Table 1. Description of expected biomarker levels found in individuals using an understanding of disease dynamics in a system based on the more traditional (CANONICAL) framework and expanding that framework to include greater complexities and more ambiguous presentations (AMBIGUOUS).

Presentation	Antibody Titer	Clinical Disease	Pathogen Presence	Interpretation
CANONICAL
Unexposed/Susceptible (S)	Negative	Absent	No	Never exposed
Exposed (E)	Negative	Absent/Mild	Yes	Exposed, infected but not yet infectious
Infected/Infectious (I)	Positive	Severe	Yes	Recent infection, infectious
Past Exposure/Recovered (R)	Positive OR Negative	Absent	No	Recovered
AMBIGUOUS
a	High	Absent	Yes	Subclinical infection OR Delay in clinical manifestation relative to infection and immune response (antibody titer) OR Recent infection with rapid resolution of clinical disease
b	High	Absent	No	Recently cleared infection with resolution of clinical disease.
c	Very High	Absent	No	Re-exposure with boosting
d	Low to Medium	Moderate to Severe	No	Past (cleared) infection with residual antibodies and persistent clinical compromise despite clearance of pathogen. OR Past (cleared) infection with residual antibodies and disease from different etiology.
e	Absent	Moderate to Severe	No	As in d above, but with no residual antibodies.
f	Absent	Moderate to Severe	Yes	Clinical infection, but early stage so no detectable immune response (yet).
g	Low to Medium	Absent	Yes	Chronic subclinical infection. OR Early infection prior to maximum immune response. OR Individual heterogeneity in maximum immune response.
h	Absent	Absent	Yes	As in g above, but with no antibodies detected