Genome-Wide Expression Profiles Drive Discovery of Novel Compounds that Reduce Binge Drinking in Mice
Laura B. Ferguson,Angela R. Ozburn,Igor Ponomarev,Pamela Metten,M. E. Reilly,John C. Crabbe,R. Adron Harris,R. Dayne Mayfield +7 more
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TLDR
Terreic acid and pergolide robustly reduced alcohol intake and BALs in HDID-1 mice, providing the first evidence for transcriptome-based drug discovery to target an addiction trait.About:
This article is published in Neuropsychopharmacology.The article was published on 2018-05-01 and is currently open access. It has received 38 citations till now. The article focuses on the topics: Alcohol use disorder & Binge drinking.read more
Citations
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Signature-based approaches for informed drug repurposing: targeting CNS disorders.
Rammohan Shukla,Nicholas D. Henkel,Khaled Alganem,Abdul-Rizaq Hamoud,James Reigle,Rawan Alnafisah,Hunter M. Eby,Ali S Imami,Justin F. Creeden,Scott A. Miruzzi,Jaroslaw Meller,Robert E. McCullumsmith +11 more
TL;DR: Various signature-based in silico approaches to drug repurposing, its integration with multiple omics platforms, and how this data can be used for clinically relevant, evidence-based drugRepurposing are discussed.
Journal ArticleDOI
Chronic Chemogenetic Stimulation of the Nucleus Accumbens Produces Lasting Reductions in Binge Drinking and Ameliorates Alcohol-Related Morphological and Transcriptional Changes.
Dar'ya Y Pozhidayeva,Dar'ya Y Pozhidayeva,Sean P. Farris,Calla Goeke,Evan J. Firsick,Kayla G. Townsley,Marina Guizzetti,Angela R. Ozburn +7 more
TL;DR: It was found that chronic binge drinking altered neuronal morphology in the NAc, an effect that was ameliorated with CNO/hM3Dq, and LMK235, an HDAC4/5 inhibitor, reduced binge-like drinking.
Journal ArticleDOI
Effects of Pharmacologically Targeting Neuroimmune Pathways on Alcohol Drinking in Mice Selectively Bred to Drink to Intoxication.
Angela R. Ozburn,Pamela Metten,Sheena Potretzke,Kayla G. Townsley,Yuri A. Blednov,John C. Crabbe +5 more
TL;DR: A number of compounds shown to reduce ethanol drinking in other models and genotypes are not effective in HDID mice, or their genetically heterogeneous founders, HS/NPT; the most promising compound was the PDE4 inhibitor, rolipram.
Posted ContentDOI
Evaluation of Connectivity Map shows limited reproducibility in drug repositioning
Nathaniel Lim,Paul Pavlidis +1 more
TL;DR: This work used two iterations of CMap to assess their comparability and reliability and attempted to identify the “better” CMap by comparison with a third dataset, but they were mutually discordant.
Journal ArticleDOI
Targeting the Glucocorticoid Receptor Reduces Binge‐Like Drinking in High Drinking in the Dark (HDID‐1) Mice
Antonia Savarese,Angela R. Ozburn,Pamela Metten,Jason P. Schlumbohm,Wyatt R. Hack,Kathryn LeMoine,Hazel Hunt,Felix Hausch,Michael Bauder,John C. Crabbe +9 more
TL;DR: Data suggest that the selection process increased sensitivity to GR antagonism on ethanol intake in the HDID-1 mice, and support a role for the GR as a genetic risk factor for high-risk alcohol intake.
References
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limma powers differential expression analyses for RNA-sequencing and microarray studies
Matthew E. Ritchie,Belinda Phipson,Di Wu,Yifang Hu,Charity W. Law,Wei Shi,Gordon K. Smyth,Gordon K. Smyth +7 more
TL;DR: The philosophy and design of the limma package is reviewed, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
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The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease
Justin Lamb,Emily D. Crawford,David Peck,Joshua W. Modell,Irene C. Blat,Matthew J. Wrobel,Jim Lerner,Jean Philippe Brunet,Aravind Subramanian,Kenneth N. Ross,Michael Reich,Haley Hieronymus,Haley Hieronymus,Guo Wei,Guo Wei,Scott A. Armstrong,Scott A. Armstrong,Stephen J. Haggarty,Stephen J. Haggarty,Paul A. Clemons,Ru Wei,Steven A. Carr,Eric S. Lander,Eric S. Lander,Todd R. Golub +24 more
TL;DR: The first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules is created, and it is demonstrated that this “Connectivity Map” resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs.
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An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex
Ye Zhang,Kenian Chen,Steven A. Sloan,Mariko L. Bennett,Anja R. Scholze,Sean O'Keeffe,Hemali Phatnani,Paolo Guarnieri,Christine Caneda,Nadine Ruderisch,Shuyun Deng,Shane A. Liddelow,Chaolin Zhang,Richard Daneman,Tom Maniatis,Ben A. Barres,Jian Qian Wu +16 more
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A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles.
Aravind Subramanian,Rajiv Narayan,Steven M. Corsello,Steven M. Corsello,David Peck,Ted Natoli,Xiaodong Lu,Joshua Gould,John F. Davis,Andrew A. Tubelli,Jacob K. Asiedu,David L. Lahr,Jodi E. Hirschman,Zihan Liu,Melanie Donahue,Bina Julian,Mariya Khan,David Wadden,Ian Smith,Daniel D. Lam,Arthur Liberzon,Courtney Toder,Mukta Bagul,Marek Orzechowski,Oana M. Enache,Federica Piccioni,Sarah A. Johnson,Nicholas J. Lyons,Alice H. Berger,Alice H. Berger,Alykhan F. Shamji,Angela N. Brooks,Angela N. Brooks,Anita Vrcic,Corey Flynn,Jacqueline Rosains,David Y. Takeda,David Y. Takeda,Roger Hu,Desiree Davison,Justin Lamb,Kristin Ardlie,Larson Hogstrom,Peyton Greenside,Nathanael S. Gray,Nathanael S. Gray,Paul A. Clemons,Serena J. Silver,Xiaoyun Wu,Wen-Ning Zhao,Wen-Ning Zhao,Willis Read-Button,Xiaohua Wu,Stephen J. Haggarty,Stephen J. Haggarty,Lucienne Ronco,Jesse S. Boehm,Stuart L. Schreiber,Stuart L. Schreiber,Stuart L. Schreiber,John G. Doench,Joshua A. Bittker,David E. Root,Bang Wong,Todd R. Golub +64 more
TL;DR: The expanded CMap is reported, made possible by a new, low-cost, high-throughput reduced representation expression profiling method that is shown to be highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts.
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