Small RNA sequencing revealed dysregulated piRNAs in Alzheimer's disease and their probable role in pathogenesis

2017 ◽  
Vol 13 (3) ◽  
pp. 565-576 ◽  
Author(s):  
Jyoti Roy ◽  
Arijita Sarkar ◽  
Sibun Parida ◽  
Zhumur Ghosh ◽  
Bibekanand Mallick
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Rna Sequencing ◽  
Small Rna ◽  
Small Rna Sequencing ◽  
Healthy Human ◽  
Probable Role ◽  
First Time

For the first time, this study reports specific piRNA signatures in a healthy human brain and an AD-diagnosed brain and decrypted the regulatory roles of dysregulated piRNAs in the pathogenesis of AD.

2181The prothrombotic transcriptome of reticulated platelets

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Bongiovanni ◽  
G Santamaria ◽  
M Klug ◽  
D Santovito ◽  
A Felicetta ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Platelet Activation ◽  
Small Rna ◽  
Peripheral Blood ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Gene Set Enrichment Analysis ◽  
Small Rna Sequencing ◽  
Reticulated Platelets ◽  
First Time

Abstract Introduction Reticulated platelets (RPs) are young, hyper-reactive platelets that are larger and contain significantly more RNA compared to older mature platelets. High levels of RPs in peripheral blood are predictors of an insufficient response to dual antiplatelet therapy in cardiovascular patients and of adverse cardiovascular events also in non-cardiac patients. However, the mechanisms underlying these correlations remains widely unknown and the biology of RPs has not been investigated yet. Purpose We aimed to compare for the first time the transcriptomic profiles of RPs and mature platelets (MPs). Methods RPs and MPs from peripheral blood of healthy donors were identified and isolated using FACS/Sorting based on their RNA-content. Immediately after sorting, RNA was extracted and quality, concentration and integrity was assessed with the Tapestation 4200 platform (Agilent). Total- and small-RNA libraries were prepared, multiplexed and sequenced on a NextSeq 500 Illumina platform Results Total-RNA-sequencing revealed 1744 differentially expressed genes (670 downregulated 1074 upregulated) in RPs compared to MPs (Figure 1A, B). In particular, transcripts for the collagen receptor GP6, thromboxane receptor A2 (TBXA2R), thrombin receptor PAR4 (F2RL3) and ATP receptor P2RX1 were significantly enriched in RPs, whereas several RNA regulators as the ribonuclease PARN, the RISC-component TNRC6A and the splicing factor LUC7L3 were downregulated in RPs. Gene ontology analysis revealed an enrichment of relevant biological categories in RPs including platelet activation and blood coagulation (Figure 1C). Gene Set Enrichment Analysis showed an enrichment of several activation pathways like thrombin, thromboxane and GPIIb/IIIa signaling in RPs. Small-RNA-sequencing reported 9 miRNAs significantly downregulated in RPs with targets involved in platelet reactivity. Figure 1 Conclusions This study represents the first comparative transcriptome analysis of RPs and MPs and reports for the first time a differential enrichment of transcripts involved in platelet activation. The clear upregulation of prothrombotic signaling in RPs could explain, at least in part, their hyper-activity and their correlation with cardiovascular events in different pathological settings (trancripts enriched in RPs: Figure 1D). Acknowledgement/Funding German Society of Cardiology (DGK Nr.102018) ESC First conctact initiative grant 2018

scholarly journals MicroRNA-Seq Data Analysis Pipeline to Identify Blood Biomarkers for Alzheimer's Disease from Public Data

2015 ◽  
Vol 10 ◽  
pp. BMI.S25132 ◽  
Author(s):  
Jun-ichi Satoh ◽  
Yoshihiro Kino ◽  
Shumpei Niida
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Data Analysis ◽  
Small Rna ◽  
Small Rna Sequencing ◽  
Rna Seq ◽  
Analysis Pipeline ◽  
Web Based ◽  
Public Data ◽  
Data Analysis Pipeline

Background Alzheimer's disease (AD) is the most common cause of dementia with no curative therapy currently available. Establishment of sensitive and non-invasive biomarkers that promote an early diagnosis of AD is crucial for the effective administration of disease-modifying drugs. MicroRNAs (miRNAs) mediate posttranscriptional repression of numerous target genes. Aberrant regulation of miRNA expression is implicated in AD pathogenesis, and circulating miRNAs serve as potential biomarkers for AD. However, data analysis of numerous AD-specific miRNAs derived from small RNA-sequencing (RNA-Seq) is most often laborious. Methods To identify circulating miRNA biomarkers for AD, we reanalyzed a publicly available small RNA-Seq dataset, composed of blood samples derived from 48 AD patients and 22 normal control (NC) subjects, by a simple web-based miRNA data analysis pipeline that combines omiRas and DIANA miRPath. Results By using omiRas, we identified 27 miRNAs expressed differentially between both groups, including upregulation in AD of miR-26b-3p, miR-28–3p, miR-30c-5p, miR-30d-5p, miR-148b-5p, miR-151a-3p, miR-186–5p, miR-425–5p, miR-550a-5p, miR-1468, miR-4781–3p, miR-5001–3p, and miR-6513–3p and downregulation in AD of let-7a-5p, let-7e-5p, let-7f-5p, let-7g-5p, miR-15a-5p, miR-17–3p, miR-29b-3p, miR-98–5p, miR-144–5p, miR-148a-3p, miR-502–3p, miR-660–5p, miR-1294, and miR-3200–3p. DIANA miRPath indicated that miRNA-regulated pathways potentially down– regulated in AD are linked with neuronal synaptic functions, while those upregulated in AD are implicated in cell survival and cellular communication. Conclusions The simple web-based miRNA data analysis pipeline helps us to effortlessly identify candidates for miRNA biomarkers and pathways of AD from the complex small RNA–Seq data.

