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S.15.01 Data mining and neuroinformatics
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S.15. Integration of large neuroscience data set: a tool for discovery for brain disorders
References [1] O’Callaghan, M.J., Croft, A.P., Jacquot, C., and Little, H.J. (2005) The hypothalamopituitary-adrenal axis and alcohol preference. Brain Res Bull., 68, 165–172. [2] Mulholland, P.J. Self R.L., Harris B.R., Little H.J., Littleton J.M., and Prendergast M.A. (2005) Corticosterone increases damage and cytosolic calcium accumulation associated with ethanol withdrawal in rat hippocampal slice cultures. Alc Clin Exp Res., 29, 453–464. [3] Little, H.J, Croft, A.P, O’Callaghan, M.J., Brooks, S.P., Wang G and Shaw S.G. (2008) Selective increases in regional brain glucocorticoid; a novel effect of chronic alcohol. Neuroscience, 156, 1017–1027.
S.14.05 Place for baclofen in treating alcoholism G. Colombo1 ° , P. Maccioni1 , M.A.M. Carai1 , G.L. Gessa1 . 1 CNR Neuroscience Institute, Cagliari, Italy Accumulating lines of experimental and clinical evidence suggest that the GABAB receptor agonist, baclofen, may represent a novel, promising, and effective pharmacotherapy for alcohol dependence. It has indeed been reported that acutely or repeatedly administered baclofen suppressed several alcohol-related behaviors in rodents, including: (a) acquisition and maintenance of alcohol drinking behavior, relapse-like drinking, binge-like drinking, and cannabinoid- or opioid-induced increase in alcohol intake in rats and mice exposed to the 2-bottle “alcohol vs water” choice regimen; (b) operant, oral alcohol self-administration in rats and mice exposed to the fixed ratio and the progressive ratio schedules of reinforcement; (c) alcohol-seeking behavior in rats exposed to extinction responding procedures; (d) reinstatement of alcoholseeking behavior triggered in rats by the uncontingent presentation of pharmacologically irrelevant amounts of alcohol; (e) alcoholinduced conditioned place preference in mice; (f) alcohol-induced locomotor hyperactivity in mice [1]. Most of the above data were replicated by baclofen infusion into the ventral tegmental area of rats and mice, providing initial clues on the likely involvement of the mesolimbic dopamine system. Finally, baclofen administration has been found to suppress the intensity of different signs of alcohol withdrawal syndrome − including anxiety-related behaviors, tremors, and seizures − in rats made physically dependent on alcohol. Of interest, preliminary clinical surveys and accumulating case-reports extended to human alcoholics most of the above rodent results, as baclofen has been found to promote abstinence and suppress alcohol consumption, craving for alcohol, and severity of alcohol withdrawal symptoms and signs, including delirium tremens, in alcohol-dependent patients [2]. References [1] Maccioni, P., Colombo, G., 2009 Role of the GABAB receptor in alcohol seeking and drinking behavior. Alcohol 43, 555–558. [2] Leggio, L., Garbutt, J.C., Addolorato, G. 2010 Effectiveness and safety of baclofen in the treatment of alcohol dependent patients. CNS Neurol. Disord. Drug Targets, in press.
S.15. Integration of large neuroscience data set: a tool for discovery for brain disorders S.15.01 Data mining and neuroinformatics F.A. Nielsen1 ° . 1 Technical University of Denmark, DTU Informatics, Kongens Lyngby, Denmark Neuroscience publishes an overwhelming number of studies, − and often inconsistent. With aggregation of publications in databases,
deep annotation and representation of result data neuroinformatics methods can improve information retrieval and data mining methods may give quantative indications on consensus and divergence across the many studies. The neuroinformatics databases BrainMap, AMAT and SumsDB as well as our own Brede Database and Brede Wiki curate data from published neuroimaging studies with different degrees of annotation. The Brede tools incorporate taxonomies for brain regions, topics and brain functions to support the annotation. With these databases researchers can search for reported brain coordinates and extract data for meta-analysis. With the Brede tools researchers can make queries to the database from within the SPM neuroimaging analysis program across the Web searching for nearby brain coordinates or similar experiments. In the Brede tools brain coordinates can also be combined with the taxonomies for mass meta-analytic data mining [1]. The major bottleneck in large-scale integration of data sets for meta-analytic data mining is data entry: Neuroinformatics databases cannot keep up with the generated results [2]. Collaborative-based approached may help with this issue. To explore a more collaborative approach for data entry and mining I have setup an online fielded wiki for storing result data from personality genetics. It features an interactive interface where a user can perform meta-analysis and meta-analytic plotting on-thefly as data are entered. The wiki can also export the close to 1000 personality trait scores presently available. Disclosure statement: This paper is financially supported by the Lundbeck Foundation through Center for Integrated Molecular Brain Imaging. References ˚ 2009 Visualizing data mining results with the Brede tools. [1] Nielsen F.A., Frontiers in Neuroinformatics 3, 26. [2] Derrfuss J., Mar R. A., 2009 Lost in localization: The need for a universal coordinate database. NeuroImage 48, 1−7.
