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Among the different biomolecules found in human saliva, proteins are among the most prominent. Proteins carry out many vital roles in saliva, from enzymatic catalysis to structure. Proteins also have great potential as diagnostic biomarkers, which can be easily collected using non-invasive methods. In order to catalog salivary proteins, and determine those with diagnostic potential for human disease and other health conditions, mass spectrometry-based proteomic technologies have been used over the last decade or more. Using these conventional technologies, several thousand proteins have been identified in whole saliva, with numerous studies identifying proteins with diagnostic promise for a variety of health conditions. In addition, these technologies have been used to identify proteins expressed by microbial communities in human saliva. In recent years, new mass spectrometry-based proteomics technologies have emerged that are giving researchers new tools for characterizing the proteome of whole saliva, as well as other biological sample types. Two of the most promising of these new technologies include methods for “data-independent acquisition”, which allows for large-scale hypothesis-driven proteomic discovery studies, and proteogenomics, a bioinformatics-driven approach which integrates genomic and proteomic data to characterize novel gene products missed by conventional methods. This paper will summarize the efforts of cataloging the saliva proteome to-date, including highlights of studies identifying salivary protein biomarkers of disease. In addition, the emerging technologies of data-independent acquisition and proteogenomics will be described, along with their potential in characterizing the saliva proteome for diagnostic applications.
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