AUC]=0.99[95%CI:0.99-1.00],HP AUC=0.91 [0.84-0.99],NSIP AUC=0.94 [0.88-0.99],SSc-ILD AUC=0.98 [0.93-1.00])。值得注意的是,荟萃分析首次发现了强大的肺转录组学特征,可将 IPF(AUC=0.71 [0.63-0.79])和 HP(AUC=0.76 [0.63-0.89])与其他纤维化 ILD 区分开来,无监督学习算法发现了与强迫生命容量(FVC)和一氧化碳肺弥散容量(DLCO)预测百分比下降相关的 ILD 潜在分子内型。转录组学特征反映了细胞特异性和疾病特异性基因表达的变化:我们对纤维化 ILD 转录组学进行了迄今为止首次系统回顾和最大规模的荟萃分析,确定了具有临床意义的可重复转录组特征。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transcriptomics of interstitial lung disease: a systematic review and meta-analysis.

Objective: Gene expression (transcriptomics) studies have revealed potential mechanisms of interstitial lung disease (ILD), yet sample sizes of studies are often limited and between-subtype comparisons are scarce. The aim of this study was to identify and validate consensus transcriptomic signatures of ILD subtypes.

Methods: We performed a systematic review and meta-analysis of fibrotic ILD transcriptomics studies using an individual participant data approach, and included studies examining bulk transcriptomics of human adult ILD samples and excluding those focusing on individual cell populations. Patient-level data and expression matrices were extracted from 43 studies and integrated using a multivariable integrative algorithm to develop ILD classification models.

Results: Using 1459 samples from 24 studies, we identified transcriptomic signatures for idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), idiopathic nonspecific interstitial pneumonia (NSIP), and systemic sclerosis-associated ILD (SSc-ILD) against control samples, which were validated on 308 samples from 8 studies (area under receiver operating curve [AUC]=0.99 [95% CI: 0.99-1.00], HP AUC=0.91 [0.84-0.99], NSIP AUC=0.94 [0.88-0.99], SSc-ILD AUC=0.98 [0.93-1.00]). Significantly, meta-analysis allowed, for the first time, identification of robust lung transcriptomics signatures to discriminate IPF (AUC=0.71 [0.63-0.79]) and HP (AUC=0.76 [0.63-0.89]) from other fibrotic ILDs, and unsupervised learning algorithms identified putative molecular endotypes of ILD associated with decreased forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted. Transcriptomics signatures were reflective of both cell-specific and disease-specific changes in gene expression.

Conclusion: We present the first systematic review and largest meta-analysis of fibrotic ILD transcriptomics to date, identifying reproducible transcriptomic signatures with clinical relevance.

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来源期刊
European Respiratory Journal
European Respiratory Journal 医学-呼吸系统
CiteScore
27.50
自引率
3.30%
发文量
345
审稿时长
2-4 weeks
期刊介绍: The European Respiratory Journal (ERJ) is the flagship journal of the European Respiratory Society. It has a current impact factor of 24.9. The journal covers various aspects of adult and paediatric respiratory medicine, including cell biology, epidemiology, immunology, oncology, pathophysiology, imaging, occupational medicine, intensive care, sleep medicine, and thoracic surgery. In addition to original research material, the ERJ publishes editorial commentaries, reviews, short research letters, and correspondence to the editor. The articles are published continuously and collected into 12 monthly issues in two volumes per year.
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