A framework for employing longitudinally collected multicenter electronic health records to stratify heterogeneous patient populations on disease history. (9th February 2022)

• Record Type: Journal Article
• Authors: Maurits, Marc P; Korsunsky, Ilya; Raychaudhuri, Soumya; Murphy, Shawn N; Smoller, Jordan W; Weiss, Scott T; Petukhova, Lynn M; Weng, Chunhua; Wei, Wei-Qi; Huizinga, Thomas W J; Reinders, Marcel J T; Karlson, Elizabeth W; van den Akker, Erik B; Knevel, Rachel
• Is Part Of: Journal of the American Medical Informatics Association. Volume 29:Number 5(2022)
• Page Start: 761
• Page End: 769
• Publication Date: 2022-02-09
• Subjects: electronic health records -- clustering -- electronic medical records -- ICD -- PhenoGraph -- eMERGE; Medical informatics -- Periodicals; Information Services -- Periodicals; Medical Informatics -- Periodicals; Médecine -- Informatique -- Périodiques; Informatica; Geneeskunde; Informatique médicale; Computer network resources; Electronic journals; 610.285
• DOI: 10.1093/jamia/ocac008
• Languages: English
• ISSNs: 1067-5027

Abstract

Abstract: Objective: To facilitate patient disease subset and risk factor identification by constructing a pipeline which is generalizable, provides easily interpretable results, and allows replication by overcoming electronic health records (EHRs) batch effects. Material and Methods: We used 1872 billing codes in EHRs of 102 880 patients from 12 healthcare systems. Using tools borrowed from single-cell omics, we mitigated center-specific batch effects and performed clustering to identify patients with highly similar medical history patterns across the various centers. Our visualization method (PheSpec) depicts the phenotypic profile of clusters, applies a novel filtering of noninformative codes (Ranked Scope Pervasion), and indicates the most distinguishing features. Results: We observed 114 clinically meaningful profiles, for example, linking prostate hyperplasia with cancer and diabetes with cardiovascular problems and grouping pediatric developmental disorders. Our framework identified disease subsets, exemplified by 6 "other headache" clusters, where phenotypic profiles suggested different underlying mechanisms: migraine, convulsion, injury, eye problems, joint pain, and pituitary gland disorders. Phenotypic patterns replicated well, with high correlations of ≥0.75 to an average of 6 (2–8) of the 12 different cohorts, demonstrating the consistency with which our method discovers disease history profiles. Discussion: Costly clinical research ventures should be based on solid hypotheses. We repurpose methods from single-cell omics to build these hypotheses from observational EHR data, distilling useful information from complex data. Conclusion: We establish a generalizable pipeline for the identification and replication of clinically meaningful (sub)phenotypes from widely available high-dimensional billing codes. This approach overcomes datatype problems and produces comprehensive visualizations of validation-ready phenotypes.