Sparse Machine Learning Pipeline with Stabl Identifies Cord Blood Multi-Omic Signatures of Bronchopulmonary Dysplasia

Background

Several omics studies have been completed in recent years, with the goal of identifying biomarkers of complex multifactorial diseases, such as bronchopulmonary dysplasia (BPD).

Objective

To evaluate the performance of 3 distinct omics platforms, using a machine learning pipeline with integration of sparse, reliable and adaptive biomarker identification (Stabl).

Methods

Using a well-characterized birth cohort, cord blood metabolomics, proteomics and adductomics data were integrated with Least Absolute Shrinkage and Selection Operator (LASSO) regression and Stabl, to evaluate predictive performance for BPD.

Results

Sparse multivariable modeling of 45,000 features measured in 217 infants (52 term, 165 extremely preterm ≤28 weeks; 82 with BPD and 35 with severe BPD/death) identified a perfect signature for preterm birth with both LASSO and Stabl (AUROC=1.0; p<0.001). Analysis of the preterm group yielded excellent predictive power for severe BPD (AUROC=0.83; p=0.005). Stabl identified a set of 12 biomarkers (2 adducts, 3 proteins and 7 metabolites) with good performance for predicting grade III BPD (AUROC=0.76; P=0.03). Biomarkers across the 3 omics platforms revealed dysregulated pathways of innate/adaptive immune responses, metabolic programming and oxidative stress.

Conclusions

The sparse machine learning pipeline is a complementary approach for identifying novel pathways and biomarkers of multifactorial BPD and its endotypes.

Impact Statement

• Cord blood multi-omics provides a snapshot at birth of the complex interplay between the perinatal metabolome, proteome and exposome.

• We leveraged novel machine learning approaches including integration of sparse, reliable and adaptive biomarker identification (Stabl) to identify novel cord blood biomarkers that elucidate perinatal pathways of BPD, mediated by preterm birth.

• Biomarkers across 3 omics platforms revealed dysregulated pathways of innate/adaptive immune responses, metabolic programming and oxidative stress.

• The sparse machine learning pipeline is a complementary approach for identifying novel biomarkers of multifactorial BPD and its endotypes.