Dysregulated immune system networks in war veterans with Post-Traumatic Stress Disorder (PTSD) is an outcome of altered miRNA expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Mitzi Nagarkatti
PROVIDER: E-MTAB-4880 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Purpose: RNA-Seq analysis can help identify large set of differentially expressed genes at a time. We performed RNA-Seq analysis to identify differentially expressed genes in the PBMCs of war veterans suffering from PTSD. Methods: Total RNA from PBMCs from PTSD +ve and -ve individuals were used for RNA-Seq analysis. Results: We obtained, on average, ~60 millions reads per sample. More than 70% of the reads were mapped to human genome. Functional analysis of the differentially expressed genes (362) revealed dysregulation in immune system network. Conclusions: Our present study provides further proof that immune system related genes and pathways are dysregulated in PTSD PBMCs.
2016-08-26 | GSE83601 | GEO
Project description:Dysregulated immune system networks in war veterans with PTSD
| PRJNA326471 | ENA
Project description:Objective: Posttraumatic stress disorder (PTSD) affects a high proportion of returning combat veterans, but the biological mechanisms of PTSD remain unclear. Circulating micro RNAs (miRNAs) have been associated with depression, and anxiety disorders, but there is little understanding of how miRNAs may relate to PTSD. In this study we compare profiles of circulating miRNA in combat veterans with and without PTSD in order to better understand biological mechanisms of PTSD. Methods: Blood from 24 male military service members was collected following deployment to Operation Iraqi Freedom (OIF) or Operation Enduring Freedom (OEF), and subjects were assessed for PTSD symptoms using the PTSD checklist-military version. miRNA was isolated from whole blood and sequenced on the Ion Torrent PGM™ using the Ion 316 Chip v2. Differences in miRNA expression was compared between subjects with PTSD (N=15) and combat matched controls without PTSD (N=9). Significantly different miRNA, according to a FDR≤0.05, were assessed for predictive putative targets, and pathway analysis of related targets was completed. Results: PTSD was associated with 4 upregulated and 4 downregulated miRNA, including a 2.94 fold increase in miR-19a-3p and a 1.56 fold decrease in miR-15b. Pathway analysis show that PTSD is related to the axon guidance and Wnt signaling pathways, which work together along with the adherens junction and MAPK signaling pathways to support neuronal development through regulation of growth cones. The PTSD associated miRNAs related to transcription factors, including Transcription factor 7 (T-cell specific, HMG-box), Transcription factor 7 like 1, and Transcription factor 7 like 2. Conclusions: PTSD is associated with miRNAs that regulate biological functions that include neuronal activities, suggesting that they play a role in PTSD symptomatology.
2017-03-07 | GSE87768 | GEO
Project description:This pilot study enrolled 9 GWI (Gulf War Illness) cases identified from the Department of Veterans Affairs GWI registry, and 11 sedentary control veterans who had not been deployed to the Persian Gulf and were matched to cases by sex, body mass index (BMI) and age.<br>We exposed GWI patients and matched controls to an exercise challenge to explore differences in immune cell function measured by classic immune assays and gene expression profiling.
2009-02-24 | E-MEXP-2069 | biostudies-arrayexpress
Project description:Emerging knowledge suggests that post-traumatic stress disorder (PTSD) is causally associated with epigenetic changes although its molecular underpinnings are still largely elusive. We postulate that differentially methylated probes mined from peripheral whole blood could be candidates for potential PTSD diagnostic signatures. Working within the Systems Biology PTSD Biomarker Consortium (SBPBC), we investigated a training set comprising of 48 PTSD male veterans (CAPS > 40) and 51 age/ethnicity matched controls (CAPS < 20). Agilent whole genome array detected ~5,600 differentially methylated CpG islands (CpGI) annotated to ~2,800 differentially methylated genes (DMG). The majority (84.5%) of these DMGs was hypermethylated in PTSD veterans. Thereof ~30% promoter-bound DMGs were used for functional analysis. Taking cues from the clinical information, the curated networks were enlisted into four major clusters, namely PTSD-associated complications, PTSD-relevant endocrine signaling, nervous system development and nervous system functions. Enduring impacts of PTSD was manifested by differentially methylated genes enriching networks associated with LTP, fear memory architecture and complications linked to insulin resistance and innate immunity. These networks were further validated by an independent test set comprising of 31/29 PTSD+/- veteran selected using aforementioned screening protocol. Two independent assay platforms presented technical validations. Probing the combined 83/83 PTSD+/- cohort, whole genome array from Illumina, Inc. validated most of the networks of interest. Methylation statuses of eight DMGs relevant to PTSD and comorbidities were confirmed by targeted bisulfite sequencing. This list presents a potential set of PTSD biomarkers of translational potential.
