MARC contact VIDAL

..Identifying shared and distinct host-pathogen protein interaction profiles for these two viruses would enlighten how they exploit distinctive or common strategies to subvert cellular pathways toward disease progression...

..Several regions containing disease-causing mutations or cancer polymorphisms in human are predicted to be binding for protein pairs related to the disease, which suggests novel mechanistic hypotheses for several diseases...

..Here we describe a powerful strategy, Micro-Array Profiling of C. elegans cells (MAPCeL), and confirm that this approach provides a comprehensive gene expression profile of unc-4::GFP motor neurons in vivo...

..elegans transcription factor genes was examined, in vivo, with a reporter gene approach...

..For instance, lin-35 Rb is a synthetic multivulva (synMuv) class B gene, which causes a multivulva phenotype when inactivated simultaneously with a class A or C synMuv gene...

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..This review focuses on an early attempt at mapping a multicellular interactome network and on the lessons learned from that attempt...

..elegans ORFeome, and likely the ORFeomes of other multicellular organisms, needs to be an iterative process that requires multiple rounds of experimental validation together with gradually improving gene predictions...

..We suggest that similar ORFeome projects will be valuable for other organisms, including humans...

..Topological and biological features of this interactome network, as well as its integration with phenome and transcriptome data sets, lead to numerous biological hypotheses...

..Thus, the combination of functional genomic mapping approaches in model organisms may facilitate the identification and characterization of genes involved in cancer and, perhaps, other human diseases...

..dfci.harvard.edu). This expansion of the original ORFeome resource greatly increases the potential experimental search space for large-scale proteomics studies, which will lead to the generation of more comprehensive datasets...

..Our network modeling strategy should be useful for the discovery of additional cancer-associated genes...

..We demonstrate that some of these genes are also required for germline and somatic transgene silencing. Moreover, the physical interactions among these potential RNAi factors suggest links to other RNA-dependent gene regulatory pathways...

..Rather than correlating with essentiality, protein connectivity correlates with genetic pleiotropy...

..Contaminating plasmids are eliminated by extended culture of yeast cells under positive selection for the interaction, allowing the identification of the true interaction partner...

..This approach is amenable to higher throughput and is particularly applicable to interactome network analysis in organisms for which transgenesis is straightforward...

..Integrating interactome maps with systematic genetic perturbations may be useful for developing a systems biology approach to this and other signaling modules...

..We conclude that given the current limited coverage levels, the observed scale-free topology of existing interactome maps cannot be confidently extrapolated to complete interactomes...

..Such maps are also a useful resource to predict the function(s) of thousands of genes...

..This work represents an important step towards a systematic and comprehensive human interactome project...

..Our results show that as much as 20% of the C. elegans genome may be incorrectly annotated. Many annotation errors could be corrected proactively with our large-scale RACE platform...

..Multimodal analyses like ours could advance understanding of tumor suppression by BRCA1 and ultimately contribute to developing efficient strategies for screening and characterization of VUS...

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..In an evaluation of existing curation of protein interaction experiments reported in the literature, we found that curation can be error-prone and possibly of lower quality than commonly assumed...

..This ORFeome discovery pipeline will be applicable to any eukaryotic species with a sequenced genome...

..1 represents a central resource for the cloning of large sets of human ORFs in various settings for functional proteomics of many types, and will serve as the foundation for subsequent improved versions of the human ORFeome...

..Here, we review the recent development of strategies for such integration and we argue that these will be important for a systems approach to modular biology...

..Similar integration of interactome, phenome, and transcriptome data should be possible for other biological processes in the nematode and for other organisms, including humans...

..The database contains this OST information along with data pertinent to the cloning process. WorfDB could serve as a model database for other metazoan ORFeome cloning projects...

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..The versatility inherent to the Gateway system suggests that additional HT-RNAi libraries can now be readily generated to perform gene knockdowns under various conditions, increasing the possibilities for phenome mapping in C. elegans...

..Comparison with other types of functional genomic data shows the complementarity of distinct experimental approaches in predicting different functional relationships between genes or proteins..

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..We suggest that the direct interaction of Dvl2 with AP-2 is important for Frizzled internalization and Frizzled/PCP signaling...

..This interactome modeling strategy revealed insights into C. elegans centrosome function and is applicable to other biological processes in this and other organisms...

..Moreover, integration of this data set with C. elegans protein-protein interactome data sets enables prediction of anatomical and temporal interaction territories between protein partners...

..These observations suggest a mechanism for NF-kappaB activation in breast cancer, implicate the NF-kappaB pathway as a downstream mediator of PI3K, and provide a framework for integrated genomic approaches in oncogene discovery...

