Learning and Mapping Lyme Disease Patient Trajectories from Electronic Medical Data for Stratification of Disease Risk and Therapeutic Response

Abstract

ABSTRACTBackgroundLyme disease (LD) is an epidemic, tick-borne illness with approximately 329,000 incidences diagnosed each year in United States. Long-term use of antibiotics is associated with serious complications, including post-treatment Lyme disease syndrome (PTLDS). The landscape of comorbidities and health trajectories associated with LD and associated treatments is not fully understood. Consequently, there is an urgent need to improve clinical management of LD based on a more precise understanding of disease and patient stratification.MethodsWe used a precision medicine machine-learning approach based on high-dimensional electronic medical records (EMRs) to characterize the heterogeneous comorbidities in a LD population and develop systematic predictive models for identifying medications that influence the risk of subsequent comorbidities.FindingsWe identified 3, 16, and 17 comorbidities at broad disease categories associated with LD within 2, 5, and 10 years of diagnosis, respectively. At higher resolution of ICD-9 levels, we pinpointed specific co-morbid diseases on a timescale that matched the symptoms associated with PTLDS. We identified 7, 30, and 35 medications that influenced the risks of the reported comorbidities within 2, 5, and 10 years, respectively. These medications included six previously associated with the identified comorbidities and 29 new findings. For instance, the first-line antibiotic doxycycline exhibited a consistently protective effect for typical symptoms of LD, including ‘backache Not Otherwise Specified (NOS)’ and ‘chronic rhinitis’, but consistently increased the risk of ‘cataract NOS’, ‘tear film insufficiency NOS’, and ‘nocturia’.InterpretationOur approach and findings suggest new hypotheses for precision medicine treatments regimens and drug repurposing opportunities tailored to the phenotypic profiles of LD patients.FundingThe Steven & Alexandra Cohen Foundation