Mining genome databases via protein mass spectrometry to understand the pregnancy disorder pre-eclampsia Clauser K. R., Foulk R. A., Baker P. R., Fisher S. J. and Burlingame, A. L., Abstract As the post-genomic era arrives, attention is progressing to proteome investigation and elucidation of protein function with correlation to gene expression and regulation. We are studying pre-eclampsia (PE) at the protein level. While normal human pregnancy critically depends on uterine invasion by specialized cells of the placenta (trophoblasts), PE is associated with abnormally shallow trophoblast invasion. As a result the placenta fails to access an adequate supply of maternal blood and becomes hypoxic. Substances released into maternal blood by the hypoxic placenta are thought to cause the maternal signs of PE including dangerously high blood pressure. We modeled this disease by culturing normal chorionic villi (placental tissue containing trophoblasts) in a reduced O environment (2% O2), vs. villi in standard tissue culture conditions (20% O2). 2D PAGE comparison of proteins in conditioned medium from the 2 cultures revealed that the abundances of were regulated by O. Following in-gel tryptic digestion we identified these proteins by searching sequence databases using both peptide-mass fingerprints and fragment-ion tags obtained by MALDI-MS. Fragment-ion tags from MS/MS spectra of individual peptides in sub-picomole quantities of unseparated mixtures yield partial sequence. Recent MS instrumental advances in mass accuracy, sensitivity, and automation, make high-throughput identification of suites of proteins increasingly tractable. Financial support provided by NIH (NCRR BRTP, RR01614, RR08282, HD30367 and HD22210).