S.15.02 Modulation of dysregulated protein-proteininteractions in Huntington’s disease E.E. Wanker1 ° , M. Str¨odicke1 . 1 Max Delbr¨uck Center for Molecular Medicine (MDC) Berlin-Buch, Neuroproteomics, Berlin, Germany Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. The main objective of our work is to understand the cell’s functional organization and to link individual proteins to signalling cascades and disease processes. Therefore, we have developed technologies such as an automated yeast two-hybrid (Y2H) system, which allow the efficient identification of human protein-protein interactions (PPIs). Using these methods we have generated various interaction networks for neurodegenerative diseases and signalling cascades [1,2]. Recently, we have started to integrate data from protein interaction and gene expression studies to predict tissue-specific huntingtin (HTT) interactions that are altered in Huntington’s disease (HD) brains. Applying a method termed INFIDEX (interaction network filtering by differentially expressed genes), a diseaserelevant, brain-specific PPI network was created, linking 14 potentially dysregulated proteins directly or indirectly to HTT. Analysis of previously published data confirmed the predictive value of this unbiased network modeling strategy. One of the identified proteins that directly associate with HTT is the neuron-specific CRMP1 (collapsin response mediator protein 1), which we predicted to be
S.15. Integration of large neuroscience data set: a tool for discovery for brain disorders
References [1] O’Callaghan, M.J., Croft, A.P., Jacquot, C., and Little, H.J. (2005) The hypothalamopituitary-adrenal axis and alcohol preference. Brain Res Bull., 68, 165–172. [2] Mulholland, P.J. Self R.L., Harris B.R., Little H.J., Littleton J.M., and Prendergast M.A. (2005) Corticosterone increases damage and cytosolic calcium accumulation associated with ethanol withdrawal in rat hippocampal slice cultures. Alc Clin Exp Res., 29, 453–464. [3] Little, H.J, Croft, A.P, O’Callaghan, M.J., Brooks, S.P., Wang G and Shaw S.G. (2008) Selective increases in regional brain glucocorticoid; a novel effect of chronic alcohol. Neuroscience, 156, 1017–1027.
S.14.05 Place for baclofen in treating alcoholism G. Colombo1 ° , P. Maccioni1 , M.A.M. Carai1 , G.L. Gessa1 . 1 CNR Neuroscience Institute, Cagliari, Italy Accumulating lines of experimental and clinical evidence suggest that the GABAB receptor agonist, baclofen, may represent a novel, promising, and effective pharmacotherapy for alcohol dependence. It has indeed been reported that acutely or repeatedly administered baclofen suppressed several alcohol-related behaviors in rodents, including: (a) acquisition and maintenance of alcohol drinking behavior, relapse-like drinking, binge-like drinking, and cannabinoid- or opioid-induced increase in alcohol intake in rats and mice exposed to the 2-bottle “alcohol vs water” choice regimen; (b) operant, oral alcohol self-administration in rats and mice exposed to the fixed ratio and the progressive ratio schedules of reinforcement; (c) alcohol-seeking behavior in rats exposed to extinction responding procedures; (d) reinstatement of alcoholseeking behavior triggered in rats by the uncontingent presentation of pharmacologically irrelevant amounts of alcohol; (e) alcoholinduced conditioned place preference in mice; (f) alcohol-induced locomotor hyperactivity in mice [1]. Most of the above data were replicated by baclofen infusion into the ventral tegmental area of rats and mice, providing initial clues on the likely involvement of the mesolimbic dopamine system. Finally, baclofen administration has been found to suppress the intensity of different signs of alcohol withdrawal syndrome − including anxiety-related behaviors, tremors, and seizures − in rats made physically dependent on alcohol. Of interest, preliminary clinical surveys and accumulating case-reports extended to human alcoholics most of the above rodent results, as baclofen has been found to promote abstinence and suppress alcohol consumption, craving for alcohol, and severity of alcohol withdrawal symptoms and signs, including delirium tremens, in alcohol-dependent patients [2]. References [1] Maccioni, P., Colombo, G., 2009 Role of the GABAB receptor in alcohol seeking and drinking behavior. Alcohol 43, 555–558. [2] Leggio, L., Garbutt, J.C., Addolorato, G. 2010 Effectiveness and safety of baclofen in the treatment of alcohol dependent patients. CNS Neurol. Disord. Drug Targets, in press.
