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  • PATHWAY  (6)
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  • 1
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    Genome Biology 7 (7), Art.Nr.R66- 
    Keywords: Germany ; PATHWAY ; PATHWAYS ; screening ; GENOME ; RNA ; COMPONENTS ; IDENTIFICATION ; MICROARRAY DATA ; CAENORHABDITIS-ELEGANS ; STATISTICAL-ANALYSIS ; PHENOTYPE ; DOUBLE-STRANDED-RNA ; INTEGRATION ; RE ; INTERFERENCE ; RNA INTERFERENCE ; STANDARDS ; GENETIC INTERFERENCE ; FUNCTIONAL-CHARACTERIZATION ; TECHNOLOGY ; technique ; BIOCONDUCTOR
    Abstract: RNA interference (RNAi) screening is a powerful technology for functional characterization of biological pathways. Interpretation of RNAi screens requires computational and statistical analysis techniques. We describe a method that integrates all steps to generate a scored phenotype list from raw data. It is implemented in an open-source Bioconductor/R package, cellHTS (http://www.dkfz.de/signaling/cellHTS). The method is useful for the analysis and documentation of individual RNAi screens. Moreover, it is a prerequisite for the integration of multiple experiments
    Type of Publication: Journal article published
    PubMed ID: 16869968
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  • 2
    Keywords: CELLS ; EXPRESSION ; SURVIVAL ; Germany ; IN-VIVO ; PATHWAY ; VIVO ; GENE ; GENE-EXPRESSION ; PROTEIN ; RNA ; transcription ; NF-KAPPA-B ; ACTIVATION ; INFECTION ; TRANSCRIPTION FACTOR ; IMMUNE-RESPONSES ; TARGET ; Drosophila ; MELANOGASTER ; REQUIRES ; HOMOLOG ; IMMUNE-RESPONSE ; FUNCTIONAL GENOMICS ; HOST-DEFENSE ; INTERFERENCE ; RNA INTERFERENCE ; innate immune responses ; IMMUNE ; TOLL ; FUNGAL-INFECTIONS ; Toll signalling
    Abstract: Innate immune signalling pathways are evolutionarily conserved between invertebrates and vertebrates. The analysis of NF-kappa B signalling in Drosophila has contributed important insights into how organisms respond to infection. Nevertheless, significant gaps remain in our understanding of how the activation of intracellular signalling elicits specific transcriptional programs. Here we report a genome-wide RNA interference survey for transcription factors that are required for Toll-dependent immune responses. In addition to the NF-kappa B homologs Dif, Dorsal and factors of the general transcription machinery, we identified Deformed Epidermal Autoregulatory Factor 1 (Deaf1) to be required for the expression of the Toll target gene Drosomycin in cultured cells and in Drosophila in vivo. We show that Deaf1 is required for the survival of flies after fungal, but not E. coli, infection. We determine that Deaf1 acts downstream of the NF-kappa B factors Dorsal and Dif. These results indicate that Deaf1 is an important contributor to innate immune responses in vivo. Copyright (C) 2009 S. Karger AG, Basel
    Type of Publication: Journal article published
    PubMed ID: 20375635
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  • 3
    Keywords: CANCER ; tumor ; carcinoma ; CELL ; Germany ; PATHWAY ; PATHWAYS ; CLASSIFICATION ; FOLLOW-UP ; DISEASE ; TUMORS ; PATIENT ; primary ; renal ; TYPE-1 ; FREQUENCY ; STAGE ; PATTERNS ; DIFFERENCE ; EVOLUTION ; MORPHOLOGY ; CARCINOMAS ; SERIES ; ABNORMALITIES ; TYPE-2 ; CORTICAL TUMORS ; GAINS
    Abstract: We evaluated clinical characteristics, patient outcome (mean follow-up, 47 months), and cytogenetic abnormalities in the largest as yet reported cytogenetic series of 47 primary and 11 secondary papillary renal cell carcinomas for differences between the recently proposed type 1 and type 2 subtypes. Secondary tumors were more often of type 2 morphology (P = 0.02), whereas primary type 2 tumors were associated with higher clinical stage (P = 0.001) and worse patient outcome (P = 0.02). Although both subtypes had at least one of the primary chromosomal gains at 17q, 7, and 16q, type 2 tumors had moderately lower frequencies of primary gains at 17p (61 versus 94%; P = 0.007) and 17q (72 versus 97%; P = 0.02). On the other hand, type 2 tumors overall had more chromosomal alterations than type 1 tumors (P = 0.01), particularly gains of 1q (28 versus 3%; P = 0.02) and losses of 8p (33 versus 0%; P = 0.001), 11 (28 versus 3%; P = 0.02), and 18 (44 versus 9%; P = 0.01). Hierarchical clustering suggested cytogenetic patterns common but not restricted to type 2 morphology, one characterized by multiple additional gains, and another predominantly showing additional losses. These findings provide genetic evidence that type 1 and type 2 tumors arise from common cytogenetic pathways and that type 2 tumors evolve from type 1 tumors. Independently of type, losses of 9p were statistically correlated with advanced disease (P = 0.0008) and may serve as a potential adverse prognostic marker in papillary renal cell carcinomas
