P ro t eo m ics pro j ec t s
First draft of the human ductal salivary proteome
were identified from 23 subjects. The researchers detected 914 proteins in parotid secretions and 917 in submanAlthough proteomics groups that study dibular and sublingual (SM/SL) fluid. blood often refer to collection of this Although many proteins were common sample as a “noninvasive” procedure, to parotid and SM/SL fluids, some many patients on the other end of the unique constituents were observed. needle would beg to differ. Thus, more Most of the abundant proteins in the researchers are turning to alternative salivary proteome were detected by bodily fluids, such as urine and saliva. all three groups, but less abundant Unlike blood draws, whole-saliva colproteins often were identified by a lection does not require trained personsingle group. As expected, the proteome nel. The subject just spits. Also, spitting was enriched for extracellular into a tube does not bring up the proteins. The group found that same privacy issues that urine several proteins in saliva are collection does. “The compli(a) present in tears; both of these ance is high,” says David Wong of fluids are produced by serous the University of California Los glands, so the similarity of the Angeles (UCLA). “I have yet to protein components was not come across either a 4-year-old or surprising. a 96-year-old who says, ‘David, I Although the consortium ofwon’t give you a sample.’” ficially ended earlier this year, Aside from the patient perthe researchers plan to continspective, scientific reasons also ue their saliva research. Wong’s factor into the decision to study group is developing biosensors saliva. Many plasma proteins to measure proteome changes are present in saliva. In addition, (b) in small samples. To further the dynamic range of proteins in explore the similarities and saliva is not as large as in plasma, differences between saliva and and this is sometimes an advanplasma, his lab also is working tage, explains Joe Loo of UCLA. with Gil Omenn who is at the Although interest in studyUniversity of Michigan and is ing saliva is growing, little is involved with HUPO’s Plasma known about the components Proteome Project. Wong, Loo, of pure salivary secretions. To Paul Denny at USC, and colremedy this, the National Instileagues in the UCLA/USC tute of Dental and Craniofacial group are analyzing salivary Research (NIDCR) at the U.S. proteins from subjects with varNational Institutes of Health Collecting ductal saliva. To collect parotid fluid, (a) two Lashious diseases. The UCSF group, funded three major research colley cups are placed in a subject’s mouth against the left and led by Fisher, plans to analyze laborations under a cooperative right sides of the cheek. SM/SL fluids are collected with (b) a saliva from additional subjects agreement to form a consortium Block and Brotman collector placed under a subject’s tongue. to study variations between that would characterize the individuals and posttranslanormal ductal salivary proteome. tional modifications. To figure out what that the consortium probed deeper The three groups—from UCLA; the the proteins of the salivary proteome into the proteome than previous efforts University of Southern California (USC), are doing, John Yates’s team at TSRI is have, and the researchers took the extra the University of California San Franconducting functional studies in colstep of validating some of the identicisco (UCSF), and the Scripps Research laboration with Hagen’s group. Hagen fied proteins. A unique aspect of the Institute (TSRI); and the University of also is involved in a biosensor project study was the wide range of methods Rochester (U of R)—applied separately with Frank Oppenheim and Fred Little applied to the proteome. With this for the NIDCR funding. Although each of Boston University, David Walt of Tufts multipronged approach, “not only do of the three groups collected and anaUniversity, John McDevitt of the Univeryou validate each other’s identificalyzed its own samples on a daily basis, sity of Texas Austin, and Mark Sullivan, tions by overlap, but you cover more of the teams gathered a few times a year to also of U of R. This group, led by Sullia proteome,” notes Fred Hagen of U of make sure they were meeting NIDCR’s van, is developing diagnostic antibodies R. Fisher explains, “If you use different goals. Ultimately, all of the data were against the saliva proteome. approaches and different instrumentapooled and analyzed as one large data All of the data generated by the saliva tion, you’ll get different results. We set. The 4-year project resulted in the consortium are publicly available at wanted to . . . cast our net as widely as publication of a catalog and a prelimiwww.hspp.ucla.edu. possible.” nary analysis of ductal salivary proteins —Katie Cottingham A total of 1166 nonredundant proteins (J. Proteome Res. 2008, 7, 1994–2006). MARKUS HARDT, UCSF
Several factors set this consortium and its work apart from previous saliva proteomics efforts. One of the biggest differences is that most published papers report proteins of whole saliva (spit). However, “This project focused on pure, pristine ductal fluids before they come out into the oral cavity and mingle with bugs and other things that could complicate the picture,” explains Wong. Other important differences, as Susan Fisher of UCSF points out, are
2592 Journal of Proteome Research • Vol. 7, No. 7, 2008
