Gaedcke, Jochen

[["dc.bibliographiccitation.artnumber","e0197162"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Wolff, Alexander"],["dc.contributor.author","Bayerlová, Michaela"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Beißbarth, Tim"],["dc.date.accessioned","2019-07-09T11:45:42Z"],["dc.date.available","2019-07-09T11:45:42Z"],["dc.date.issued","2018"],["dc.description.abstract","BACKGROUND: Pipeline comparisons for gene expression data are highly valuable for applied real data analyses, as they enable the selection of suitable analysis strategies for the dataset at hand. Such pipelines for RNA-Seq data should include mapping of reads, counting and differential gene expression analysis or preprocessing, normalization and differential gene expression in case of microarray analysis, in order to give a global insight into pipeline performances. METHODS: Four commonly used RNA-Seq pipelines (STAR/HTSeq-Count/edgeR, STAR/RSEM/edgeR, Sailfish/edgeR, TopHat2/Cufflinks/CuffDiff)) were investigated on multiple levels (alignment and counting) and cross-compared with the microarray counterpart on the level of gene expression and gene ontology enrichment. For these comparisons we generated two matched microarray and RNA-Seq datasets: Burkitt Lymphoma cell line data and rectal cancer patient data. RESULTS: The overall mapping rate of STAR was 98.98% for the cell line dataset and 98.49% for the patient dataset. Tophat's overall mapping rate was 97.02% and 96.73%, respectively, while Sailfish had only an overall mapping rate of 84.81% and 54.44%. The correlation of gene expression in microarray and RNA-Seq data was moderately worse for the patient dataset (ρ = 0.67-0.69) than for the cell line dataset (ρ = 0.87-0.88). An exception were the correlation results of Cufflinks, which were substantially lower (ρ = 0.21-0.29 and 0.34-0.53). For both datasets we identified very low numbers of differentially expressed genes using the microarray platform. For RNA-Seq we checked the agreement of differentially expressed genes identified in the different pipelines and of GO-term enrichment results. CONCLUSION: In conclusion the combination of STAR aligner with HTSeq-Count followed by STAR aligner with RSEM and Sailfish generated differentially expressed genes best suited for the dataset at hand and in agreement with most of the other transcriptomics pipelines."],["dc.identifier.doi","10.1371/journal.pone.0197162"],["dc.identifier.pmid","29768462"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15290"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59290"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.haserratum","/handle/2/63504"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.subject.mesh","Burkitt Lymphoma"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Gene Expression Regulation, Neoplastic"],["dc.subject.mesh","High-Throughput Nucleotide Sequencing"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Oligonucleotide Array Sequence Analysis"],["dc.subject.mesh","RNA, Neoplasm"],["dc.subject.mesh","Rectal Neoplasms"],["dc.title","A comparative study of RNA-Seq and microarray data analysis on the two examples of rectal-cancer patients and Burkitt Lymphoma cells."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","394"],["dc.bibliographiccitation.journal","EBioMedicine"],["dc.bibliographiccitation.lastpage","405"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Patzak, Melanie S."],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Patil, Shilpa"],["dc.contributor.author","Hamdan, Feda H."],["dc.contributor.author","Goetze, Robert G."],["dc.contributor.author","Brunner, Marius"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Jodrell, Duncan I."],["dc.contributor.author","Richards, Frances M."],["dc.contributor.author","Pilarsky, Christian"],["dc.contributor.author","Gruetzmann, Robert"],["dc.contributor.author","Rümmele, Petra"],["dc.contributor.author","Knösel, Thomas"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Neesse, Albrecht"],["dc.date.accessioned","2019-07-09T11:50:10Z"],["dc.date.available","2019-07-09T11:50:10Z"],["dc.date.issued","2019"],["dc.description.abstract","BACKGROUND: Cytosolic 5'-nucleotidase 1A (NT5C1A) dephosphorylates non-cyclic nucleoside monophosphates to produce nucleosides and inorganic phosphates. Here, we investigate NT5C1A expression in pancreatic ductal adenocarcinoma (PDAC) and its impact on gemcitabine metabolism and therapeutic efficacy. METHODS: NT5C1A expression was determined by semiquantitative immunohistochemistry using tissue microarrays. Gemcitabine metabolites and response were assessed in several human and murine PDAC cell lines using crystal violet assays, Western blot, viability assays, and liquid chromatography tandem mass-spectrometry (LC-MS/MS). FINDINGS: NT5C1A was strongly expressed in tumor cells of a large subgroup of resected PDAC patients in two independent patient cohorts (44-56% score 2 and 8-26% score 3, n = 414). In contrast, NT5C1A was expressed at very low levels in the tumor stroma, and neither stromal nor tumoral expression was a prognostic marker for postoperative survival. In vitro, NT5C1A overexpression increased gemcitabine resistance by reducing apoptosis levels and significantly decreased intracellular amounts of cytotoxic dFdCTP in +NT5C1A tumor cells. Co-culture experiments with conditioned media from +NT5C1A PSCs improved gemcitabine efficacy in tumor cells. In vivo, therapeutic efficacy of gemcitabine was significantly decreased and serum levels of the inactive gemcitabine metabolite dFdU significantly increased in mice bearing NT5C1A overexpressing tumors. INTERPRETATION: NT5C1A is robustly expressed in tumor cells of resected PDAC patients. Moreover, NT5C1A mediates gemcitabine resistance by decreasing the amount of intracellular dFdCTP, leading to reduced tumor cell apoptosis and larger pancreatic tumors in mice. Further studies should clarify the role of NT5C1A as novel predictor for gemcitabine treatment response in patients with PDAC."],["dc.identifier.doi","10.1016/j.ebiom.2019.01.037"],["dc.identifier.pmid","30709769"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15875"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59716"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2352-3964"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.title","Cytosolic 5'-nucleotidase 1A is overexpressed in pancreatic cancer and mediates gemcitabine resistance by reducing intracellular gemcitabine metabolites."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]