{"database":"PAXDB","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["http://pax-db.org/downloads/latest/datasets/bioprojects-abundance-files-v4.0.zip"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":0,"searchCount":0},"additional":{"omics_type":["Proteomics"],"submitter":["Christian von Mering"],"species":["9606"],"full_dataset_link":["https://pax-db.org/dataset/9606/4148541313"],"submitter_email":["mering@imls.uzh.ch"],"submitter_affiliation":["University of Zurich"],"sample_protocol":[""],"repository":["PAXDB"],"data_protocol":["For the rescaling, the\ndatasets are first parsed or processed such that the data reflect\nproportional abundances of whole protein molecules\n(i.e. proportionality to counts of complete, individual protein\nmolecules, not to molecular weights, protein volumes, or digested\npeptides). In the case of spectral counting data protein. The proportional abundances are rescaled linearly to add up\nto one million; this means the abundance of each protein of\ninterest is finally expressed in (parts per million,) relative to\nall other proteins in a sample. \nFor a given protein abundance dataset, we then compute\nthe absolute log abundance ratios of all pairs of proteins\nannotated to be functionally linked. The median of these absolute\nlog abundance ratios represents an indirect quality\nmetric: the closer it is to zero, the better (i.e. the more there\nis consistency between abundance values and functional annotations\nsuch as protein complexes or pathways). We then\ncompute a background expectation for this metric, by permuting\nthe abundance values in a given dataset randomly,\nand recomputing the median log abundance ratios. The permutation\nis repeated several times, yielding a distribution of\nmedians. The actually observed median is then expressed as a\nZ-score distance to the random distribution ofmedians—this\ndistance is termed the interaction consistency score."],"pubmed_abstract":["Many patients with pancreatic cancer have metastases to distant organs at the time of initial presentation. Recent studies examining the evolution of pancreatic cancer at the genetic level have shown that clonal complexity of metastatic pancreatic cancer is already initiated within primary tumors, and organ-specific metastases are derived from different subclones. However, we do not yet understand to what extent the evolution of pancreatic cancer contributes to proteomic and signaling alterations. We hypothesized that genetic heterogeneity of metastatic pancreatic cancer results in heterogeneity at the proteome level. To address this, we employed a model system in which cells isolated from three sites of metastasis (liver, lung, and peritoneum) from a single patient were compared. We used a SILAC-based accurate quantitative proteomic strategy combined with high-resolution mass spectrometry to analyze the total proteome and tyrosine phosphoproteome of each of the distal metastases. Our data revealed distinct patterns of both overall proteome expression and tyrosine kinase activities across the three different metastatic lesions. This heterogeneity was significant because it led to differential sensitivity of the neoplastic cells to small molecule inhibitors targeting various kinases and other pathways. For example, R428, a tyrosine kinase inhibitor that targets Axl receptor tyrosine kinase, was able to inhibit cells derived from lung and liver metastases much more effectively than cells from the peritoneal metastasis. Finally, we confirmed that administration of R428 in mice bearing xenografts of cells derived from the three different metastatic sites significantly diminished tumors formed from liver- and lung-metastasis-derived cell lines as compared with tumors derived from the peritoneal metastasis cell line. Overall, our