Dysregulation of NRSF/REST via EHMT1 is associated with psychiatric disorders and Kleefstra syndrome, Z scores
Description:
EHMT1 is an epigenetic repressor that is causal for Kleefstra Syndrome (KS), a neurodevelopmental disorder (NDD) leading to intelectual disability, and is associated with schizophrenia. Here, the researchers aim to show we show that reduced EHMT1 activity decreases NRSF/REST protein leading to abnormal neuronal gene expression and progression of neurodevelopment in human iPSC. Five induced pluripotent stem cell samples (from fibroblasts of adult, male, skin) were used. The stem cells were gifted from: Lieber Institute for Brain Development, Johns Hopkins Medical Campus. Total RNA extracted from a control hiPSC line and control cells treated for 72h with various concentrations of UNC0638 i.e 50, 100, 200 or 250nM as a model for Kleefstra syndrome. Polyadenylated adaptors were ligated to the 3′-end, 5′-adaptors were then ligated, and the resulting RNAs were reverse transcribed to generate cDNA that can be amplified by PCR. The amplified product was run on low range ultra agarose in TBE buffer and a size-selection was performed to ensure that the cDNA used for sequencing primarily contains miRNAs rather than other RNA contaminants. Expression values were calculated by the method detailed in 'HBA-DEALS: accurate and simultaneous identification of differential expression and splicing using hierarchical Bayesian analysis' (Genome Biol. 2020, PMID: 32660516), and Z scores calculated. Genes were annotated as Ensembl gene ids. SRA Study id ERP130338.
Differentially expressed genes from RPE compared to Normal Retina
Description:
Transcriptome profiling from macular retina and RPE/choroid samples from 27 unrelated eye tissue donors, was performed using RNA-sequencing. Human donor eye collection were obtained from Utah Lions Eye Bank within a 6-hour post-mortem interval and donors aged 60-90 years. Sample types were Normal Retina, Intermediate AMD Retina, Neovascular AMD Retina, Normal macular retina pigment epithelium (RPE), Intermediate AMD RPE, and Neovascular AMD RPE. Age Related Macular Degeneration (AMD) phenotyping was determined using the Age-Related Eye Disease Study (AREDS) severity grading scale, where AREDS category 0/1 was considered normal, AREDS category 3 intermediate AMD, and AREDS category 4b neovascular AMD. Samples from Normal RPE were compared to Normal Retina, and are presented with fold change > 1.5 and and P < 0.05. This gene set was annotated from the Supplementry Table of BioRxiv pre-print paper ‘Patterns of gene expression and allele-specific expression vary among macular tissues and clinical stages of Age-related Macular Degeneration’ by Zhang et.al (2022) doi: https://doi.org/10.1101/2022.12.19.521092
Postmortem tissue samples of the dorsolateral prefrontal cortex (DLPFC) from 153 deceased individuals (Mage = 35.4; 62% male; 77% European ancestry). Study groups included 72 brain samples from individuals who died of acute opioid intoxication, 53 psychiatric controls, and 28 normal controls. Whole transcriptome RNA-sequencing was used to generate exon counts, and differential expression was tested using limma-voom. Analyses were adjusted for relevant sociodemographic characteristics, technical covariates, and cryptic relatedness using quality surrogate variables. Weighted correlation network analysis and gene set enrichment analyses also were conducted.
Authors:
David W Sosnowski, Andrew E Jaffe, Ran Tao, Amy Deep-Soboslay, Chang Shu, Sarven Sabunciyan, Joel E Kleinman, Thomas M Hyde, Brion S Maher
Postmortem tissue samples of the dorsolateral prefrontal cortex (DLPFC) from 153 deceased individuals (Mage = 35.4; 62% male; 77% European ancestry). Study groups included 72 brain samples from individuals who died of acute opioid intoxication, 53 psychiatric controls, and 28 normal controls. Whole transcriptome RNA-sequencing was used to generate exon counts, and differential expression was tested using limma-voom. Analyses were adjusted for relevant sociodemographic characteristics, technical covariates, and cryptic relatedness using quality surrogate variables. Weighted correlation network analysis and gene set enrichment analyses also were conducted.