..Significant differences in distance were found between etiological and palliative drugs. A recent trend toward more rational drug design was observed...

..The creation of such ORFeome resources using novel technologies for cloning and expressing entire proteomes constitutes an effective gateway from whole genome sequencing efforts to downstream 'omics' applications...

..Static graphs currently used to model Y2H and AP-MS data neglect dynamic and spatial aspects of macromolecular complexes and pleiotropic protein function...

..This general approach will allow a systematic and empirical assignment of confidence scores to all individual protein-protein interactions in interactome networks...

..Rather, such ORFs might be important for micro-evolutionary divergence between species...

..Twenty-four genes encoded proteins that were localized to presynaptic specializations. Loss-of-function mutations in 12 genes caused defects in presynaptic structure...

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..Our results have important implications for understanding CI function and pathogenesis and, more generally, illustrate how our compendium can serve as a foundation for systematic investigations of mitochondria...

..Mutational analysis reveals that FAST-mediated alternative splicing is separable from the survival effects of FAST. Our data reveal that nuclear FAST can regulate the splicing of FGFR2 transcripts...

..The resulting resource of prioritized associations between Drosophila genes and their potential functions offers a guide for experimental investigations...

..Targeting of hubs might be an efficient mechanism for EBV reorganization of cellular processes...

..Edgetic network perturbation models might improve both the understanding of dissemination of disease alleles in human populations and the development of molecular therapeutic strategies...

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..Our findings support a shared role for Ce-BRC-1 and Ce-BRD-1 in C. elegans DNA repair processes, and this role will permit studies of the BRCA1 pathway in an organism amenable to rapid genetic and biochemical analysis...

..elegans CUL-3. Biochemical studies using the BTB protein MEL-26 and its genetic target MEI-1 (refs 12, 13) indicate that BTB proteins merge the functional properties of Skp1 and F-box proteins into a single polypeptide...

..However, in metazoans, DNA damage can induce apoptosis as well. How DNA damage activates the apoptotic machinery is not fully understood...

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..Furthermore, we discovered a striking direct relationship between phylogenetic distribution and the penetrance level of embryonic lethality elicited by RNAi...

..We assessed the overall predictive value of such molecular machine models by dynamic localization of ten previously uncharacterized proteins within the living embryo...

..Using POET, pools of ORFs can be constructed, and the pools of the resulting proteins can be analyzed and manipulated to rapidly acquire information about the attributes of hundreds of proteins simultaneously...

..The pipeline described here is applicable to high-throughput expression of recombinant proteins for other species, both prokaryotic and eukaryotic, provided that ORFeome resources become available...

..Taken together, the Gateway-compatible Y1H system will allow the high-throughput identification of protein-DNA interactions and may be a valuable tool to decipher transcription regulatory networks...

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..This interactome thus provides a tool for understanding pathogenic mechanisms common for this class of neurodegenerative disorders and for identifying candidate genes for inherited ataxias...

..The results of this study demonstrate that intrinsic structural disorder is a distinctive and common characteristic of eukaryotic hub proteins, and that disorder may serve as a determinant of protein interactivity...

..The results also suggest that this technology can significantly improve our knowledge of the "parts list" for even the best-studied model organisms...

..elegans germline and functions as a negative regulator of the MAPK signaling pathway during vulval development and in muscle cells...

..The recombinational cloning involved in the Gateway system, which permits the highly efficient and precise transfer of DNA segments between plasmid vectors, makes this technology ideal for genomics research programs...

..Here we discuss the use of a recombinational cloning system that allows efficiency, adaptability, and compatibility in the generation of ORFeome, promoterome, and other resources...

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..We test a number of these in two-hybrid experiments and are able to verify 45 overlaps, which we show to be statistically significant...

..We propose that MEX-6 and SPN-4 act with MEX-3 to translate the temporal and spatial information provided by the early acting par genes into the asymmetric expression of the cell fate determinant PAL-1...

..These results define a role for the SWI/SNF complexes in the regulation of lipid homeostasis...

..The ZipTip purified proteins can be further analyzed under both native and denaturing conditions for functional proteomics efforts...

..This work should help in developing the tools and the strategies needed to generate and interpret a comprehensive human-protein interaction database. ..

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..Our modified specific aims are to: i) Provide an expanded high-confidence/high-coverage version of the human binary interactome map ii) Validate human binary interaction data iii) Analyze the expanded human interactome model ..

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..Using a complete set of worm promoters, we then propose to develop high-throughput methods to localize gene expression in vivo and initiate a protein-DNA interaction mapping project (R33). ..

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..Our modified specific aims are to: i) Provide an expanded high-confidence/high-coverage version of the human binary interactome map ii) Validate human binary interaction data iii) Analyze the expanded human interactome model ..