In Journal of pathology informatics ; h5-index 23.0
Diagnostic advances have not kept pace with the expansion of Lyme disease caused by Borrelia burgdorferi and transmitted by ticks. Lyme disease clinical manifestations can overlap with many other diagnoses making Lyme disease a critical part of many differential diagnoses in endemic areas. Current diagnostic blood tests rely on a 2-tiered algorithm for which the second step is either a time-consuming western blot or a whole cell lysate immunoassay. Neither of these second step tests allow for rapid results of this critical rule out test. We hypothesized that using western blot confirmation information, we could create computational models to propose recombinant second-tier tests that would allow for more rapid, automated, and specific testing algorithms. We propose here a framework for assessing retrospective data to determine putative recombinant assay components. A retrospective pediatric cohort of 2755 samples submitted for Lyme disease screening was assessed using support vector machine learning algorithms to optimize tier 1 diagnostic thresholds for the Vidas IgG II assay and determine optimal tier 2 components for both a positive and negative confirmation test. In cases where the tier 1 screen was negative, but clinical suspicion was high, we found that 1 protein (L58) could be used to reduce false-negative results. For second-tier testing of screen positive cases, we found that 6 proteins could be used to reduce false-positive results (L18, L39M, L39, L41, L45, and L58) with a final machine learning classifier or 2 proteins using a final rules-based approach (L41, L18). This led to an overall accuracy of 92.36% for the proposed algorithm without a final machine learning classifier and 92.12% with integration of the machine learning classifier in the final algorithm when compared to the IgG western blot as the gold-standard. Use of this framework across multiple assays and institutions will allow for a data-driven approach to assay development to provide laboratories and patients with the improvements in turnaround time needed for this testing.
Elkhadrawi Mahmoud, Lopez-Nunez Oscar, Akcakaya Murat, Wheeler Sarah E
2023
2-tier algorithm, Lyme, Sequential feature selection, Serology, Support Vector Machines (SVM)