Authors:
David W Sosnowski, Andrew E Jaffe, Ran Tao, Amy Deep-Soboslay, Chang Shu, Sarven Sabunciyan, Joel E Kleinman, Thomas M Hyde, Brion S Maher
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Corradin et al. 2022_log2FC
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Corradin et al. 2022_qvalue
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Mendez et al 2021_log2FC
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Seney et al 2021_log2FC
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Seney et al 2021_qvalue
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Sosnowski et al 2022_log2FC
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Sosnowski et al 2022_qvalue
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Cerebellum Gene Expression Correlates for CONSTRICT measured in BXD RI Females & Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The CONSTRICT measures Morphine Response Severity of abdominal constriction under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Hippocampus Gene Expression Correlates for OF_CENTER_TIME_PCT measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The OF_CENTER_TIME_PCT measures Open Field - Percentage center time under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Hippocampus Gene Expression Correlates for OF_CENTER_TIME_PCT measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The OF_CENTER_TIME_PCT measures Open Field - Percentage center time under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Hippocampus Gene Expression Correlates for OF_TOT_PERIM_TIME_PCT measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The OF_TOT_PERIM_TIME_PCT measures Open Field-Total time in perimeter under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Whole Brain Gene Expression Correlates for ROTAETHA_DIFF measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ROTAETHA_DIFF measures Difference in time on rotarod between training and ethanol under the domain Ethanol. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for OF_REAR_15_20 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The OF_REAR_15_20 measures Open Field - Total rears 15-20 minutes under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for OF_REAR_5_10 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The OF_REAR_5_10 measures Open Field - Total rears 5-10 minutes under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for OF_REARS measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The OF_REARS measures Open Field - Total number of Rears under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Chronic cocaine - Cocaine-paired (conditioned place preference) vs. Control (saline or cocaine-non-paired) DNA microarray All genes on microarray presented After the pre-conditioning phase where animals were allowed access to either compartment for 15 minutes for 4 consecutive days, the conditioning phase for the cocaine-paired groups and cocaine non-paired groups began, consisting of eight subsequent daily sessions. For both groups, cocaine (10 mg / kg) or saline injections were administered on alternate days. For the cocaine-paired groups, rats were immediately placed in one of the two compartments for 30 min with the door in place restricting a z transformation followed by z test and anova followed by Student-Newman-Keuls' post hoc test. Gene expression profile was assessed 24 h after the last conditioning session that corresponded to 48 h after last cocaine exposure, when drug has been eliminated from the body and transient transcriptional changes are likely to be minimal. Therefore, changes in gene expression at this time-point are likely to reflect longer lasting adaptations that may account for maintenance of cocaine-induced memories. The complete lists of normalized gene expression values for the hippocampus of saline-treated, cocaine non-paired and cocaine-paired groups are presented. Analyses revealed that 214 transcripts were differentially regulated in the hippocampus of cocaine-paired rats vs. non-paired and saline-treated controls. Cocaine-induced conditioned place preference caused significant increases in the expression of 151 genes and caused decreases in the expression of 63 genes. (NIF Table ID 130.1 [83])
Authors:
Krasnova IN, Li SM, Wood WH, McCoy MT, Prabhu VV, Becker KG, Katz JL, Cadet JL
Chronic cocaine - Cocaine-paired (conditioned place preference) vs. Control (saline or cocaine-non-paired) DNA microarray All genes on microarray presented After the pre-conditioning phase where animals were allowed access to either compartment for 15 minutes for 4 consecutive days, the conditioning phase for the cocaine-paired groups and cocaine non-paired groups began, consisting of eight subsequent daily sessions. For both groups, cocaine (10 mg / kg) or saline injections were administered on alternate days. For the cocaine-paired groups, rats were immediately placed in one of the two compartments for 30 min with the door in place restricting a z transformation followed by z test and anova followed by Student-Newman-Keuls' post hoc test. Gene expression profile was assessed 24 h after the last conditioning session that corresponded to 48 h after last cocaine exposure, when drug has been eliminated from the body and transient transcriptional changes are likely to be minimal. Therefore, changes in gene expression at this time-point are likely to reflect longer lasting adaptations that may account for maintenance of cocaine-induced memories. The complete lists of normalized gene expression values for the frontal cortex of saline-treated, cocaine non-paired and cocaine-paired groups are presented. Differences in the expression of 39 transcripts in the frontal cortex were related to the conditioned place preference paradigm. These include increases in the level of 22 genes and decreases in 17 genes. (NIF Table ID 130.3 [83.5])
Authors:
Krasnova IN, Li SM, Wood WH, McCoy MT, Prabhu VV, Becker KG, Katz JL, Cadet JL
GeneWeaver