Global patterns of prognostic biomarkers across disease space

Abstract

There is a multitude of pathological conditions that affect human health, yet we currently lack a predictive model for most diseases, and underlying mechanisms that are shared by multiple diseases are poorly understood. We leveraged baseline clinical biomarker data and long-term disease outcomes in UK Biobank to build prognostic multivariate survival models for over 200 most common diseases. We construct a similarity map between biomarker-disease hazard ratios and demonstrate broad patterns of shared similarity in biomarker profiles across the entire disease space. Further aggregation of risk profiles through density based clustering showed that biomarker-risk profiles can be partitioned into few distinct clusters with characteristic patterns representative of broad disease categories. To confirm these risk patterns we built disease co-occurrence networks in the UK Biobank and US HCUP hospitalization databases, and compared similarity in biomarker risk profiles to disease co-occurrence. We show that proximity in the biomarker-disease space is strongly related to the occurrence of disease comorbidity, suggesting biomarker profile patterns can be used for both predicting future outcomes as well as a sensitive mechanism for detecting under-diagnosed disease states.