  Previous studies demonstrated that infrared absorption spectra of blood sera
may help disease detection. For clinical translation of this approach, it is
important to determine the molecular origin of disease-related spectral
perturbations. To that end, we supplemented infrared spectroscopy with
biochemical fractionation and proteomic profiling, which provide detailed
information about blood serum composition. We built a model to describe serum
absorption based on the concentrations of the highly-abundant proteins and
applied this framework to lung cancer detection. We find that it is the levels
of acute-phase proteins that change most in the presence of the disease and
generate its infrared signature. These findings inform future clinical trials
and establish a framework that could be applied to probing of any disease.
