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Attention to time-of-day variability improves the reproducibility of gene expression patterns in multiple sclerosis

ABSTRACT: Attention to time-of-day variability improves the reproducibility of gene expression patterns in multiple sclerosis

PROVIDER: PRJNA631782 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11773136.fastq.gz	Fastqsanger.gz
	SRR11773137.fastq.gz	Fastqsanger.gz
	SRR11773138.fastq.gz	Fastqsanger.gz
	SRR11773139.fastq.gz	Fastqsanger.gz
	SRR11773140.fastq.gz	Fastqsanger.gz

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Attention to time-of-day variability improves the reproducibility of gene expression patterns in multiple sclerosis

Project description:Most biomarkers for the diagnosis and prognosis of multiple sclerosis (MS) are not yet clinically available due to low reproducibility. Here, we show that times of day affect gene expression profiles in MS patients. Thus sample collection has to be standardized based on the time-points biomarkers are expressed to increase reproducibility. In this study, we examined transcriptome profiles in whole blood of MS patients collected at two different time-points of the day, around 2 pm as the daytime and 9 pm as the nighttime. We observed the significantly changed gene expression profiles in the relapsing patients at nighttime compared to their daytime samples and the remitting patients at nighttime. Among all DEGs, we focused on differentially expressed genes (DEGs) related to immune responses because of association with clinical outcomes of MS. 68 immune responses-associated DEGs significantly changed their expression in the relapsing patients at nighttime but not in their daytime samples and remitting patients at nighttime. Therefore, this study shows that: 1) gene expresion patterns in relapsing patients are changed compared to remitting patients; 2) altered gene expression patterns in relpasing patients are detected at nighttim; 3) times of day to collect samples from MS patients should be standardized based on the gene expression patterns across a day.

2021-11-03 | GSE150337 | GEO

Attention to time-of-day variability improves the reproducibility of gene expression patterns in multiple sclerosis.

Project description:Low reproducibility in gene expression profiles has been observed in transcriptome studies, and this often limits applying findings to clinical practice. Here, we show time-of-day effects on gene expression and analytical schemes to increase the reproducibility in expression patterns. We recruited patients with relapsing-remitting multiple sclerosis (RRMS) and healthy subjects and collected blood from individuals twice a day, day (2 pm) and night (9 pm). RNA sequencing analyses found that gene expression in RRMS in relapse (Relapse) is significantly changed at night compared with either Relapse at day or RRMS in remission (Remission). Gene set overrepresentation analysis demonstrated that gene sets significantly changed in Relapse at night are enriched to immune responses related to MS pathology. In those gene sets, 68 genes are significantly changed expression in Relapse at night compared with Relapse at day and Remission. This supports that times of sample collections should be standardized to obtain reproducible gene expression patterns.

| S-EPMC8551071 | biostudies-literature

Stress regulation of sustained attention and the cholinergic attention system

Project description:Stress regulation of sustained attention and the cholinergic attention system

| PRJNA619064 | ENA

Stress regulation of sustained attention and the cholinergic attention system

Project description:Background: Stress exacerbates symptoms of schizophrenia and attention deficit hyperactivity disorder, which are characterized by impairments in sustained attention. Yet how stress regulates attention remains largely unexplored. Here we investigated whether a 6-day variable stressor (VS) altered sustained attention and the cholinergic attention system in male and female rats. Methods: Sustained attention was tested with the sustained attention task (SAT). Successful performance on SAT relies on the release of acetylcholine (ACh) into the cortex from cholinergic neurons in the nucleus basalis of Meynert (NBM). Thus, we evaluated whether VS altered the morphology of these neurons with a novel approach using Cre-dependent virus in genetically modified ChAT::Cre rats, a species used for this manipulation only. Next, electrochemical recordings measured cortical ACh following VS. Finally, we used RNAseq to identify VS-induced transcriptional changes in the NBM. Results: VS impaired attentional performance in SAT and increased the dendritic complexity of NBM cholinergic neurons in both sexes. NBM cholinergic neurons are mainly under inhibitory control, so this morphological change could increase inhibition on these neurons, reducing downstream ACh release to impair attention. Indeed, VS decreased ACh release in the prefrontal cortex of males. Quantification of global transcriptional changes revealed that, although VS induced many sex-specific changes in gene expression, it increased several signaling molecules in both sexes.

