Systematic comparison of the human saliva and plasma proteomes

Abstract

The proteome of human salivary fluid has the potential to open new doors for disease biomarker discovery. A recent study to comprehensively identify and catalog the human ductal salivary proteome led to the compilation of 1166 proteins. The protein complexity of both saliva and plasma is large, suggesting that a comparison of these two proteomes will provide valuable insight into their physiological significance and an understanding of the unique and overlapping disease diagnostic potential that each fluid provides. To create a more comprehensive catalog of human salivary proteins, we have first compiled an extensive list of proteins from whole saliva (WS) identified through MS experiments. The WS list is thereafter combined with the proteins identified from the ductal parotid, and submandibular and sublingual (parotid/SMSL) salivas. In parallel, a core dataset of the human plasma proteome with 3020 protein identifications was recently released. A total of 1939 nonredundant salivary proteins were compiled from a total of 19 474 unique peptide sequences identified from whole and ductal salivas; 740 out of the total 1939 salivary proteins were identified in both whole and ductal saliva. A total of 597 of the salivary proteins have been observed in plasma. Gene ontology (GO) analysis showed similarities in the distributions of the saliva and plasma proteomes with regard to cellular localization, biological processes, and molecular function, but revealed differences which may be related to the different physiological functions of saliva and plasma. The comprehensive catalog of the salivary proteome and its comparison to the plasma proteome provides insights useful for future study, such as exploration of potential biomarkers for disease diagnostics.

Figure 1

WS protein identifications based on the overlap of the identifications, unique peptide number, and sequence coverage. (A) Venn diagram showing the overlap of the WS proteins between laboratories with total identifications from each group as 1222 CB/UM (CB/UM), 337 RTI (Research Triangle Institute), 447 UCLA, 862 UMN. (B) Number of WS proteins identified as a function of number of unique peptide detected; each bar is demarcated by the number of labs making the identifications. (C) WS protein identifications classified based on protein sequence coverage. The number in parentheses represents the total number of proteins within the sequence coverage range.

Figure 2

Venn diagrams showing the overlapping peptide and protein identifications between WS, parotid/SMSL, and plasma. (A) Peptide identifications; (B) protein identifications.

Figure 3

Comparison of molecular weight and isoelectric point of saliva proteome to plasma proteome and ductal parotid/SMSL saliva proteome to WS proteome.

Figure 4

GO SLIM distributions of saliva proteome, plasma proteome, overlapping proteins of saliva and plasma, and IPI human proteins. (A) Cellular component; (B) biologic process; (C) molecular function.

Figure 5

Venn diagram showing the salivary and plasma overlap in Igs and proteins participating in a KEGG pathway. (A) Igs; (B) carbohydrate metabolism; (C) immune system. (D) cell communication. The number inside the parentheses represents the total number of proteins participating in the pathway from the fluid.

Figure 6

Linear correlation of the unique peptide numbers for the Ig proteins coexisting in WS, parotid, SMSL, and plasma. Each point represents an overlapping Ig protein. (A) Correlation of Ig proteins in WS and plasma; (B) correlation of Ig proteins in parotid and plasma; (C) correlation of Ig proteins in SMSL and plasma. The straight line shows that the number of unique peptides used for the Ig identifications in WS, parotide, or SMSL has a linear correlation with the number of the peptides used for the plasma Ig identifications.