A Composite Biomarker Signature of Type 1 Diabetes Risk Identified via Augmentation of Parallel Multi-Omics Data from a Small Cohort

Abstract

ABSTRACTBackgroundBiomarkers of early pathogenesis of type 1 diabetes (T1D) are crucial to enable effective prevention measures in at-risk populations before significant damage occurs to their insulin producing beta-cell mass. We recently introduced the concept of integrated parallel multi-omics and employed a novel data augmentation approach which identified promising candidate biomarkers from a small cohort of high-risk T1D subjects. We now validate selected biomarkers to generate a potential composite signature of T1D riskMethodsTwelve candidate biomarkers, which were identified in the augmented data and selected based on their fold-change relative to healthy controls and cross-reference to proteomics data previously obtained in the expansive TEDDY and DAISY cohorts, were measured in the original samples by ELISAResultsAll 12 biomarkers had established connections with lipid/lipoprotein metabolism, immune function, inflammation, and diabetes, but only 7 were found to be markedly changed in the high-risk subjects compared to the healthy controls: ApoC1 and PON1 were reduced while CETP, CD36, FGFR1, IGHM, PCSK9, SOD1, and VCAM1 were elevatedConclusionsResults further highlight the promise of our data augmentation approach in unmasking important patterns and pathologically significant features in parallel multi-omics datasets obtained from small sample cohorts to facilitate the identification of promising candidate T1D biomarkers for downstream validation. They also support the potential utility of a composite biomarker signature of T1D risk characterized by the changes in the above markers.