2017-07-31 | GSE85399 | GEO
Project description:Emerging knowledge suggests that post-traumatic stress disorder (PTSD) is causally associated with epigenetic changes although its molecular underpinnings are still largely elusive. We postulate that differentially methylated probes mined from peripheral whole blood could be candidates for potential PTSD diagnostic signatures. Working within the Systems Biology PTSD Biomarker Consortium (SBPBC), we investigated a training set comprising of 48 PTSD male veterans (CAPS > 40) and 51 age/ethnicity matched controls (CAPS < 20). Agilent whole genome array detected ~5,600 differentially methylated CpG islands (CpGI) annotated to ~2,800 differentially methylated genes (DMG). The majority (84.5%) of these DMGs was hypermethylated in PTSD veterans. Thereof ~30% promoter-bound DMGs were used for functional analysis. Taking cues from the clinical information, the curated networks were enlisted into four major clusters, namely PTSD-associated complications, PTSD-relevant endocrine signaling, nervous system development and nervous system functions. Enduring impacts of PTSD was manifested by differentially methylated genes enriching networks associated with LTP, fear memory architecture and complications linked to insulin resistance and innate immunity. These networks were further validated by an independent test set comprising of 31/29 PTSD+/- veteran selected using aforementioned screening protocol. Two independent assay platforms presented technical validations. Probing the combined 83/83 PTSD+/- cohort, whole genome array from Illumina, Inc. validated most of the networks of interest. Methylation statuses of eight DMGs relevant to PTSD and comorbidities were confirmed by targeted bisulfite sequencing. This list presents a potential set of PTSD biomarkers of translational potential.
2019-09-01 | GSE89218 | GEO
Project description:Emerging knowledge suggests that post-traumatic stress disorder (PTSD) is causally associated with epigenetic changes although its molecular underpinnings are still largely elusive. We postulate that differentially methylated probes mined from peripheral whole blood could be candidates for potential PTSD diagnostic signatures. Working within the Systems Biology PTSD Biomarker Consortium (SBPBC), we compared 52 PTSD male veterans (CAPS > 40) and 52 age/ethnicity matched controls (CAPS < 20) and detected ~5,600 differentially methylated CpG islands (CpGI) annotated to ~2,800 differentially methylated genes (DMG). The majority (84.5%) of these DMGs was hypermethylated in PTSD veterans, and nearly 30% of those representing the focus group of the present study were differentially methylated in their promoter regions. These promoter-bound DMGs were significantly enriched in four major network-clusters comprising PTSD-associated complications, PTSD-relevant endocrine signaling, nervous system development and nervous system functions. The severity of some current PTSD symptoms was correlated with the increased risk of medical problems, which was captured in epigenetically perturbed networks associated with insulin resistance, circadian rhythm, innate immunity and telomere management. DMGs involved with addiction, fear sensitization and neurotransmissions were enriched in the networks of long term potentiation, depression and fear memory consolidation, and thereby potentially induced lasting impacts on brain. Finally, we curated a set of DMGs that co-enrich multiple PTSD-relevant networks, and we speculate that these genes are cooperative associated with PTSD risk. The present study emphasizes the need to validate these potential PTSD signatures by probing independent cross-sectional and prospective human cohorts.
