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Integrative genomic strategies applied to a lymphoblast cell line model reveal specific transcriptomic signatures associated with clozapine response [methylation]

ABSTRACT: in vitro genomic analyses of clozapine response. Genome wide DNA methylation profiling was performed across several experimental conditions of clozapine exposure. LCLs were exposed to different concentrations of clozapine (vehicle (DMSO), 1x, 20x, 40x and 60 times clinical concentration) and exposure times were 24h and 96h.

ORGANISM(S): Homo sapiens

PROVIDER: GSE158716 | GEO | 2020/09/30

REPOSITORIES: GEO

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Integrative genomic strategies applied to a lymphoblast cell line model reveal specific transcriptomic signatures associated with clozapine response [expression]

Project description:In vitro genomic analyses of clozapine response. Genome wide gene expression profiling was performed across several experimental conditions of clozapine exposure. LCLs were exposed for 24 hours to 1x, 10x, 50x and 100x clinical concentration (2μM, 20μM,100μM,200 μM clozapine) and vehicle (DMSO); each concentration was measured in 4 cell lines.

2020-10-01 | GSE158819 | GEO

Differential methylation in patients treated with clozapine

Project description:Genome-wide DNA methylation profile of peripheral blood leukocyte samples taken from patients under clozapine treatment. The Infinium MethylationEPIC BeadChip was analyzed to obtain DNA methylation profiles in samples from 31 patients with psychotic disorders under treatment with clozapine and 56 patients with psychiatric disorders naïve to psychopharmacological treatment

2022-02-24 | GSE197136 | GEO

Transcription profiling of mouse brain treated with clozapine and haloperidol

Project description:This SuperSeries is composed of the following subset Series:; GSE6467: Twelve weeks expression data of the antipsychotics Clozapine and Haloperidol in the mouse brain (Affymetrix, GCRMA). GSE6511: Four weeks expression data of the antipsychotics Clozapine and Haloperidol in the mouse brain (Affymetrix, GCRMA). Experiment Overall Design: Refer to individual Series

2008-06-14 | E-GEOD-6512 | biostudies-arrayexpress

Transcription profiling of mouse brain after twelve week treatment with the antipsychotics Clozapine and Haloperidol

Project description:Atypical antipsychotic Clozapine has a superior antipsychotic and antimanic effects compared to other antisphicotics. Its widespread use was limited by the side effects of agranulocytosis, cardiomyopathy and metabolic anomalies such as weight gain, and diabetes. Very little is known about mechanisms by which Clozapine works. The aim of this experiment is to compare the chronic gene expression profile of the atypical antipsychotic Clozapine to the typical antipsychotic drug Haloperidol using gene expression Microarray in order to understand the intercellular mechanism behind the therapeutic and the toxic effects of Clozapine. Experiment Overall Design: The study was designed to compare the chronic therapeutic and toxic expression profile of Clozapine to Haloperidol in the mouse brain. All experiments were performed in male C57BL mice at four weeks of age (Biological services, University Collage London). Several theoretical and practical considerations influenced the final experimental design. To avoid the effect of injections on genes expression and to simulate the clinical scenario in human, both drugs were applied to the animals drinking water using the maximum human therapeutic dose (i.e. 1.6mg/kg/day for Haloperidol and 12mg/kg/day for Clozapine). Thirty animals were divided equally between three treatment groups and received either Haloperidol (10 animals), Clozapine (10 animals) or no treatment (10 animals) for 12 weeks. After twelve weeks, the total RNA from the right forebrains were extracted and hybridized to the Affymetrix MOE430A array. In all the Microarray experiments we have avoided pooling and each RNA sample was an independent biological replicate. The total numbers of used arrays were 30 Affymetrix MOE430A arrays.

2009-02-07 | E-GEOD-6467 | biostudies-arrayexpress

Twelve weeks expression data of the antipsychotics Clozapine and Haloperidol in the mouse brain (Affymetrix, GCRMA).

2006-12-13 | GSE6467 | GEO

Four weeks expression data of the antipsychotics Clozapine and Haloperidol in the mouse brain (Affymetrix, GCRMA).

