Department of Respiratory Medicine, Yancheng Hospital of Traditional Chinese Medicine; Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu, 224005, China.
Department of Gastroenterology, Jiangyin Hospital of Traditional Chinese Medicine; Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, Jiangsu, 214400, China.
BMC Pulm Med. 2024 Sep 17;24(1):458. doi: 10.1186/s12890-024-03249-6.
Idiopathic pulmonary fibrosis (IPF) is a severe lung condition, and finding better ways to diagnose and treat the disease is crucial for improving patient outcomes. Our study sought to develop an artificial neural network (ANN) model for IPF and determine the immune cell types that differed between the IPF and control groups.
From the Gene Expression Omnibus (GEO) database, we first obtained IPF microarray datasets. To conduct protein-protein interaction (PPI) networks and enrichment analyses, differentially expressed genes (DEGs) were screened between tissues of patients with IPF and tissues of controls. Afterward, we identified the important feature genes associated with IPF using random forest (RF) analysis, and then constructed and validated a prediction ANN mode. In addition, the proportions of immune cells were quantified using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) analysis, which was performed on microarray datasets based on gene expression profiling.
A total of 11 downregulated and 36 upregulated DEGs were identified. PPI networks and enrichment analyses were carried out; the immune system and extracellular matrix were the subjects of the enrichments. Using RF analysis, the significant feature genes LRRC17, COMP, ASPN, CRTAC1, POSTN, COL3A1, PEBP4, IL13RA2, and CA4 were identified. The nine feature gene scores were integrated into the ANN to develop a diagnostic prediction model. The receiver operating characteristic (ROC) curves demonstrated the strong diagnostic ability of the ANN in predicting IPF in the training and testing sets. An analysis of IPF tissues in comparison to normal tissues revealed a reduction in the infiltration of natural killer cells resting, monocytes, macrophages M0, and neutrophils; conversely, the infiltration of T cells CD4 memory resting, mast cells, and macrophages M0 increased.
LRRC17, COMP, ASPN, CRTAC1, POSTN, COL3A1, PEBP4, IL13RA2, and CA4 were determined as key feature genes for IPF. The nine feature genes in the ANN model will be extremely important for diagnosing IPF. It may be possible to use differentiated immune cells from IPF samples in comparison to normal samples as targets for immunotherapy in patients with IPF.
特发性肺纤维化(IPF)是一种严重的肺部疾病,寻找更好的诊断和治疗方法对于改善患者预后至关重要。我们的研究旨在开发用于 IPF 的人工神经网络(ANN)模型,并确定 IPF 组和对照组之间存在差异的免疫细胞类型。
我们首先从基因表达综合数据库(GEO)中获得 IPF 微阵列数据集。为了进行蛋白质-蛋白质相互作用(PPI)网络和富集分析,筛选了 IPF 患者组织与对照组组织之间的差异表达基因(DEGs)。之后,我们使用随机森林(RF)分析识别与 IPF 相关的重要特征基因,然后构建和验证预测 ANN 模型。此外,使用基于基因表达谱的微阵列数据集通过估计相对 RNA 转录物亚群(CIBERSORT)分析量化免疫细胞的比例。
共鉴定出 11 个下调和 36 个上调的 DEGs。进行了 PPI 网络和富集分析;免疫系统和细胞外基质是富集的主题。使用 RF 分析,鉴定出重要特征基因 LRRC17、COMP、ASPN、CRTAC1、POSTN、COL3A1、PEBP4、IL13RA2 和 CA4。将这 9 个特征基因评分整合到 ANN 中,以开发诊断预测模型。训练集和测试集的接收者操作特征(ROC)曲线表明 ANN 具有很强的预测 IPF 的能力。与正常组织相比,对 IPF 组织的分析表明,自然杀伤细胞静息、单核细胞、巨噬细胞 M0 和中性粒细胞浸润减少;相反,T 细胞 CD4 记忆静息、肥大细胞和巨噬细胞 M0 浸润增加。
LRRC17、COMP、ASPN、CRTAC1、POSTN、COL3A1、PEBP4、IL13RA2 和 CA4 被确定为 IPF 的关键特征基因。ANN 模型中的 9 个特征基因对于诊断 IPF 将非常重要。与正常样本相比,从 IPF 样本中区分免疫细胞可能成为 IPF 患者免疫治疗的靶点。