Analysis

  • Q: What do you mean by Target Engagement potency?
    A: The inflection point on the logistic curve obtained in isothermal concentration response series (XC50). It is a measure of the potency of the interaction between the ligand and the molecular protein target in the selected sample matrix (lysate, cells or tissue).
  • Q: What about false negatives?
    A: All proteins melt and can be detected, but they do not always shift. Based on the published literature and our experience at Pelago less than 5% of all proteins do not display a melt curve shift. Most false negatives are either proteins in complex, or have multible membrane spanning domains.
  • Q: What is the false positive rate (FPR) for the CETSA MS technology?
    A: Based on the first Savitski paper, discussions with the academic group and own experience we assume the FPR to be equal to that of CESTA classics: 0%. Of course, in intact cell experiments both CETSA classics and CETSA MS identifies downstream effects – but we do not consider that a false positive.