Table III Use of spiked yeast reference to estimate sensitivity and specificity of biomarker candidate discovery

To demonstrate the utility of the reference proteome for benchmarking performance of biomarker discovery strategies, we used the Study 6 spiked yeast reference data to investigate the power of detecting potential biomarkers under typical case-control settings. The data were analyzed using the SASPECT method (25), which uses a probability model to make inferences about protein abundances based on peptide detection. Permutation testing is used to estimate the FDR.

Case sampleNo. identified biomarkersaNo. true positivesbNo. true negativescNo. false positivesdNo. false negativeseSensitivityfSpecificityg
Study 6 SOP (yeast + 0.25 fmol/μl UPS1)002,5220480.001.00
Study 6 SOP (yeast + 0.74 fmol/μl UPS1)442,5220440.081.00
Study 6 SOP (yeast + 2.2 fmol/μl UPS1)25252,5220230.521.00
Study 6 SOP (yeast + 6.7 fmol/μl UPS1)34342,5220140.711.00
Study 6 SOP (yeast + 20 fmol/μl UPS1)49402,513980.83>0.99
  • a Identified biomarkers are proteins with FDR ≤0.01.

  • b True positives (TP) are human proteins identified as “biomarkers” in the SASPECT analysis.

  • c True negatives (TN) are yeast proteins with FDR >0.01.

  • d False positives (FP) are yeast proteins with FDR ≤0.01.

  • e False negatives (FN) are human proteins with FDR >0.01.

  • f Sensitivity is calculated as TP/(TP + FN).

  • g Specificity is calculated as TN/(TN + FP).