The Molecular Human – A Roadmap of Molecular Interactions Linking Multiomics Networks with Disease Endpoints

Abstract

AbstractIn-depth multiomics phenotyping can provide a molecular understanding of complex physiological processes and their pathologies. Here, we report on the application of 18 diverse deep molecular phenotyping (omics-) technologies to urine, blood, and saliva samples from 391 participants of the multiethnic diabetes study QMDiab. We integrated quantitative readouts of 6,304 molecular traits with 1,221,345 genetic variants, methylation at 470,837 DNA CpG sites, and gene expression of 57,000 transcripts using between-platform mutual best correlations, within-platform partial correlations, and genome-, epigenome-, transcriptome-, and phenome-wide associations. The achieved molecular network covers over 34,000 statistically significant trait-trait links and illustrates “The Molecular Human”. We describe the variances explained by each omics layer in the phenotypes age, sex, BMI, and diabetes state, platform complementarity, and the inherent correlation structures of multiomics. Finally, we discuss biological aspects of the networks relevant to the molecular basis of complex disorders. We developed a web-based interface to “The Molecular Human”, which is freely accessible athttp://comics.metabolomix.comand allows dynamic interaction with the data.