ABSTRACTObjectiveHigh-throughput electronic phenotyping algorithms can accelerate translational research using data from electronic health record (EHR) systems. The temporal information buried in EHRs are often underutilized in developing computational phenotypic definitions. The objective of this study is to develop a high-throughput phenotyping method, leveraging temporal sequential patterns of discrete events from electronic health records.Materials and MethodsWe develop a representation mining algorithm to extract five classes of representations from EHR diagnosis and medication records: the aggregated vector of the records (AVR), the traditional immediate sequential patterns (SPM), the transitive sequential patterns (tSPM), as well as two hybrid classes of SPM+AVR and tSPM+AVR. A final small set of representations were selected from each class using the MSMR dimensionality reduction algorithm. Using EHR data on 10 phenotypes from Mass General Brigham Biobank, we trained regularized logistic regression algorithms, which we validated using labeled data.ResultsPhenotyping with temporal sequences resulted in a superior classification performance across all 10 phenotypes compared with the AVR representations that are conventionally used in electronic phenotyping. Although this study only utilizes the diagnosis and medication records, the high-throughput algorithm’s classification performance was superior or similar to the performance of previously published electronic phenotyping algorithms. We characterize and evaluate the top transitive sequences of diagnosis records paired with the records of risk factors, symptoms, complications, medications, or vaccinations.DiscussionThe proposed high-throughput phenotyping approach enables seamless discovery of sequential record combinations that may be difficult to assume from raw EHR data. A transitive sequence can offer a more accurate characterization of the phenotype, compared with its individual components. Additionally, the identified transitive sequences of a given phenotype reflect the actual lived experiences of the patients with that particular disease.ConclusionSequential data representations provide a precise mechanism for incorporating raw EHR records into downstream Machine Learning.