Codename: HAL-QuIC
An R project for the kinetic modeling of the RT-QuIC assay
What is RT-QuIC?
Real-Time Quaking-Induced Conversion (RT-QuIC) is a highly sensitive assay used to detect misfolded prion proteins. A small amount of seed material — typically brain or lymph node homogenate — is incubated with a recombinant substrate prion protein under semi-continuous agitation. When prion seeds are present, they template the misfolding of the substrate, forming amyloid aggregates. These aggregates are measured in real time via thioflavin T (ThT) fluorescence, producing a characteristic sigmoidal growth curve.
RT-QuIC kinetics
RT-QuIC has been validated repeatedly for its ability to detect prions, however, the shape of the curve may offer further insight into the characteristics of the original prion seed as well as the mechanism of the prion-substrate interaction. It is well-known that generally, higher concentrations of initial seed material lead to a faster reaction, but the overall signal intensity or the steepness of the inflection point may be influenced by other factors.
The Model
Standard RT-QuIC analysis focuses on a single kinetic metric, the lag time to threshold (i.e. rate of amyloid formation, RAF). However, normalized fluorescence traces frequently exhibit a second kinetic phase — a dampening effect following the initial growth phase — that is poorly captured by single-sigmoidal models. The underlying function is named fit_model() and is described in more detail in the model page.
HAL-QuIC proposes that the full kinetic behavior of an RT-QuIC reaction can be better described by the sum of two logistic functions:
\[ f(t)=\frac{S_1}{1+e^{a_1(b_1-t)}}+\frac{S_2}{1+e^{a_2(b_2-t)}} \]
Each sigmoid has three parameters:
| Parameter | Meaning |
|---|---|
| \(S\) | Asymptote |
| \(a\) | Steepness of the inflection point |
| \(b\) | Time to inflection point |
Together, these six coefficients \((S_1, a_1, b_1, S_2, a_2, b_2)\) provide a compact kinetic fingerprint for any RT-QuIC reaction.