Table 2.
Sensitivity and Specificity Comparison Between 2-tier Serology and the Metabolomics LASSO Statistical Model
| No. of Samples Tested by Serologya | WCS EIA-VIDAS Results |
C6 EIA Results |
Immunoblot Resultsb (Marblot) % Pos. |
2-Tier Testing (VIDAS/Marblot)b |
2-Tier Testing (C6/Marblot)b |
Alternative 2-Tier Testing (VIDAS/C6)b |
Metabolomics LASSO Model |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| % Pos. | % Pos. | IgM | IgG | IgM and IgG | No. Pos. Tests | Se. % | Sp. % | No. Pos. Tests | Se. % | Sp. % | No. Pos. Tests | Se. % | Sp. % | No. of Samples Testedc | No. Pos. Tests | Se. % | Sp. % | ||
| Training-Set | |||||||||||||||||||
| Subjects with early Lyme disease | |||||||||||||||||||
| Early Lyme | 89 | 58 | 52 | 30 | 3 | 9 | 33 | 37 | … | 31 | 35 | … | 37 | 42 | … | 158 | 156 | 99d | … |
| Non-Lyme disease controls | |||||||||||||||||||
| Healthy controls | 50 | 6 | 4 | 2 | 0 | 0 | 0 | … | 100 | 1 | … | 98 | 0 | … | 100 | 140 | 1 | … | 99e |
| Test-Set | |||||||||||||||||||
| Subjects with early Lyme disease | |||||||||||||||||||
| Early Lyme | 91 | 64 | 60 | 36 | 4 | 8 | 40 | 44 | … | 39 | 43 | … | 44 | 48 | … | 369 | 324 | 88d | … |
| C6-positive | 22 | 68 | 100 | 27 | 5 | 9 | 9 | 41 | … | 9 | 41 | … | 15 | 68 | … | 22 | 19 | 86f | … |
| Non-Lyme disease controls | |||||||||||||||||||
| Healthy controls | 108 | 10 | 0g | 4 | 0 | 0 | 0 | … | 100 | 0g | … | 100 | 0g | … | 100 | 187 | 10 | … | 95h |
| Other Diseases | 101 | 33 | 6 | 8 | 0 | 0 | 5 | … | 95 | 2 | … | 98 | 4 | … | 96 | 101 | 6 | … | 94i |
Abbreviations: CDC, Centers for Disease Control and Prevention; EIA, enzyme immunoassay; IgG, immunoglobulin G; IgM, immunoglobulin M; LC-MS, liquid chromatography-mass spectrometry; No., number; Pos., positive; Se., sensitivity; Sp., specificity; WCS, whole cell sonicate.
a Each sample was only tested one time.
b CDC 2-tier interpretation criteria were used [4]; however, all samples were tested by IgM immunoblots regardless of duration of illness.
c The serum samples tested included replicates due to multiple LC-MS runs.
d The sensitivity of LASSO modeling was significantly greater (P < .0001) than WCS EIA-VIDAS, C6 EIA, or 2-tier testing (VIDAS/Marblot). Statistical testing was not performed with the other 2-tier methods.
e The specificity of LASSO modeling was significantly greater (P < .003) than WCS EIA-VIDAS and not significantly different from C6 EIA (P = .06) or 2-tier testing (VIDAS/Marblot) (P = 1.00). Statistical testing was not performed with the other 2-tier methods.
f Sample size was not large enough to establish statistical significance for sensitivity.
g Healthy controls that were C6-positive were excluded from the test-set.
h The specificity of LASSO modeling did not differ significantly from WCS EIA-VIDAS (P = .14), C6 EIA (P = .08), or 2-tier testing (VIDAS/Marblot) (P = 1.00). Statistical testing was not performed with the other 2-tier methods.
i The specificity of LASSO modeling did not differ significantly from C6 EIA (P = 1.00) or 2-tier testing (VIDAS/Marblot) (P = .76), but was significantly better than the WCS EIA-VIDAS (P = .001). Statistical testing was not performed with the other 2-tier methods.