scholarly journals Genetic Variant rs755622 Regulates Expression of the Multiple Sclerosis Severity Modifier D-Dopachrome Tautomerase in a Sex-Specific Way

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Zhijie Han ◽  
Jiaojiao Qu ◽  
Jiehong Zhao ◽  
Xiao Zou
Keyword(s):  
Multiple Sclerosis ◽  
Macrophage Migration Inhibitory Factor ◽  
Large Scale ◽  
Genetic Variant ◽  
Differential Expression Analysis ◽  
Promoter Sequence ◽  
Minor Allele ◽  
Rna Seq ◽  
Dopachrome Tautomerase ◽  
Allele Variant

Multiple sclerosis (MS) is a sex-specific autoimmune disease involving central nervous system. Previous studies determined that macrophage migration inhibitory factor (MIF) and its homologue D-dopachrome tautomerase (DDT) sex-specifically affect MS progression. Moreover, other studies reported that rs755622 polymorphism in promoter region of MIF gene is associated with risk of MS and affects the promoter activity to regulate MIF expression in a sex-specific way. Given that MIF and DDT share a part of promoter sequence, we surmise that rs755622 can also regulate DDT expression in a sex-specific way. However, this has not yet been studied. Here, we used five large-scale expression quantitative trait loci (eQTLs) and two RNA-seq datasets from brain and blood to assess the potential influence of rs755622 variant on expression of DDT in different genders by the linear regression and differential expression analysis. The results show that the minor allele frequency of rs755622 and expression of DDT are significantly increased in males for MS subjects and this minor allele variant can significantly upregulate DDT expression for males but not females, which suggests that the regulation of DDT expression level by rs755622 can affect MS progression in males. These findings further support and expand conclusions of previous studies and may help to better understand the mechanisms of MS.

scholarly journals Leveraging high-powered RNA-Seq datasets to improve inference of regulatory activity in single-cell RNA-Seq data

2019 ◽  
Author(s):  
Ning Wang ◽  
Andrew E. Teschendorff
Keyword(s):  
Transcription Factors ◽  
Single Cell ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Large Scale ◽  
Single Cells ◽  
Differential Expression Analysis ◽  
Dropout Rate ◽  
Rna Seq ◽  
Regulatory Activity

AbstractInferring the activity of transcription factors in single cells is a key task to improve our understanding of development and complex genetic diseases. This task is, however, challenging due to the relatively large dropout rate and noisy nature of single-cell RNA-Seq data. Here we present a novel statistical inference framework called SCIRA (Single Cell Inference of Regulatory Activity), which leverages the power of large-scale bulk RNA-Seq datasets to infer high-quality tissue-specific regulatory networks, from which regulatory activity estimates in single cells can be subsequently obtained. We show that SCIRA can correctly infer regulatory activity of transcription factors affected by high technical dropouts. In particular, SCIRA can improve sensitivity by as much as 70% compared to differential expression analysis and current state-of-the-art methods. Importantly, SCIRA can reveal novel regulators of cell-fate in tissue-development, even for cell-types that only make up 5% of the tissue, and can identify key novel tumor suppressor genes in cancer at single cell resolution. In summary, SCIRA will be an invaluable tool for single-cell studies aiming to accurately map activity patterns of key transcription factors during development, and how these are altered in disease.

scholarly journals Genes highly overexpressed in salt-stressed Young oil palm (Elaeis guineensis) plants

2021 ◽  
Vol 25 (12) ◽  
pp. 813-818
Author(s):  
Thalita M. M. Ferreira ◽  
André P. Leão ◽  
Carlos A. F. de Sousa ◽  
Manoel T. Souza Júnior
Keyword(s):  
Salt Stress ◽  
Oil Palm ◽  
Large Scale ◽  
Elaeis Guineensis ◽  
Differential Expression Analysis ◽  
Gene Promoter ◽  
Rna Seq ◽  
Over Expression ◽  
Sequencing Platforms

