Detecting\nHuman Contaminant Genetically Variant Peptides\nin Nonhuman Samples

During proteomics data analysis, experimental spectra\nare searched\nagainst a user-defined protein database consisting of proteins that\nare reasonably expected to be present in the sample. Typically, this\ndatabase contains the proteome of the organism under study concatenated\nwith expected contaminants, such as trypsin and human keratins. However,\nthere are additional contaminants that are not commonly added to the\ndatabase. In this study, we describe a new set of protein contaminants\nand provide evidence that they can be detected in mass spectrometry-based\nproteomics data. Specifically, we provide evidence that human genetically\nvariant peptides (GVPs) can be detected in nonhuman samples. GVPs\nare peptides that contain single amino acid polymorphisms that result\nfrom nonsynonymous single nucleotide polymorphisms in protein-coding\nregions of DNA. We reanalyzed previously collected nonhuman data-dependent\nacquisition (DDA) and data-independent acquisition (DIA) data sets\nand detected between 0 and 135 GVPs per data set. In addition, we\nshow that GVPs are unlikely to originate from nonhuman sources and\nthat a subset of eight GVPs are commonly detected across data sets.