Subtype-Aware Registration of Longitudinal Electronic Health Records
Abstract
Electronic Health Records (EHRs) contain extensive patient information that can inform downstream clinical decisions, such as mortality prediction, disease phenotyping, and disease onset prediction. A key challenge in EHR data analysis is the temporal gap between when a condition is first recorded and its actual onset time. Such timeline misalignment can lead to artificially distinct biomarker trends among patients with similar disease progression, undermining the reliability of downstream analyses and complicating tasks such as disease subtyping and outcome prediction. To address this challenge, we provide a subtype-aware timeline registration method that leverages data projection and discrete optimization to correct timeline misalignment. Through simulation and real-world data analyses, we demonstrate that the proposed method effectively aligns distorted observed records with the true disease progression patterns, enhancing subtyping clarity and improving performance in downstream clinical analyses. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work.
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Documentation timestamps reflect when events are recorded rather than when they occur, introducing systematic errors that can distort event sequencing, bias time-to-event analyses, and undermine model validity.
“Documentation timestamps are often used as surrogates for disease onset; however, they reflect when events are recorded rather than when they occur, introducing systematic errors that can distort event sequencing, bias time-to-event analyses, and undermine model validity9–12.”
From TimeX: Phenotype Onset Extraction from Clinical Narratives (2026) · cites this paper as [12]
Cites
Mining Electronic Health Records (EHRs): A Survey
Yadav, P., Steinbach, M., Kumar, V., & Simon, G. (2018) · ACM Computing Surveys · doi:10.1145/3127881 · Cited by 299 · see citing works
Song, X., Yu, A. S. L., Kellum, J. A., Waitman, L. R., Matheny, M. E., Simpson, S. Q., Hu, Y., & Liu, M. (2020) · Nature Communications · doi:10.1038/s41467-020-19551-w · Cited by 120 · see citing works
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TimeX: Phenotype Onset Extraction from Clinical Narratives
Chen, F., Jiang, S., Nguyen, Q. M., Ta, C. N., Wang, K., Chung, W. K., & Weng, C. (2026) · npj Health Systems · doi:10.1038/s44401-026-00099-8
Self-citation
- Authors
- Gai, X., Jiang, S., & Zhang, A. R.
- Affiliations
- Vanderbilt University (US)
- Duke University (US)
- Corresponding author
- Zhang, Anru R.
- Venue
- Journal of the American Statistical Association
- Publisher
- Informa UK Limited
- Published
- 2026-03-25
- Volume
- 121
- Issue
- 554
- Pages
- 917-928
- ISSN
- 0162-1459 (ISSN-L)
- 1537-274X
- OpenAlex
- W7123463902
- Cited by
- 0
- References
- 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Statistical Association (publishedVersion)
- Funders
- Division of Mathematical Sciences (CAREER-2203741)
- National Heart, Lung, and Blood Institute (R01HL168940)
- Topics
- Physical Sciences › Computer Science › Artificial Intelligence › Machine Learning in Healthcare
- Health Sciences › Health Professions › Health Information Management › Electronic Health Records Systems
- Health Sciences › Health Professions › Health Information Management › Medical Coding and Health Information
- Keywords
- electronic health records, disease subtyping, data projection, discrete optimization, disease progression, clinical outcome prediction
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