ABSTRACT RNA-seq is a technique based on the large-scale sequencing of transcript-derived cDNAs using next-generation sequencing platforms mostly used today to characterize an organism’s transcriptome. The analysis of RNA-seq data allows for identifying genes differentially expressed in a given condition, such as salt stress. This study aimed to search and characterize genes from the African oil palm (Elaeis guineensis Jacq.) highly up-regulated during salt stress, with a long-term goal of gene promoter prospection and validation. The apical leaves from the control (electrical conductivity of ~2 dS m-1) and salt-stressed (~40 dS m-1) young oil palm plants, collected at 5 and 12 days after the beginning of the stress, were subjected to extraction of total RNA, with three plants (replicates) per treatment. The complete genome ofE. guineensis, available at the National Center for Biotechnology Information, was used as the reference genome - BioProject PRJNA192219. The differential expression analysis led to the selection for further characterization of seven genes, which had increased expressions of 37-84 times under salt stress. The strategy used in this study enabled the selection of seven salt-responsive genes highly up-regulated during salt stress, and some of them coded for proteins already reported as responsible for salinity tolerance in other plant species through over-expression or knockout.

RNA-Seq profiling of leukocytes reveals a sex-dependent global circular RNA upregulation in multiple sclerosis and 6 candidate biomarkers

2020 ◽  
Vol 29 (20) ◽  
pp. 3361-3372
Author(s):  
Leire Iparraguirre ◽  
Ainhoa Alberro ◽  
Lucía Sepúlveda ◽  
Iñaki Osorio-Querejeta ◽  
Laura Moles ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Differential Expression Analysis ◽  
Area Under The Curve ◽  
Circular Rna ◽  
Circular Rnas ◽  
Rna Seq ◽  
Paired Samples ◽  
The Central Nervous System ◽  
Chronic Autoimmune Disease ◽  
Diagnosis Classification

Abstract Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, with higher prevalence in women, that leads to neurological disability. The disease course and clinical phenotype are highly variable, and therefore, biomarkers for the diagnosis, classification, monitoring of the disease and treatment assessment are needed. Studies have shown a dysregulation in the coding and non-coding RNAs and proposed some as biomarkers. However, still none of them have reached the clinical practice. Recently, circular RNAs (circRNAs) have emerged as new players in the transcriptome that hold a great potential as biomarkers in several diseases. Leukocytes from 30 MS patients and 20 healthy controls (HCs) were RNA-sequenced to study the linear and circular transcriptome. Differential expression analysis was performed by DESeq, and circRNA candidates were studied in a second cohort (70 MS and 46 HC) by RT-qPCR and in paired samples drawn during the relapse and remission phases (20 patients). Among the differentially expressed circRNAs, 96.1% are upregulated in patients compared with controls, but similar circRNA profiles are found between MS types. The same upregulation trend was observed in females but not in males or in the linear transcriptome. The upregulation of 6 circRNAs was validated, and a change in their expression was found between relapse and remission. The 6 circRNAs showed a good performance to discriminate patients from HC with a combined area under the curve of 0.852. There is global, specific and sex-dependent increase of circRNA expression in MS, and 6 circRNAs are proposed as potential biomarkers.

scholarly journals Upregulated Expression of Macrophage Migration Inhibitory Factor, Its Analogue D-Dopachrome Tautomerase, and the CD44 Receptor in Peripheral CD4 T Cells from Clinically Isolated Syndrome Patients with Rapid Conversion to Clinical Defined Multiple Sclerosis

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 667 ◽  
Author(s):  
Cavalli ◽  
Mazzon ◽  
Basile ◽  
Mangano ◽  
Di Marco ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Migration Inhibitory Factor ◽  
Cd4 T Cells ◽  
Macrophage Migration Inhibitory Factor ◽  
Clinically Isolated Syndrome ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Healthy Controls ◽  
Dopachrome Tautomerase

Background and objectives: Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT) are two pleiotropic and primarily, but not exclusively, proinflammatory cytokines belonging to the MIF family of cytokines that have recently been shown to be implicated in the pathogenesis of progressive forms of human progressive Multiple Sclerosis (MS) and the experimental model counterpart in rodents. Materials and Methods: We have presently evaluated a transcriptomic analysis of the expression of MIF, DDT, their receptors CD74 and CD44, and MIF co-receptors CXCR2, CXCR4, and CXCR7 in peripheral blood of patients with Clinically Isolated Syndrome (CIS), with rapid progression to clinical defined MS. Results: Our analysis reveals that MIF, DDT, and CD44 are overexpressed in CD4+ T cells from patients with CIS, as compared to healthy controls. Accordingly, a significant overlap was observed between the genes overexpressed in CD4+ T cells from patients with CIS and the genes belonging to the MIF regulatory network. This upregulated expression appeared to be unique for CD4+T cells, as other immune cells including CD8+ T cells, B cells, and monocytes from these patients exhibited expression levels of these molecules that were superimposable to those observed in healthy controls. Conclusions: Overall, our data suggest that the overexpression MIF cytokine family signature may occur in CD4+ T cells from patients with CIS, and that this phenomenon may be implicated in the pathogenesis of the disease, offering the possibility to represent both a diagnostic marker and a therapeutic target.

