scholarly journals Agonal Factors Distort Gene-Expression Patterns in Human Postmortem Brains

2021 ◽  
Vol 15 ◽  
Author(s):  
Jiacheng Dai ◽  
Yu Chen ◽  
Rujia Dai ◽  
Yi Jiang ◽  
Jianghua Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Brain Cell ◽  
Terminal State ◽  
Specific Gene ◽  
Brain Gene Expression ◽  
Postmortem Brains ◽  
Cell Type Specific ◽  
Study Designs

Agonal factors, the conditions that occur just prior to death, can impact the molecular quality of postmortem brains, influencing gene expression results. Our study used gene expression data of 262 samples from ROSMAP with the detailed terminal state recorded for each donor, such as fever, infection, and unconsciousness. Fever and infection were the primary contributors to brain gene expression changes, brain cell-type-specific gene expression, and cell proportion changes. Furthermore, we also found that previous studies of gene expression in postmortem brains were confounded by agonal factors. Therefore, correction for agonal factors is important in the step of data preprocessing. Our analyses revealed fever and infection contributing to gene expression changes in postmortem brains and emphasized the necessity of study designs that document and account for agonal factors.

scholarly journals Agonal factors distort gene-expression patterns in human postmortem brains

2020 ◽  
Author(s):  
Jiacheng Dai ◽  
Yu Chen ◽  
Chao Chen ◽  
Chunyu Liu
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Postmortem Brain ◽  
Gene Expression Patterns ◽  
Specific Gene ◽  
Surrogate Variable Analysis ◽  
Network Analyses ◽  
Postmortem Brain Tissue ◽  
Postmortem Brains ◽  
Study Designs

AbstractAgonal factors, the conditions that occur just prior to death, can impact the molecular quality of postmortem brains, influencing gene expression results. Nevertheless, study designs using postmortem brain tissue rarely, if ever, account for these factors, and previous studies had not documented nor adjusted for agonal factors. Our study used gene expression data of 262 samples from ROSMAP with the following terminal states recorded for each donor: surgery, fever, infection, unconsciousness, difficulty breathing, and mechanical ventilation. Performed differential gene expression and weighted gene co-expression network analyses (WGCNA), fever and infection were the primary contributors to brain gene expression changes. Fever and infection also contributed to brain cell-type specific gene expression and cell proportion changes. Furthermore, the gene expression patterns implicated in fever and infection were unique to other agonal factors. We also found that previous studies of gene expression in postmortem brains were confounded by variables of hypoxia or oxygen level pathways. Therefore, correction for agonal factors through probabilistic estimation of expression residuals (PEER) or surrogate variable analysis (SVA) is recommended to control for unknown agonal factors. Our analyses revealed fever and infection contributing to gene expression changes in postmortem brains and emphasized the necessity of study designs that document and account for agonal factors.

scholarly journals Microgenomic analysis reveals cell type-specific gene expression patterns between ray and fusiform initials within the cambial meristem ofPopulus

2008 ◽  
Vol 180 (1) ◽  
pp. 45-56 ◽  
Author(s):  
Nadia Goué ◽  
Marie-Claude Lesage-Descauses ◽  
Ewa J. Mellerowicz ◽  
Elisabeth Magel ◽  
Philippe Label ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Fusiform Initials ◽  
Cell Type Specific

scholarly journals Varying intolerance of gene pathways to mutational classes explain genetic convergence across neuropsychiatric disorders

2016 ◽  
Author(s):  
Shahar Shohat ◽  
Eyal Ben-David ◽  
Sagiv Shifman
Keyword(s):  
Gene Expression ◽  
Genome Wide Association Study ◽  
De Novo ◽  
Expression Patterns ◽  
Neuropsychiatric Disorders ◽  
Autism Spectrum ◽  
Specific Gene ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Brain Gene Expression

AbstractGenetic susceptibility to Intellectual disability (ID), autism spectrum disorder (ASD) and schizophrenia (SCZ) often arises from mutations in the same genes, suggesting that they share common mechanisms. We studied genes with de novo mutations in the three disorders and genes implicated by SCZ genome-wide association study (GWAS). Using biological annotations and brain gene expression, we show that mutation class explains enrichment patterns more than specific disorder. Genes with loss of function mutations and genes with missense mutations were enriched with different pathways, shared with genes intolerant to mutations. Specific gene expression patterns were found for each disorder. ID genes were preferentially expressed in fetal cortex, ASD genes also in fetal cerebellum and striatum, and genes associated with SCZ were most significantly enriched in adolescent cortex. Our study suggests that convergence across neuropsychiatric disorders stems from vulnerable pathways to genetic variations, but spatiotemporal activity of genes contributes to specific phenotypes.

scholarly journals CT-FOCS: a novel method for inferring cell type-specific enhancer-promoter maps

