MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/x01/MSV000080263/primaryOK2000000ProteomicsDr Eleftherios P. DiamandisQ ExactiveHomo Sapiens (ncbitaxon:9606)https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=90f46bded144485c8f83b33387cff812MassIVE75MOD:00397 - "A protein modification that is produced by reaction with iodoacetamide, usually replacement of a reactive hydrogen with a methylcarboxamido group."MOD:00425 - "A protein modification that effectively replaces one hydrogen atom with a hydroxyl group."MOD:00394 - "A protein modification that effectively replaces a hydrogen atom with an acetyl group."<h4>Background</h4>Urine represents an ideal source of clinically relevant biomarkers as it contains a large number of proteins and low molecular weight peptides. The comprehensive characterization of the normal urinary proteome and peptidome can serve as a reference for future biomarker discovery. Proteomic and peptidomic analysis of urine can also provide insight into normal physiology and disease pathology, especially for urogenital diseases.<h4>Methods</h4>We developed an integrated proteomic and peptidomic analytical protocol in normal urine. We employed ultrafiltration to separate protein and peptide fractions, which were analyzed separately using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) on the Q-Exactive mass spectrometer.<h4>Results</h4>By analyzing six urines from healthy individuals with advanced age, we identified 1754 proteins by proteomic analysis and 4543 endogenous peptides, arising from 566 proteins by peptidomic analysis. Overall, we identified 2091 non-redundant proteins by this integrated approach. In silico protease activity analysis indicated that metalloproteases are predominantly involved in the generation of the endogenous peptide signature. In addition, a number of proteins that were detected in normal urine have previously been implicated in various urological malignancies, including bladder cancer and renal cell carcinoma (RCC).<h4>Conclusions</h4>We utilized a highly sensitive proteomics approach that enabled us to identify one of the largest sets of protein identifications documented in normal human urine. The raw proteomics and peptidomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD003595.Eight pulmonary valve replacements (PVR) have been performed from January 1992 to October 1994. Three patients (mean age 7.7 years, range two to 16 years) had absent pulmonary valve with tetralogy of Fallot and underwent primary PVR at the time of surgical correction. Five other patients, who had correction of tetralogy of Fallot (four cases) and of double outlet right ventricle with ventricular septal defect and pulmonary stenosis (one case), were reoperated for pulmonary regurgitation with progressive right ventricular dysfunction. Mean age at the time of reoperation was 18 years (range seven to 34 years). There was no early death. Early postoperative recovery was satisfactory in all of them. The follow up ranges from six to 35 months (mean 19 months). Seven patients were in functional class I and one in functional class II when they were last evaluated in the out-patient department and five of them were off diuretics and vasodilator. In the presence of right ventricular dysfunction pulmonary regurgitation is poorly tolerated. A competent and non-obstructive pulmonary valve is often life saving in these critically ill patients.An integrated proteomic and peptidomic assessment of the normal human urinome.Orthotopic pulmonary valve replacement with a homograft.Di Meo Ashley A, Batruch Ihor I, Yousef Arsani G AG, Pasic Maria D MD, Diamandis Eleftherios P EP, Yousef George M