Department of Pediatrics, Division of Neonatology, University of Texas Health San Antonio, San Antonio, TX, USA.
Division of Neonatology, Dayton Children's Hospital, Cincinnati, OH, USA.
Respir Res. 2023 Nov 15;24(1):284. doi: 10.1186/s12931-023-02596-y.
Bronchopulmonary dysplasia has multiple definitions that are currently based on phenotypic characteristics. Using an unsupervised machine learning approach, we created BPD subclasses (e.g., endotypes) by clustering whole microarray data. T helper 17 cell differentiation was the most significant pathway differentiating the BPD endotypes.
Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. Discovery of BPD endotypes in an unbiased format, derived from the peripheral blood transcriptome, may uncover patterns underpinning this complex lung disease.
An unsupervised agglomerative hierarchical clustering approach applied to genome-wide expression of profiling from 62 children at day of life five was used to identify BPD endotypes. To identify which genes were differentially expressed across the BPD endotypes, we formulated a linear model based on least-squares minimization with empirical Bayes statistics.
Four BPD endotypes (A, B,C,D) were identified using 7,319 differentially expressed genes. Across BPD endotypes, 5,850 genes had a p value < 0.05 after multiple comparison testing. Endotype A consisted of neonates with a higher gestational age and birthweight. Endotypes B-D included neonates between 25 and 26 weeks and a birthweight range of 640 to 940 g. Endotype D appeared to have a protective role against BPD compared to Endotypes B and C (36% vs. 62% vs. 60%, respectively). The most significant pathway focused on T helper 17 cell differentiation.
Bioinformatic analyses can help identify BPD endotypes that associate with clinical definitions of BPD.
支气管肺发育不良（BPD）有多种定义，目前基于表型特征。我们使用无监督机器学习方法，通过聚类全基因组芯片数据创建了 BPD 亚型（例如，内型）。辅助性 T 细胞 17 细胞分化是区分 BPD 内型的最重要途径。
支气管肺发育不良（BPD）是极早产儿最常见的并发症。在无偏置格式中发现 BPD 内型，源自外周血转录组，可能揭示这种复杂肺部疾病的潜在模式。
应用于 62 名婴儿出生后第 5 天全基因组表达谱的无监督凝聚层次聚类方法用于识别 BPD 内型。为了确定哪些基因在 BPD 内型之间存在差异表达，我们基于最小二乘法和经验贝叶斯统计制定了线性模型。
使用 7319 个差异表达基因识别出 4 个 BPD 内型（A、B、C、D）。在 BPD 内型之间，经过多次比较测试后，有 5850 个基因的 p 值<0.05。内型 A 由胎龄和出生体重较高的新生儿组成。内型 B-D 包括胎龄在 25 至 26 周之间、出生体重在 640 至 940 克之间的新生儿。与内型 B 和 C 相比，内型 D 似乎对 BPD 具有保护作用（分别为 36%、62%和 60%）。最重要的途径集中在辅助性 T 细胞 17 细胞分化。
生物信息学分析可以帮助识别与 BPD 临床定义相关的 BPD 内型。