    Type of Publication: Journal article published
    PubMed ID: 14559804
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  • 4
    Keywords: CANCER ; CELLS ; EXPRESSION ; SURVIVAL ; tumor ; TUMOR-CELLS ; carcinoma ; Germany ; PATHWAY ; PATHWAYS ; CLASSIFICATION ; DIAGNOSIS ; CDNA ; GENE ; GENE-EXPRESSION ; GENES ; HYBRIDIZATION ; microarray ; TISSUE ; TUMORS ; PATIENT ; kidney ; GROWTH-FACTOR RECEPTOR ; SEQUENCE ; IDENTIFICATION ; PROGRESSION ; MALIGNANCIES ; PATTERNS ; gene expression ; microarrays ; METASTASIS ; ABNORMALITIES ; C-MYC ; MICROARRAY ANALYSIS ; CDNA MICROARRAYS ; CDNA MICROARRAY ; RENAL-CELL CARCINOMA ; molecular ; MALIGNANCY ; RE ; PATIENT SURVIVAL ; SOLID TUMORS ; EXPRESSED SEQUENCE TAGS ; PROTOONCOGENE ; cytogenetic ; CELL-CARCINOMA ; EXPRESSION PATTERNS ; SIGNATURE
    Abstract: Current diagnosis of renal cancer consists of histopathologic examination of tissue sections and classification into tumor stages and grades of malignancy. Until recently, molecular differences between tumor types were largely unknown. To examine such differences, we did gene expression measurements of 112 renal cell carcinoma and normal kidney samples on renal cell carcinoma-specific cDNA microarrays containing 4,207 genes and expressed sequence tags. The gene expression patterns showed deregulation of complete biological pathways in the tumors. Many of the molecular changes corresponded well to the histopathologic tumor types, and a set of 80 genes was sufficient to classify tumors with a very low error rate. Distinct gene expression signatures were associated with chromosomal abnormalities of tumor cells, metastasis. formation, and patient survival. The data highlight the benefit of microarrays to detect novel tumor classes and to identify genes that are associated with patient variables and tumor properties
    Type of Publication: Journal article published
    PubMed ID: 15701852
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  • 5
    Keywords: CELLS ; Germany ; PATHWAY ; PATHWAYS ; SYSTEM ; SYSTEMS ; GENOME ; COMPONENTS ; INTERVENTION ; FLOW ; ASSAY ; FLOW-CYTOMETRY ; CDNAS ; RE ; FULL-LENGTH HUMAN ; ASSAYS ; technique ; RNAi ; BIOCONDUCTOR ; INFERENCE ; SCREENS ; preprocessing
    Abstract: Highthroughput cell-based assays with flow cytometric readout provide a powerful technique for identifying components of biologic pathways and their interactors. Interpretation of these large datasets requires effective computational methods. We present a new approach that includes data pre-processing, visualization, quality assessment, and statistical inference. The software is freely available in the Bioconductor package prada. The method permits analysis of large screens to detect the effects of molecular interventions in cellular systems
    Type of Publication: Journal article published
    PubMed ID: 16916453
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  • 6
    Keywords: CELLS ; PATHWAY ; PROTEIN ; DESIGN ; Drosophila ; DNA-DAMAGE ; CAENORHABDITIS-ELEGANS ; ATR ; CHK1 ; INTERFERENCE ; SCREENS ; RNAi screening ; ART ; DNA damage response signalling ; GENETIC SCREENS ; massively parallel phenotyping ; phenotype networks
    Abstract: Genetic screens for phenotypic similarity have made key contributions to associating genes with biological processes. With RNA interference (RNAi), highly parallel phenotyping of loss-of-function effects in cells has become feasible. One of the current challenges however is the computational categorization of visual phenotypes and the prediction of biological function and processes. In this study, we describe a combined computational and experimental approach to discover novel gene functions and explore functional relationships. We performed a genome-wide RNAi screen in human cells and used quantitative descriptors derived from high-throughput imaging to generate multiparametric phenotypic profiles. We show that profiles predicted functions of genes by phenotypic similarity. Specifically, we examined several candidates including the largely uncharacterized gene DONSON, which shared phenotype similarity with known factors of DNA damage response (DDR) and genomic integrity. Experimental evidence supports that DONSON is a novel centrosomal protein required for DDR signalling and genomic integrity. Multiparametric phenotyping by automated imaging and computational annotation is a powerful method for functional discovery and mapping the landscape of phenotypic responses to cellular perturbations.
    Type of Publication: Journal article published
    PubMed ID: 20531400
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