data provide proof-of-principle support that personalized therapy of multiple organ metastases in a single patient should involve the administration of a combination of agents, with each agent targeted to the features of different subclones."],"pubmed_title":["Heterogeneity of pancreatic cancer metastases in a single patient revealed by quantitative proteomics."],"pubmed_authors":["Kim Min-Sik MS, Zhong Yi Y, Yachida Shinichi S, Rajeshkumar N V NV, Abel Melissa L ML, Marimuthu Arivusudar A, Mudgal Keshav K, Hruban Ralph H RH, Poling Justin S JS, Tyner Jeffrey W JW, Maitra Anirban A, Iacobuzio-Donahue Christine A CA, Pandey Akhilesh A"],"data_synonyms":["Add, DmelCG43443, ADD, ADD-87, Hts-RC, data, AU023367, Data Set, protein complex, supply, Proteins, Ovhts, Gene, HtsRC, CG9325, protein, neutral molecular compounds, protein-containing complex, Dmel_CG9325, Xt, Peptide, 1B1, add, Polypeptides, anon-EST:Posey9, protein polypeptide chains, native protein, peptido, htsRC, GLI3-190, natural protein, polypeptide chain, Add-hts, Protein, CG43443, Gene Products, l(2)k14523, Dmel_CG34197, l(2)00634, median, Ovhts-RC, background, supply and distribution, protein aggregate, all_pairs, molecule, Bph, molecula, Random selection by shearing, oligonucleotide random primer, proportion, HTS-R1, HTS, Hts, molecules, peptides, l(2)k06121, adducin, GLI3FL, distribution, AI854843, proportionality, add-like, HTS-RC, rate, proteins, Molekuel, Pdn, sample population, introduction, Protein Gene Products, Gene Proteins, Adducin, RANDOM, 10^[-6], ppm, sample, supply., quotient, Peptid, peptidos, Polypeptide, Attention Deficit Hyperactivity Disorder, l(2)01103, EST D, CG34197, HtsF, ratio"],"description_synonyms":["metastatic."],"pubmed_title_synonyms":["Pancreatic Carcinomas, Carcinomas, Peptidomics., malignant neoplasm of tail of pancreas, Carcinoma, pancreatic tumor, Cancer of Pancreas, Pancreatic Carcinoma, malignant neoplasm of head of pancreas, Neoplasms, Acinar Carcinoma, malignant neoplasm of body of pancreas, pancreatic neoplasm, familial, number, Pancreas Cancer, pancreas, patient, Cancers, Pancreatic Cancers, Pancreas, Pancreas Cancers, Client, presence, Pancreas Neoplasm, Pancreatic Neoplasm, Pancreatic Acinar Carcinoma, count in organism, Ca tail of pancreas, Ca head of pancreas, Ca body of pancreas, Patient, Pancreatic Cancer, Clients, heterogeneity, Neoplasm, Pancreatic Acinar, pancreatic carcinoma, Pancreatic, Cancer of the Pancreas, PNCA, Pancreas Neoplasms, Pancreatic Acinar Carcinomas, Acinar Carcinomas, pancreatic tumour, pancreas neoplasm, Cancer"],"name_synonyms":["l(3)Ca, mCRY, titin, Cell Lines, 26S protease, l(3)62Ca, d-titin, 0020/01, threonine endopeptidase activity, Mbh1, SLS, Sls, Cell, ingensin, kettin, large multicatalytic protease, CFU-MC, HEL-S-66, Line, DmelCG1915, Titin, prosome, Crry, multicatalytic endopeptidase complex, anon-CREST, Ket, CFU-Mast, tricorn proteinase, D-titin, l(3)j1D7, Lines, AFCP, colony forming unit mast cell, D-Titin, CG18857, MIC10, ket, sam, sal, TLX, l(3)dre8, lens neutral proteinase, metastatic, CG1915, CT41299, multicatalytic proteinase (complex), proteasome endopeptidase complex., KZ, polyhedral organelle, l(3)S002001, l(3)rL182, CG18242, tricorn protease, AHUS2, TRA2.10, Mcp, MCP, alkaline protease, multicatalytic proteinase, CG18245"],"pubmed_abstract_synonyms":["extent, para Tyrosine, Parametriums, Metastasis, Laboratory, Heterograft, Mus domesticus, Addresses, Neoplasm Metastases, CASP-14, neoplasm metastasis, TRANSPL HETEROL, House Mouse, Pancreatic Neoplasm, Long Term, element, cancer metastasis, dmTAF[[II]]230, Ca tail of pancreas, Ca head of pancreas, Kinase Inhibitors, parenchyma of lung, Tyrosine Kinase Inhibitor, Line, Inhibitors, Kinase, Analysis, Effect, organ, Mass Spectrum Analysis, treatment, TFIID