The suggested three-step workflow of shotgun proteomics analysis that includes contamination/infection detection.

(1) conventional matching the experimental MS/MS spectra against the protein database of the host organism (human); (2) Unmatched MS/MS spectra and insignificant matches in terms of FDR are matched against viral protein database. (3) The presence of significant hits at the second step points to the potential infection/contamination of the sample. Label-free quantitative analysis of identified proteins (both host and contaminant) provides an estimation of the contamination level and thus severity of the problem.