GMSaha K K, Iyer K S KS, Sharma R R, Bhan A A, Airan B B, Venugopal P Pliquid chromatography tandem mass spectroscopy, Biological Markers, Viral Marker, Surrogate Endpoints, Bladder Tumor, clear cell renal cell adenocarcinoma, Collecting Duct, Molecular Weights, determination, Tandem, Laboratory, cancer of the urinary bladder, Biochemical, Mbp1, Endpoint, adenocarcinoma of kidney, bladder cancer, protein, Serum, Tumor, Mass Spectrometry Mass Spectrometry, Papillary Renal Cell Carcinoma, CCRCC, peptide, Polypeptides, Laboratory Markers, Donor Artificial Insemination, protein polypeptide chains, Adenocarcinoma Of Kidneys, peptido, diseases, Renal Cell Adenocarcinomas, Urinary Bladder Cancer, Biological, CDA2, diseases and disorders, RCC, cytopathology, protein aggregate, myd, acting on D-amino acid peptides, Donor Artificial, Bladder Neoplasm, average, me75, human disease, LCMSMS, Hypernephromas, peptides, Molecular, Metallopeptidases, Cancer of the Bladder, Mbp-1, Weights, proteins, Mass Spectrometry, D17Mit170, T1, peptide hydrolase activity, clear cell renal cell carcinoma, Immune, Markers, urinary aspects, malignant neoplasm, Viral Markers, Pathologies, Homo sapiens disease, Renal Collecting Duct Carcinoma, Malignancies, Tumors, LC-MS2, Cancer of Bladder, Carcinoma, Adenocarcinoma Of, Viral, Bladder Cancers, Surrogate Endpoint, gyltl1b-b, Liquid Chromatography, LC-MS/MS, Urinary Bladder Neoplasm, Bladder Tumors, Biochemical Markers, Renal Cell Adenocarcinoma, Adenocarcinoma Of Kidney, Tl3, Biologic Marker, Tl2, Renal Cell Carcinoma, Adenocarcinomas, tumor of the bladder, Collecting Duct Carcinoma of the Kidney, Clear Cell Renal Cell Carcinoma, Benign, peptidase activity, Marker, MDDGA6, mKIAA0609, Weight, Diseases, Heterologous Insemination, Metallopeptidase, KIAA0609, Hypernephroma, cancer of bladder, Carcinomas, fg, kidney adenocarcinoma, gyltl1b, histopathology, End Points, MS/MS, Kidney, Malignant Tumor of Urinary Bladder, mdc1d, expanded, Benign Neoplasms, Immunologic, Laboratory Marker, Nephroid, study protocol, Renal Cell Cancer, Malignant Neoplasms, Papillary, MDC1D, disease, Artificial Insemination, enr, enlarged, Biochemical Marker, liquid chromatography-tandem mass spectroscopy, Collecting Duct Carcinoma (Kidney), renal cell carcinoma, Polypeptide, Nephroid Carcinoma, Proteomes, Urinary Bladder, urinary bladder cancer, Clear Cell Renal Carcinoma, Adenocarcinoma, big, other disease, Clinical Markers, Clinical Marker, Neoplasms, number, Renal Cell Cancers, Benign Neoplasm, Gene, Renal Adenocarcinomas, protein-containing complex, Malignant, AID, Aid, froggy, Gyltl1a, LC-MS-MS, Surrogate End Points, Surrogate Markers, large, method, Hypernephroid, Metalloprotease, polypeptide chain, method used in an experiment, Sarcomatoid Renal Cell Carcinoma, LC-MSMS, Gene Products, disease or disorder, Hypernephroid Carcinomas, Low, Renal Carcinomas, Hypernephroid Carcinoma, BLC, hypernephroma, Grawitz Tumor, aid, Insemination, Biomarker, study, urinary levels, Clinical, Malignancy, MDDGB6, MS2, Biological Marker, Collecting Duct Carcinoma, Renal, LARGE, Metalloproteinase, non-neoplastic, Neoplasias, BPFD#36, Immunologic Markers, acting on L-amino acid peptides, HEL-S-284, great, disorder, peptidos, HIGM2, biological marker, acting on peptide bonds, hydrolase, Collecting Duct Carcinomas (Kidney), Immunologic Marker, Biologic, Heterologous, Cancer, Grawitz, protease activity, cou, cancer of the bladder, Malignant Neoplasm, Immune Markers., protein complex, Chromophil Renal Cell Carcinoma, Collecting Duct Carcinomas, Serum Markers, Proteins, disorders, End Point, total expressed protein, Renal Cell Carcinomas, medical