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Comparative Mass Spectrometry
The analysis of mass spectra of biological samples (tissue, serum, etc) is a promising avenue towards the discovery of clinically relevant bio-markers. As a starting point, this type of analysis requires a convincing demonstration of the statistical significance of the observed spectral differences between biological samples. Once the significance of observed features is confirmed, the researcher can proceed with further investigation of the molecular nature of the peaks of interest (e.g. aiming at creating the immuno-histochemical assays with satisfactory sensitivity and specificity), or use these features directly for mass-spectrometry based diagnostic tests.
The reliable and reproducible detection of statistically significant differences between mass spectra is a complex problem that involves facing a variety of difficult technical challenges, such as:
  • Dealing with background that can change from spectrum to spectrum, and also within a single spectrum: Any solution requires a reliable background subtraction method.
  • Detecting peaks and other features in the spectra in the presence of noise that can also change substantially, both within a spectrum and from spectrum to spectrum: Any solution requires a method for local estimation of the noise strength.
  • Dealing with spectra misaligned in m/z, due to the (almost always present) slight mis-calibration: Any solution requires a reliable alignment method.
  • Dealing with spectra that do not allow unambiguous classification. Performing classification of the unknown spectrum as belonging to the disease or control group, it is important to be able to quantitatively characterize the confidence of classification, and to recognize and report the spectra that cannot be classified with the required confidence.
  •   Raw mass spectra from the same patient from Colorado University (CU) and Vanderbilt University (VU) before pre-processing.
      Raw mass spectra from the same patient from Colorado University (CU) and Vanderbilt University (VU) after pre-processing.

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    ProTS Marker
    Biodesix Inc has developed ProTS Marker™ - an integrated analysis platform designed specifically for the comparative analysis of mass spectra. ProTS Marker White Paper