scholarly journals recount: A large-scale resource of analysis-ready RNA-seq expression data

2016 ◽  
Author(s):  
Leonardo Collado-Torres ◽  
Abhinav Nellore ◽  
Kai Kammers ◽  
Shannon E. Ellis ◽  
Margaret A. Taub ◽  
...  
Keyword(s):  
Large Scale ◽  
Meta Analysis ◽  
Differential Expression Analysis ◽  
Expression Data ◽  
Rna Seq ◽  
Base Level ◽  
Genomic Annotation ◽  
Public Data ◽  
Using Data ◽  
Splice Junctions

Abstractrecount is a resource of processed and summarized expression data spanning nearly 60,000 human RNA-seq samples from the Sequence Read Archive (SRA). The associated recount Bio-conductor package provides a convenient API for querying, downloading, and analyzing the data. Each processed study consists of meta/phenotype data, the expression levels of genes and their underlying exons and splice junctions, and corresponding genomic annotation. We also provide data summarization types for quantifying novel transcribed sequence including base-resolution coverage and potentially unannotated splice junctions. We present workflows illustrating how to use recount to perform differential expression analysis including meta-analysis, annotation-free base-level analysis, and replication of smaller studies using data from larger studies. recount provides a valuable and user-friendly resource of processed RNA-seq datasets to draw additional biological insights from existing public data. The resource is available at https://jhubiostatistics.shinyapps.io/recount/.

Fundamental study on clarification of brain molecular pathology of Nasu-Hakola disease

Impact ◽  
2019 ◽  
Vol 2019 (8) ◽  
pp. 24-26
Author(s):  
Jun-ichi Satoh
Keyword(s):  
Multiple Sclerosis ◽  
Human Brain ◽  
Clinical Research ◽  
Neurodegenerative Diseases ◽  
Molecular Pathology ◽  
Large Scale ◽  
Molecular Pathogenesis ◽  
Novel Therapies ◽  
Brain Pathology ◽  
Fundamental Study

Brain pathology expert Dr Jun-ichi Satoh, from the Department of Bioinformatics and Molecular Neuropathology of Meiji Pharmaceutical University in Tokyo, is drawing on his expertise on neurology and neuroimmunology to delve into some of the more complex diseases impacting the human brain. His knowledge and expertise have allowed him to direct his research interests to study neurodegenerative diseases, such as Alzheimer's disease (AD), and neuroinflammatory diseases, such as multiple sclerosis (MS), and the analysis of their molecular pathogenesis by using a bioinformatics approach. His current focus is on Nasu-Hakola disease (NHD), a disease whose rarity has posed significant barriers towards performing large-scale clinical research in order to understand what exactly causes this disease and develop effective novel therapies.

scholarly journals Transcriptional and morphological profiling of parvalbumin interneuron subpopulations in the mouse hippocampus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lin Que ◽  
David Lukacsovich ◽  
Wenshu Luo ◽  
Csaba Földy
Keyword(s):  
Large Scale ◽  
Cell Types ◽  
Rna Seq ◽  
Neuronal Identity ◽  
Parvalbumin Interneurons ◽  
Different Types ◽  
Parvalbumin Interneuron ◽  
Cam Profile ◽  
Developmental Domains

AbstractThe diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.

scholarly journals Best practices on the differential expression analysis of multi-species RNA-seq

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Matthew Chung ◽  
Vincent M. Bruno ◽  
David A. Rasko ◽  
Christina A. Cuomo ◽  
José F. Muñoz ◽  
...  
Keyword(s):  
Best Practices ◽  
Differential Expression ◽  
Expression Analysis ◽  
Differential Expression Analysis ◽  
Single Species ◽  
Rna Seq ◽  
Species Analysis ◽  
Differential Gene ◽  
Multiple Species ◽  
Downstream Analysis