2020-05-01 | GSE147806 | GEO

Reproducibility of molecular phenotypes after long-term differentiation to Human iPSC-Derived Neurons: a multi-site omics study [bulk]

Project description:Reproducibility in molecular and cellular studies is fundamental to scientific discovery. To establish the reproducibility of a well-defined long term neuronal differentiation protocol, we repeated the cellular and molecular comparison of the same two iPSC lines across five distinct laboratories. Despite uncovering acceptable variability within individual laboratories, we detect poor cross-site reproducibility of the differential gene expression signature between these two lines. Factor analysis identifies the laboratory as the largest source of variation along with several variation-inflating confounds such as passaging effects and progenitor storage. Single cell transcriptomics shows substantial cellular heterogeneity underlying inter-laboratory variability and being responsible for biases in differential gene expression inference. Factor analysis-based normalization of the combined dataset can remove the nuisance technical effects, enabling the execution of robust hypothesis generating studies. Our study shows that multi-center collaborations can expose systematic biases and identify critical factors to be standardized when publishing novel protocols, contributing to increased cross-site reproducibility.

2018-08-20 | GSE118733 | GEO

Reproducibility of molecular phenotypes after long-term differentiation to Human iPSC-Derived Neurons: a multi-site omics study [single-cell]

2018-08-20 | GSE118734 | GEO

Epigenome-wide DNA methylation profiling in CD4+ and CD8+ T cells from patients with multiple sclerosis and healthy controls followed during (1st, 2nd and 3rd trimester) and after pregnancy

Project description:Patient with multiple sclerosis improves during pregnancy while temporarily worsening post-partum. The reasons behind the disease modulation during pregnancy remain unknown. In this study, we have investigated the effect of pregnancy on circulating CD4+ and CD8+ T cells from patients with multiple sclerosis and healthy controls to gain a deeper understanding why patients with multiple sclerosis improves during pregnancy. We assessed transcriptomics in CD4+ and CD8+ T cells obtained during (1st, 2nd and 3rd trimester) and after pregnancy (6 weeks post-partum), using the RNA-seq.

2023-08-02 | E-MTAB-12260 | biostudies-arrayexpress

Epigenome-wide DNA methylation profiling in CD4+ and CD8+ T cells from patients with multiple sclerosis and healthy controls followed during (1st, 2nd and 3rd trimester) and after pregnancy.

Project description:Patient with multiple sclerosis improves during pregnancy while temporarily worsening post-partum. The reasons behind the disease modulation during pregnancy remain unknown. In this study, we have investigated the effect of pregnancy on circulating CD4+ and CD8+ T cells from patients with multiple sclerosis and healthy controls to gain a deeper understanding why patients with multiple sclerosis improves during pregnancy. We assessed epigenome-wide DNA methylation in CD4+ and CD8+ T cells obtained during (1st, 2nd and 3rd trimester) and after pregnancy (6 weeks post-partum), using the Infinium MethylationEPIC 850K array.

2023-09-23 | E-MTAB-12250 | biostudies-arrayexpress

1H-NMR Reproducibility

Project description:The purpose of this study is to prepare and analyze a set of samples that will test the experimental variability and reproducibility of NMR based metabolomics.

| ST000018 | MetabolomicsWorkbench

Wild-type Heterogeneity Contributes to Clonal Variability in Genome-Edited Cells

Project description:Phenotypic variability among different knockout clones of the same gene is a common problem confounding the establishment of robust genotype-phenotype correlations. Optimized genome editing protocols to enhance reproducibility include measures to reduce off-target effects. However, even if current state-of-the-art protocols are applied phenotypic variability is frequently observed. Here we identify heterogeneity of wild-type cells as an important and often neglected confounding factor in genome-editing experiments. We demonstrate that isolation of individual wild-type clones from an apparently homogenous stable cell line uncovers significant phenotypic differences between clones. Strikingly, we observe hundreds of differentially regulated transcripts when comparing two populations of wild-type cells. Heterogeneity of wild-type cells thus contributes to variability in genome-edited cells when these are generated through isolation of clones. We show that the generation of monoclonal isogenic wild-type cells prior to genomic manipulation reduces phenotypic variability.

2022-02-18 | GSE196762 | GEO

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