OnPLS-based multi-block data integration: a multivariate approach to interrogating biological interactions in asthma.
Reinke SN., Galindo-Prieto B., Skotare T., Broadhurst DI., Singhania A., Horowitz D., Djukanovic R., Hinks TSC., Geladi P., Trygg J., Wheelock CE.
Integration of multi-omics data remains a key challenge in fulfilling the potential of comprehensive systems biology. Multiple-block orthogonal projections to latent structures (OnPLS) is a projection method that simultaneously models multiple data matrices, reducing feature space without relying on a priori biological knowledge. In order to improve the interpretability of OnPLS models, the associated multi-block variable influence on orthogonal projections (MB-VIOP) method is used to identify variables with the highest contribution to the model. This study combined OnPLS and MB-VIOP with interactive visualisation methods to interrogate an exemplar multi-omics study, using a subset of 22 individuals from an asthma cohort. Joint data structure in six data blocks was assessed: transcriptomics; metabolomics; targeted assays for sphingolipids, oxylipins, and fatty acids; and a clinical block including lung function, immune cell differentials, and cytokines. The model identified 7 components, 2 of which had contributions from all blocks (globally joint structure), and 5 that had contributions from 2-5 blocks (locally joint structure). Components 1 and 2 were the most informative, identifying differences between healthy controls and asthmatics, and a disease-sex interaction, respectively. The interactions between features selected by MB-VIOP were visualised using chord plots, yielding putative novel insights into asthma disease pathogenesis, the effects of asthma treatment, and biological roles of uncharacterised genes. For example, the gene ATP6V1G1, which has been implicated in osteoporosis, correlated with metabolites that are dysregulated by inhaled corticoid steroids (ICS), providing insight into the mechanisms underlying bone density loss in asthma patients taking ICS. These results show the potential for OnPLS, combined with MB-VIOP variable selection and interaction visualisation techniques, to generate hypotheses from multi-omics studies and inform biology.