AbstractAdvances in transcriptome sequencing allow for simultaneous interrogation of differentially expressed genes from multiple species originating from a single RNA sample, termed dual or multi-species transcriptomics. Compared to single-species differential expression analysis, the design of multi-species differential expression experiments must account for the relative abundances of each organism of interest within the sample, often requiring enrichment methods and yielding differences in total read counts across samples. The analysis of multi-species transcriptomics datasets requires modifications to the alignment, quantification, and downstream analysis steps compared to the single-species analysis pipelines. We describe best practices for multi-species transcriptomics and differential gene expression.

scholarly journals Gene Expression Profile and Co-Expression Network of Pearl Gentian Grouper under Cold Stress by Integrating Illumina and PacBio Sequences

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1745
Author(s):  
Ben-Ben Miao ◽  
Su-Fang Niu ◽  
Ren-Xie Wu ◽  
Zhen-Bang Liang ◽  
Bao-Gui Tang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cold Stress ◽  
Differential Expression Analysis ◽  
Endocrine System ◽  
Control Group ◽  
Regulation Mechanism ◽  
Rna Seq ◽  
Cold Tolerant ◽  
Stress Signals ◽  
Membrane Changes

Pearl gentian grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) is a fish of high commercial value in the aquaculture industry in Asia. However, this hybrid fish is not cold-tolerant, and its molecular regulation mechanism underlying cold stress remains largely elusive. This study thus investigated the liver transcriptomic responses of pearl gentian grouper by comparing the gene expression of cold stress groups (20, 15, 12, and 12 °C for 6 h) with that of control group (25 °C) using PacBio SMRT-Seq and Illumina RNA-Seq technologies. In SMRT-Seq analysis, a total of 11,033 full-length transcripts were generated and used as reference sequences for further RNA-Seq analysis. In RNA-Seq analysis, 3271 differentially expressed genes (DEGs), two low-temperature specific modules (tan and blue modules), and two significantly expressed gene sets (profiles 0 and 19) were screened by differential expression analysis, weighted gene co-expression networks analysis (WGCNA), and short time-series expression miner (STEM), respectively. The intersection of the above analyses further revealed some key genes, such as PCK, ALDOB, FBP, G6pC, CPT1A, PPARα, SOCS3, PPP1CC, CYP2J, HMGCR, CDKN1B, and GADD45Bc. These genes were significantly enriched in carbohydrate metabolism, lipid metabolism, signal transduction, and endocrine system pathways. All these pathways were linked to biological functions relevant to cold adaptation, such as energy metabolism, stress-induced cell membrane changes, and transduction of stress signals. Taken together, our study explores an overall and complex regulation network of the functional genes in the liver of pearl gentian grouper, which could benefit the species in preventing damage caused by cold stress.

scholarly journals Differential Expression Analysis of Phytohormone-Related Genes of Korean Wheat (Triticum aestivum) in Response to Preharvest Sprouting and Abscisic Acid (ABA)

2021 ◽  
Vol 11 (8) ◽  
pp. 3562
Author(s):  
Yong Jin Lee ◽  
Sang Yong Park ◽  
Dae Yeon Kim ◽  
Jae Yoon Kim
Keyword(s):  
Abscisic Acid ◽  
Differential Expression Analysis ◽  
Preharvest Sprouting ◽  
Global Changes ◽  
Rna Seq ◽  
Hormone Metabolism ◽  
Global Issue ◽  
End Use ◽  
Transcriptomic Changes

Preharvest sprouting (PHS) is a key global issue in production and end-use quality of cereals, particularly in regions where the rainfall season overlaps the harvest. To investigate transcriptomic changes in genes affected by PHS-induction and ABA-treatment, RNA-seq analysis was performed in two wheat cultivars that differ in PHS tolerance. A total of 123 unigenes related to hormone metabolism and signaling for abscisic acid (ABA), gibberellic acid (GA), indole-3-acetic acid (IAA), and cytokinin were identified and 1862 of differentially expressed genes were identified and divided into 8 groups by transcriptomic analysis. DEG analysis showed the majority of genes were categorized in sugar related processes, which interact with ABA signaling in PHS tolerant cultivar under PHS-induction. Thus, genes related to ABA are key regulators of dormancy and germination. Our results give insight into global changes in expression of plant hormone related genes in response to PHS.

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