condition, function, Renal Adenocarcinoma, Peptide, Immune Marker, Human Donor, polypeptide, Chromophobe Renal Cell Carcinoma, LC/MS/MS, renal cell adenocarcinoma, Lr, MT, native protein, natural protein, Surrogate End Point, Protein, chemical analysis, proteomic analysis, Neoplasm, condition, Donor, Nephroid Carcinomas, Bladder Neoplasms, tandem MS, Biologic Markers, Artificial, Serum Marker, primary cancer, Bladder, Surrogate, Arp2, Metalloproteinases, ARP2, Renal Cell, Renal Carcinoma, Endpoints, Mass Spectrometry-Mass Spectrometry, Cancers, malignant tumor, Surrogate Marker, Protein Gene Products, plan specification, Gene Proteins, proteinase activity, Bladder Cancer, Collecting Duct (Kidney), cardinality, Bra, liquid chromatography tandem mass spectrometry, Peptid, assay, biopsy, cancer of urinary bladder, Neoplasia, Immune Markersliquid chromatography tandem mass spectroscopy, Bru, Biological Markers, Viral Marker, Urogenital Disease, Surrogate Endpoints, Bladder Tumor, clear cell renal cell adenocarcinoma, Collecting Duct, Molecular Weights, Raw, determination, Tandem, Laboratory, cancer of the urinary bladder, Biochemical, Mbp1, Endpoint, adenocarcinoma of kidney, bladder cancer, protein, Serum, Tumor, Mass Spectrometry Mass Spectrometry, Papillary Renal Cell Carcinoma, CCRCC, peptide, Polypeptides, Laboratory Markers, Techniques, protein polypeptide chains, Adenocarcinoma Of Kidneys, peptido, diseases, Renal Cell Adenocarcinomas, Urinary Bladder Cancer, Biological, Method, diseases and disorders, RCC, cytopathology, protein aggregate, myd, acting on D-amino acid peptides, Bladder Neoplasm, average, Svc, me75, human disease, LCMSMS, Hypernephromas, Man (Taxonomy), peptides, Molecular, Metallopeptidases, Cancer of the Bladder, Mbp-1, Weights, Futurology, proteins, Mass Spectrometry, procedures, D17Mit170, T1, peptide hydrolase activity, allergic reaction, clear cell renal cell carcinoma, Immune, Markers, Methodological Studies, urinary aspects, Viral Markers, Pathologies, Homo sapiens disease, Malignancies, Renal Collecting Duct Carcinoma, Predictions and Projections, Tumors, LC-MS2, Data Set., Cancer of Bladder, Carcinoma, Adenocarcinoma Of, Viral, Bladder Cancers, Surrogate Endpoint, gyltl1b-b, Modern, Liquid Chromatography, LC-MS/MS, Urinary Bladder Neoplasm, Bladder Tumors, Biochemical Markers, Renal Cell Adenocarcinoma, Adenocarcinoma Of Kidney, Procedure, Tl3, Biologic Marker, Tl2, Renal Cell Carcinoma, Adenocarcinomas, Genitourinary Diseases, tumor of the bladder, Collecting Duct Carcinoma of the Kidney, Clear Cell Renal Cell Carcinoma, Benign, peptidase activity, Marker, MDDGA6, mKIAA0609, RENBP, Weight, Diseases, Metallopeptidase, KIAA0609, Hypernephroma, cancer of bladder, Carcinomas, fg, kidney adenocarcinoma, gyltl1b, histopathology, End Points, MS/MS, Kidney, Malignant Tumor of Urinary Bladder, mdc1d, expanded, Benign Neoplasms, Immunologic, Methodological, Laboratory Marker, Nephroid, study protocol, Methodological Study, human, Renal Cell Cancer, AGE, Malignant Neoplasms, Papillary, MDC1D, disease, enr, enlarged, Biochemical Marker, liquid chromatography-tandem mass spectroscopy, Collecting Duct Carcinoma (Kidney), Urogenital, renal cell carcinoma, Polypeptide, Nephroid Carcinoma, Proteomes, Urinary Bladder, humans, urinary bladder cancer, Clear Cell Renal Carcinoma, Adenocarcinoma, big, other disease, human being, Procedures, Clinical Markers, Peptidomics, Clinical Marker, Neoplasms, Benign Neoplasm, Renal Cell Cancers, Gene, Renal Adenocarcinomas, protein-containing complex, Malignant, froggy, Gyltl1a, LC-MS-MS, Surrogate End Points, Human, Surrogate Markers, large, method, Hypernephroid, Metalloprotease, polypeptide