TAF250, Analyses, cel, 2-amino-3-(4-hydroxyphenyl)propanoic acid, 3-(p-Hydroxyphenyl)alanine, tyrosine kinase inhibitors, iecur, Swiss Mice, Pancreatic Cancers, Y, genetic, allergic reaction, Xenotransplantations, signaling process, Tyr, disease management, Therapies, Parietal Peritoneum, ATP Phosphotransferases, tyrphostin, Pancreatic Acinar Carcinomas, Long-Term Effects, ATP, pancreatic tumour, pancreas neoplasm, single organism signaling, Tyrosine Protein Kinase Inhibitors, Therapy, Carcinoma, dTAF[[II]]230, pulmo, completeness, malignant neoplasm of body of pancreas, familial, 2-Amino-3-(p-hydroxyphenyl)propionic acid, mouse, Longterm Effect, lung parenchyma, TAF200, para-Tyrosine, TAFII-250, TAF250/230, Spectrum Analysis, results, TKI Tyrosine Kinase Inhibitors, Feature., Tyrosine, Spectroscopy, TAFII250, Mini-ICE, tyrphostins, pancreatic carcinoma, Pancreatic, Cancer of the Pancreas, Heterologous Transplantations, neoplasms, Lines, Carcinomas, Mus musculus, Xenograft, Transphosphorylases, Xenotransplantation, Cancer of Pancreas, Caspase-14 subunit p10, Transplantation, malignant neoplasm of head of pancreas, mice, Heterogeneity, L-isomer, Swiss Mouse, Spectrometry, Caspase-14 subunit p19, Xenografts, MICE, CG17603, Features, TAF[[II]], Pancreas, Treatments, Tyrosine Kinase, Pancreatic Acinar Carcinoma, L isomer, domesticus, organ system, metastatic, Patient, Ca body of pancreas, pulmonary, Specificity and Sensitivity, antagonists and inhibitors, Taf250, SR3-5, inherited genetic, L-Tyrosine, Mouse, PNCA, Proteomes, Acinar Carcinomas, TAF230, 3.4.22.-, biological signaling, d230, Effects, Neoplasms, TKI inhibitor, number, Pancreas Cancer, mini-ICE, dTAFII250, pancreas, Spectrum Analyses, Transplantations, EfW1, Pancreas Cancers, body system, presence, heterologous transplantation, jecur, House, dmTAF1, Pancreatic Cancer, sensitive, Taf230, Genetic heterogeneity, lung, Mass, Mus musculus domesticus, Pancreatic Acinar, system, Parietal, neoplasm, Mice, sensitivity, Phosphotransferase, Mass Spectroscopy, TAF250, Pancreatic Carcinomas, tumor cell migration, Taf200, anatomical systems, TKI inhibitors, dTAF[[II]]250, Genetic, Genetic Heterogeneities, Longterm, Swiss, cell, Pancreatic Carcinoma, Acinar Carcinoma, inhibiteur, Heterografts, metastasis, Taf1p, Long-Term, Transphosphorylase, peritoneum, dTAF250, inhibidor, L Tyrosine, protein tyrosine kinase inhibitors, anatomical unit, Clients, body organ, heterogeneity, Visceral Peritoneum, Sensitivity, Long-Term Effect, Characteristics, Tyrosin, TAF, constitutitional genetic, tumor metastasis, Heterologous, Cancer, Peritoneum, inhibitors, data, TAF[[II]]250, Visceral, Metastases, pancreatic neoplasm, Cell Lines, total expressed protein, inhibitor, l(3)84Ab, BG:DS00004.13, Client, Pancreas Neoplasm, Cell, Phosphotransferases, dTAF230, Metastase, count in organism, MS, XENOTRANSPL, Characteristic, tirosina, Mus, p230, Long Term Effects, Neoplasm, protein tyrosine kinase inhibitor, TAF[[II]]250/230, TFIID, connected anatomical system, Mass Spectrum Analyses, antagonists, Taf[[II]]250, malignant neoplasm of tail of pancreas, Mass Spectrum, pancreatic tumor, TAF[[II]]230, distinct, Kinases, Specificity, Heterogeneities, House Mice, HETEROL TRANSPL, patient, TAF[II]250, Cancers, Longterm Effects, signalling, Laboratory Mice, Livers, Parametrium, DmelCG17603, signalling process, Therapeutic, Treatment, Lungs, peritonaeum, Pancreas Neoplasms, hereditary, Laboratory Mouse, TAF1"],"citation_count":["0"],"additional_accession":[]},"is_claimable":false,"name":"H.sapiens - Cell line, Pancreatic metastatic, SC (Kim,mcp,2014)","description":"abundance based on Spectral counting, Pancreatic_metastatic, Interaction consistency score: 21.5, Coverage: 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