S.15. Integration of large neuroscience data set: a tool for discovery for brain disorders S.15.01 Data mining and neuroinformatics F.A. Nielsen1 ° . 1 Technical University of Denmark, DTU Informatics, Kongens Lyngby, Denmark Neuroscience publishes an overwhelming number of studies, − and often inconsistent. With aggregation of publications in databases,
deep annotation and representation of result data neuroinformatics methods can improve information retrieval and data mining methods may give quantative indications on consensus and divergence across the many studies. The neuroinformatics databases BrainMap, AMAT and SumsDB as well as our own Brede Database and Brede Wiki curate data from published neuroimaging studies with different degrees of annotation. The Brede tools incorporate taxonomies for brain regions, topics and brain functions to support the annotation. With these databases researchers can search for reported brain coordinates and extract data for meta-analysis. With the Brede tools researchers can make queries to the database from within the SPM neuroimaging analysis program across the Web searching for nearby brain coordinates or similar experiments. In the Brede tools brain coordinates can also be combined with the taxonomies for mass meta-analytic data mining [1]. The major bottleneck in large-scale integration of data sets for meta-analytic data mining is data entry: Neuroinformatics databases cannot keep up with the generated results [2]. Collaborative-based approached may help with this issue. To explore a more collaborative approach for data entry and mining I have setup an online fielded wiki for storing result data from personality genetics. It features an interactive interface where a user can perform meta-analysis and meta-analytic plotting on-thefly as data are entered. The wiki can also export the close to 1000 personality trait scores presently available. Disclosure statement: This paper is financially supported by the Lundbeck Foundation through Center for Integrated Molecular Brain Imaging. References ˚ 2009 Visualizing data mining results with the Brede tools. [1] Nielsen F.A., Frontiers in Neuroinformatics 3, 26. [2] Derrfuss J., Mar R. A., 2009 Lost in localization: The need for a universal coordinate database. NeuroImage 48, 1−7.
S.15.02 Modulation of dysregulated protein-proteininteractions in Huntington’s disease E.E. Wanker1 ° , M. Str¨odicke1 . 1 Max Delbr¨uck Center for Molecular Medicine (MDC) Berlin-Buch, Neuroproteomics, Berlin, Germany Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. The main objective of our work is to understand the cell’s functional organization and to link individual proteins to signalling cascades and disease processes. Therefore, we have developed technologies such as an automated yeast two-hybrid (Y2H) system, which allow the efficient identification of human protein-protein interactions (PPIs). Using these methods we have generated various interaction networks for neurodegenerative diseases and signalling cascades [1,2]. Recently, we have started to integrate data from protein interaction and gene expression studies to predict tissue-specific huntingtin (HTT) interactions that are altered in Huntington’s disease (HD) brains. Applying a method termed INFIDEX (interaction network filtering by differentially expressed genes), a diseaserelevant, brain-specific PPI network was created, linking 14 potentially dysregulated proteins directly or indirectly to HTT. Analysis of previously published data confirmed the predictive value of this unbiased network modeling strategy. One of the identified proteins that directly associate with HTT is the neuron-specific CRMP1 (collapsin response mediator protein 1), which we predicted to be