Molecular Origin of Blood‐Based Infrared Spectroscopic Fingerprints**

Abstract

Infrared spectroscopy of liquid biopsies is a timeand cost-effective approach that may advance biomedical diagnostics. However, the molecular nature of disease-related changes of infrared molecular fingerprints (IMFs) remains poorly understood, impeding the methods applicability. Here we probe 148 human blood sera and reveal the origin of the variations in their IMFs. To that end, we supplemented infrared spectroscopy with biochemical fractionation and proteomic profiling, providing molecular information about serum composition. Using lung cancer as an example of a medical condition, we demonstrate that the disease-related differences in IMFs are dominated by contributions from twelve highly abundant proteins-that, if used as a pattern, may be instrumental for detecting malignancy. Tying proteomic to spectral information and machine learning advances our understanding of the infrared spectra of liquid biopsies, a framework that could be applied to probing of any disease.

Breast-cancer detection using blood-based infrared molecular fingerprints

“…the person's molecular blood phenotype [22,23]. Even though the IMF of molecularly highly complex blood plasma can only partially be traced back to its molecular origin [24], it may be sensitive and specific to the health state of an individual. In a recent longitudinal study, we have shown that defined workflows to collect, store, process and measure human liquid biopsies lead to reproducible IMFs in healthy, non-symptomatic individuals that are stable over clinically relevant time scales [22,23].…”