Leveraging transcriptomics to develop bronchopulmonary dysplasia endotypes: a concept paper.

IMPACT: 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. INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Bioinformatic analyses can help identify BPD endotypes that associate with clinical definitions of BPD.

A clinical informatics approach to bronchopulmonary dysplasia: current barriers and future possibilities.

Bronchopulmonary dysplasia (BPD) is a complex, multifactorial lung disease affecting preterm neonates that can result in long-term pulmonary and non-pulmonary complications. Current therapies mainly focus on symptom management after the development of BPD, indicating a need for innovative approaches to predict and identify neonates who would benefit most from targeted or earlier interventions. Clinical informatics, a subfield of biomedical informatics, is transforming healthcare by integrating computational methods with patient data to improve patient outcomes. The application of clinical informatics to develop and enhance clinical therapies for BPD presents opportunities by leveraging electronic health record data, applying machine learning algorithms, and implementing clinical decision support systems. This review highlights the current barriers and the future potential of clinical informatics in identifying clinically relevant BPD phenotypes and developing clinical decision support tools to improve the management of extremely preterm neonates developing or with established BPD. However, the full potential of clinical informatics in advancing our understanding of BPD with the goal of improving patient outcomes cannot be achieved unless we address current challenges such as data collection, storage, privacy, and inherent data bias.