2006-12-13 | GSE6511 | GEO

Transcription profiling of mouse brain from animals treated for 4 weeks with the antipsychotics Clozapine and Haloperidol

Project description:Atypical antipsychotic Clozapine has a superior antipsychotic and antimanic effects compared to other antisphicotics. Its widespread use was limited by the side effects of agranulocytosis, cardiomyopathy and metabolic anomalies such as weight gain, and diabetes. Very little is known about mechanisms by which Clozapine works. The aim of this experiment is to compare the chronic gene expression profile (i.e four weeks) of the atypical antipsychotic Clozapine to the typical antipsychotic drug Haloperidol using gene expression Microarray in order to understand the intercellular mechanism behind the therapeutic and the toxic effects of Clozapine. Experiment Overall Design: The study was designed to compare the chronic therapeutic and toxic expression profile of Clozapine to Haloperidol in the mouse brain. All experiments were performed in male C57BL mice at four weeks of age (Biological services, University Collage London). Several theoretical and practical considerations influenced the final experimental design. To avoid the effect of injections on genesâ expression and to simulate the clinical scenario in human, both drugs were applied to the animalsâ drinking water using the maximum human therapeutic dose (i.e.1.6mg/kg/day for Haloperidol and 12mg/kg/day for Clozapine).Thirty animals were divided equally between three treatment groups and received either Haloperidol (10 animals), Clozapine (10 animals) or no treatment (10 animals) for 4 weeks. After four weeks,the plasma drug level for both drugs was assesed by Tandem mass Spectrometry LC- MS/MS. The total RNA from the right forebrains of nine selected animals (three from each treatment group) were extracted and hybridized to the Affymetrix U74Av2. In all the Microarray experiments we have avoided pooling and each RNA sample was an independent biological replicate. The total numbers of used arrays were 9 Affymetrix U74Av2.

2009-04-30 | E-GEOD-6511 | biostudies-arrayexpress

Integrative genomic strategies applied to a lymphoblast cell line model reveal specific transcriptomic signatures associated with clozapine response

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-10-01 | GSE158821 | GEO

Toxicoproteomics reveals an effect of Clozapine on autophagy in human liver spheroids

Project description:Clozapine is an atypical antipsychotic drug used to treat treatment-resistant schizophrenia. Its side effects, including liver enzyme abnormalities, experienced by many patients preclude its more common use as a first-line therapy for schizophrenia. Toxicoproteomic approaches have been demonstrated to effectively guide the identification of toxicological mechanisms. Here, to further our understanding of the molecular effects of clozapine, we performed a data-independent acquisition (DIA)-based quantitative proteomics investigation of clozapine-treated human liver spheroid cultures. In total, we quantified 4,479 proteins across the five treatment groups (vehicle; 15 µM, 30 µM, and 60 µM clozapine; and 10 ng/mL TNFα + IL-1β). Clozapine (60 µM) treatment yielded 36 differentially expressed proteins (FDR < 0.05). Gene-set enrichment analysis indicated perturbation of several gene sets, including interferon gamma signaling (e.g., interferon gamma receptor 1) and prominent autophagy-related processes (e.g., upregulation of sequestosome-1 (SQSTM1), MAP1LC3B/LC3B2, GABARAPL2, and nuclear receptor coactivator 4). The effects of clozapine on autophagy were confirmed by targeted mass spectrometry and western blotting using conventional SQSTM1 and LC3B markers. Combined with prior literature, our work suggests a broad contribution of autophagy to both the therapeutic and side effects of clozapine. Overall, this study demonstrates how proteomics can contribute to the elucidation of physiological and toxicological mechanisms of drugs.

2022-12-13 | PXD038007 | Pride

Integrative genomic strategies applied to a lymphoblast cell line model reveal specific transcriptomic signatures associated with clozapine response

Project description:Integrative genomic strategies applied to a lymphoblast cell line model reveal specific transcriptomic signatures associated with clozapine response

| PRJNA666646 | ENA

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