2017-08-31 | GSE76401 | GEO
Project description:Post-traumatic stress disorder (PTSD) can develop following severe trauma, but the extent to which genetic and environmental risk factors contribute to individual clinical outcomes is unknown. Here, we compared transcriptional responses to hydrocortisone exposure in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons and peripheral blood mononuclear cells (PBMCs) from combat veterans with PTSD (n = 19 hiPSC and n = 20 PBMC donors) and controls (n = 20 hiPSC and n = 20 PBMC donors). In neurons only, we observed diagnosis-specific glucocorticoid-induced changes in gene expression corresponding with PTSD-specific transcriptomic patterns found in human postmortem brains. We observed glucocorticoid hypersensitivity in PTSD neurons, and identified genes that contribute to this PTSD-dependent glucocorticoid response. We find evidence of a coregulated network of transcription factors that mediates glucocorticoid hyper-responsivity in PTSD. These findings suggest that induced neurons represent a platform for examining the molecular mechanisms underlying PTSD, identifying biomarkers of stress response, and conducting drug screening to identify new therapeutics.
2022-11-07 | GSE217320 | GEO
Project description:Analysis of transcript abundance estimates as a function of child soldier status, PTSD symptoms, and psychological resilience. Gene expression profiling was conducted on dried blood spot (DBS) samples collected from community dwelling adolescents and young adults in Nepal. Approximatley half of the sample were former child soldiers in the Nepal People's War and the other half were demographically similiar civilian non-combatants. In addition to basic demographic characteristics (age, sex, ethnic minority status, social caste status, education level), participants were also assessed on syptoms of post-traumatic stress (PTS, assessed by a culturally adapted version of The Child PTSD Symptom Scale; Kohrt BA, et al. (2011) Validation of cross-cultural child mental health and psychosocial research instruments: adapting the Depression Self-Rating Scale and Child PTSD Symptom Scale in Nepal. BMC Psychiatry 11(1):e127, with higher values indicating greater PTSD symptoms) and psychological resilience (assessed by a culturally adapted version of the Resilience Scale; Wagnild GM & Young HM (1993) Development and psychometric evaluation of the Resilience Scale. Journal of Nursing Measurement, with higher values indicating greater resilience). Dichotomous variables were coded 0=no/absent and 1=yes/present. Valid gene expression data are available for 254 samples.
2016-07-27 | E-GEOD-77164 | biostudies-arrayexpress
Project description:Modification of microRNA sequences by the 3' addition of nucleotides to generate so-called M-bM-^@M-^\isomiRsM-bM-^@M-^] adds to the complexity of miRNA function, with recent reports showing that 3' modifications can influence miRNA stability and efficiency of target repression. Here we show that the 3' modification of miRNAs is a physiological and common post-transcriptional event that shows selectivity for specific miRNAs and is observed across species ranging from C. elegans to human. The modifications result predominantly from adenylation and uridylation, and are seen across tissue types, disease states, and developmental stages. To quantitatively profile 3' nucleotide additions, we developed and validated a novel assay based on NanoString Technologies' nCounter platform. For certain miRNAs, the frequency of modification was altered by processes such as cell differentiation, indicating that 3' modification is a biologically regulated process. To investigate the mechanism of 3' nucleotide additions, we used RNA interference to screen a panel of eight candidate miRNA nucleotidyl transferases for 3' miRNA modification activity in human cells. Multiple enzymes, including PAPD1, PAPD4, PAPD5, ZCCHC6, ZCCHC11, and TUT1, were found to govern 3' nucleotide addition to miRNAs in a miRNA-specific manner. Three of these enzymesM-bM-^@M-^SPAPD1, ZCCHC6 and TUT1M-bM-^@M-^Shave not previously been known to modify miRNAs. Collectively, our results indicate that 3' modification observed in next generation small RNA sequencing data is a biologically relevant process, and identify enzymatic mechanisms that may lead to new approaches for modulating miRNA activity in vivo. We validated the specificity of the platform by assaying three pools of synthetic RNA oligonucleotides representing canonical, variant 1, and variant 2 versions of 5 miRNAs (miR-15a, miR-15b, miR-125a-5p, miR-143 and miR-221).Each bridge pool (i.e., specific to canonical, variant 1 or variant 2) was used to assay the three mixtures of synthetic miRNA oligonucleotides. In order to assess accuracy, we also assayed mixtures of 5 synthetic miRNAs containing 60% canonical miRNA, 30% variant 1, and 10% variant 2. Triplicate technical replicates of each sample were performed.
2011-06-15 | E-GEOD-26916 | biostudies-arrayexpress