2019 ◽  
Author(s):  
Tom Aharon Hait ◽  
Ran Elkon ◽  
Ron Shamir
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Expression Patterns ◽  
Cell Types ◽  
Specific Gene ◽  
Cell Type ◽  
Chromatin Interactions ◽  
Cell Type Specific ◽  
Novel Method ◽  
Validation Scheme

AbstractSpatiotemporal gene expression patterns are governed to a large extent by enhancer elements, typically located distally from their target genes. Identification of enhancer-promoter (EP) links that are specific and functional in individual cell types is a key challenge in understanding gene regulation. We introduce CT-FOCS, a new statistical inference method that utilizes multiple replicates per cell type to infer cell type-specific EP links. Computationally predicted EP links are usually benchmarked against experimentally determined chromatin interactions measured by ChIA-PET and promoter-capture HiC techniques. We expand this validation scheme by using also loops that overlap in their anchor sites. In analyzing 1,366 samples from ENCODE, Roadmap epigenomics and FANTOM5, CT-FOCS inferred highly cell type-specific EP links more accurately than state-of-the-art methods. We illustrate how our inferred EP links drive cell type-specific gene expression and regulation.

Maternal oxytocin administration modulates gene expression in the brains of perinatal mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Frances F. Hsieh ◽  
Ilya Korsunsky ◽  
Andrew J. Shih ◽  
Matthew A. Moss ◽  
Prodyot K. Chatterjee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neurite Outgrowth ◽  
Quantitative Pcr ◽  
Expression Patterns ◽  
Specific Gene ◽  
Neonatal Brain ◽  
Real Time Quantitative Pcr ◽  
Brain Gene Expression ◽  
Gene Expression Analyses ◽  
Differential Gene

Abstract Objectives Oxytocin (OXT) is widely used to facilitate labor. However, little is known about the effects of perinatal OXT exposure on the developing brain. We investigated the effects of maternal OXT administration on gene expression in perinatal mouse brains. Methods Pregnant C57BL/6 mice were treated with saline or OXT at term (n=6–7/group). Dams and pups were euthanized on gestational day (GD) 18.5 after delivery by C-section. Another set of dams was treated with saline or OXT (n=6–7/group) and allowed to deliver naturally; pups were euthanized on postnatal day 9 (PND9). Perinatal/neonatal brain gene expression was determined using Illumina BeadChip Arrays and real time quantitative PCR. Differential gene expression analyses were performed. In addition, the effect of OXT on neurite outgrowth was assessed using PC12 cells. Results Distinct and sex-specific gene expression patterns were identified in offspring brains following maternal OXT administration at term. The microarray data showed that female GD18.5 brains exhibited more differential changes in gene expression compared to male GD18.5 brains. Specifically, Cnot4 and Frmd4a were significantly reduced by OXT exposure in male and female GD18.5 brains, whereas Mtap1b, Srsf11, and Syn2 were significantly reduced only in female GD18.5 brains. No significant microarray differences were observed in PND9 brains. By quantitative PCR, OXT exposure reduced Oxtr expression in female and male brains on GD18.5 and PND9, respectively. PC12 cell differentiation assays revealed that OXT induced neurite outgrowth. Conclusions Prenatal OXT exposure induces sex-specific differential regulation of several nervous system-related genes and pathways with important neural functions in perinatal brains.

scholarly journals Systemic and cell type-specific gene expression patterns in scleroderma skin

2003 ◽  
Vol 100 (21) ◽  
pp. 12319-12324 ◽  
Author(s):  
M. L. Whitfield ◽  
D. R. Finlay ◽  
J. I. Murray ◽  
O. G. Troyanskaya ◽  
J.-T. Chi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Cell Type Specific

scholarly journals Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning

2021 ◽  
Author(s):  
Elizabeth Ing-Simmons ◽  
Roshan Vaid ◽  
Xin Yang Bing ◽  
Michael Levine ◽  
Mattias Mannervik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Expression Patterns ◽  
Chromatin Organization ◽  
Specific Gene ◽  
Chromatin Conformation ◽  
Dorsoventral Patterning ◽  
Tissue Specific ◽  
Cell Type Specific ◽  
The Relationship

AbstractThe relationship between chromatin organization and gene regulation remains unclear. While disruption of chromatin domains and domain boundaries can lead to misexpression of developmental genes, acute depletion of regulators of genome organization has a relatively small effect on gene expression. It is therefore uncertain whether gene expression and chromatin state drive chromatin organization or whether changes in chromatin organization facilitate cell-type-specific activation of gene expression. Here, using the dorsoventral patterning of the Drosophila melanogaster embryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.

scholarly journals Brain Cell Type Specific Gene Expression and Co-expression Network Architectures

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Andrew T. McKenzie ◽  
Minghui Wang ◽  
Mads E. Hauberg ◽  
John F. Fullard ◽  
Alexey Kozlenkov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Cell ◽  
Specific Gene ◽  
Network Architectures ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Cell Type Specific
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