chain, Homo sapiens, sensitive, method used in an experiment, Sarcomatoid Renal Cell Carcinoma, LC-MSMS, Gene Products, Studies, disease or disorder, Projections and Predictions, Hypernephroid Carcinomas, Low, Del(8)44H, Renal Carcinomas, Hypernephroid Carcinoma, BLC, Technique, hypernephroma, sensitivity, Man, Grawitz Tumor, Biomarker, urinary levels, Clinical, Malignancy, MDDGB6, MS2, Biological Marker, Collecting Duct Carcinoma, Renal, LARGE, Metalloproteinase, non-neoplastic, Study, Neoplasias, BPFD#36, Immunologic Markers, acting on L-amino acid peptides, great, disorder, peptidos, biological marker, acting on peptide bonds, hydrolase, Collecting Duct Carcinomas (Kidney), Immunologic Marker, Biologic, Cancer, Grawitz, Genitourinary, protease activity, Disease, cou, Malignant Neoplasm, cancer of the bladder, protein complex, RnBP, Chromophil Renal Cell Carcinoma, Collecting Duct Carcinomas, Serum Markers, Proteins, disorders, End Point, total expressed protein, GlcNAc 2-epimerase, Renal Cell Carcinomas, function, medical condition, Renal Adenocarcinoma, Peptide, Immune Marker, polypeptide, Chromophobe Renal Cell Carcinoma, LC/MS/MS, N-acetyl-D-glucosamine 2-epimerase, renal cell adenocarcinoma, Lr, native protein, natural protein, Surrogate End Point, Protein, chemical analysis, proteomic analysis, Neoplasm, condition, Nephroid Carcinomas, techniques, Genitourinary Disease, Bladder Neoplasms, tandem MS, Biologic Markers, Serum Marker, Col4a-1, Bladder, Surrogate, Metalloproteinases, Renal Cell, Renal Carcinoma, Endpoints, Mass Spectrometry-Mass Spectrometry, Cancers, Surrogate Marker, Protein Gene Products, plan specification, Gene Proteins, proteinase activity, Bladder Cancer, Collecting Duct (Kidney), Modern Man, Bra, renin-binding protein, liquid chromatography tandem mass spectrometry, Peptid, assay, biopsy, cancer of urinary bladder, Future, Neoplasia, methodology, Immune MarkersHuman, average, humans., human being, Man (Taxonomy), Homo sapiens, Man, human, Modern Man, ModernHuman, total expressed protein, human being, Man (Taxonomy), Homo sapiens, Man, human, Modern Man, humans, Proteomes., Modern0PXD003595trueCharacterization of the human urinary proteome and peptidomeUrine represents an ideal source of clinically relevant biomarkers since it contains a large number of proteins and low molecular weight peptides. Characterization of the normal urinary proteome and peptidome can serve as a reference for disease and can aid in biomarker discovery. Proteomic and peptidomic analysis of urine can also provide insight into normal physiology and disease pathology, especially for urogenital diseases. We developed an integrated proteomic and peptidomic analytical protocol for normal urine. We employed ultrafiltration to separate protein and peptide fractions, which were analyzed separately using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) on the Q-Exactive mass spectrometer. By analyzing six urines from healthy individuals, we identified 1754 proteins by proteomic analysis and 4543 endogenous peptides, arising from 566 proteins by peptidomic analysis. Overall, we identified 2091 non-redundant proteins by this integrated approach. In silico protease activity analysis indicated that metalloproteases are predominantly involved in the generation of the endogenous peptide signature. In addition, a number of proteins that were detected in normal urine have previously been implicated in various urological malignancies, including bladder cancer and renal cell carcinoma. Thus, this study can provide a reference for assessing alterations in cancer-specific biomarkers.Fri Oct 21 13:20:00 BST 2016MSV00008026327394047