scholarly journals Relationships of Alzheimer’s disease and apolipoprotein E genotypes with small RNA and protein cargo of brain tissue extracellular vesicles

2020 ◽  
Author(s):  
Yiyao Huang ◽  
Tom A. P. Driedonks ◽  
Lesley Cheng ◽  
Andrey Turchinovich ◽  
Harinda Rajapaksha ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Vesicles ◽  
Small Rna ◽  
Apoe Genotype ◽  
Tau Proteins ◽  
Small Rna Sequencing ◽  
Health Crisis ◽  
Metabolic Functions ◽  
Apolipoprotein E Genotypes

ABSTRACTAlzheimer’s disease (AD) is a public health crisis that grows as populations age. Hallmarks of this neurodegenerative disease include aggregation of beta-amyloid peptides and hyperphosphorylated tau proteins in the brain. Variants of the APOE gene are the greatest known risk factors for sporadic AD. As emerging players in AD pathophysiology, extracellular vesicles (EVs) contain proteins, lipids, and RNAs and are involved in disposal of cellular toxins and intercellular communication. AD-related changes in the molecular composition of EVs may contribute to pathophysiology and lend insights into disease mechanisms. We recently adapted a method for separation of brain-derived EVs (bdEVs) from post-mortem tissues. Using this method, we isolated bdEVs from AD patients with different APOE genotypes (n=23) and controls (n=7). bdEVs were counted, sized, and subjected to parallel small RNA sequencing and proteomic analysis. Numerous bdEV-associated RNAs and proteins correlated with AD pathology and APOE genotype. Some of the identified entities have been implicated previously in important AD-related pathways, including amyloid processing, neurodegeneration, and metabolic functions. These findings provide further evidence that bdEVs and their molecular cargo modulate development and progression of AD.

scholarly journals Functional segmentation of the hippocampus in the healthy human brain and in Alzheimer's disease

NeuroImage ◽  
2013 ◽  
Vol 66 ◽  
pp. 28-35 ◽  
Author(s):  
Mojtaba Zarei ◽  
Christian F. Beckmann ◽  
Maja A.A. Binnewijzend ◽  
Menno M. Schoonheim ◽  
Mohammad Ali Oghabian ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Healthy Human

scholarly journals Novel microRNA discovery using small RNA sequencing in post-mortem human brain

BMC Genomics ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Christian Wake ◽  
Adam Labadorf ◽  
Alexandra Dumitriu ◽  
Andrew G. Hoss ◽  
Joli Bregu ◽  
...  
Keyword(s):  
Human Brain ◽  
Rna Sequencing ◽  
Small Rna ◽  
Small Rna Sequencing ◽  
Post Mortem

scholarly journals 40 Hz Light Flicker Alters Human Brain Electroencephalography Microstates and Complexity Implicated in Brain Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Yiqi Zhang ◽  
Zhenyu Zhang ◽  
Lei Luo ◽  
Huaiyu Tong ◽  
Fei Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Future Development ◽  
Negative Control ◽  
Brain Diseases ◽  
Control Treatment ◽  
Healthy Human ◽  
Light Flicker ◽  
40 Hz

Previous studies showed that entrainment of light flicker at low gamma frequencies provided neuroprotection in mouse models of Alzheimer’s disease (AD) and stroke. The current study was set to explore the feasibility of using 40 Hz light flicker for human brain stimulation for future development as a tool for brain disease treatment. The effect of 40 Hz low gamma frequency light on a cohort of healthy human brains was examined using 64 channel electroencephalography (EEG), followed by microstate analyses. A random frequency light flicker was used as a negative control treatment. Light flicker at 40 Hz significantly increased the corresponding band power in the O1, Oz, and O3 electrodes covering the occipital areas of both sides of the brain, indicating potent entrainment with 40 Hz light flicker in the visual cortex area. Importantly, the 40 Hz light flicker significantly altered microstate coverage, transition duration, and the Lempel-Ziv complexity (LZC) compared to the rest state. Microstate metrics are known to change in the brains of Alzheimer’s disease, schizophrenia, and stroke patients. The current study laid the foundation for the future development of 40 Hz light flicker as therapeutics for brain diseases.

scholarly journals COMPASS: a COMprehensive Platform for smAll RNA-Seq data analySis

2019 ◽  
Author(s):  
Jiang Li ◽  
Alvin T. Kho ◽  
Robert P. Chase ◽  
Lorena Pantano-Rubino ◽  
Leanna Farnam ◽  
...  
Keyword(s):  
Data Analysis ◽  
Rna Sequencing ◽  
Small Rna ◽  
Small Rnas ◽  
Small Rna Sequencing ◽  
Sequencing Data ◽  
Healthy Human ◽  
Data Set ◽  
Sequence Processing ◽  
Rna Analysis

Abstract Background Circulating RNAs are potential disease biomarkers and their function is being actively investigated. Next generation sequencing (NGS) is a common means to interrogate the small RNA'ome or the full spectrum of small RNAs (<200 nucleotide length) of a biological system. A pivotal problem in NGS based small RNA analysis is identifying and quantifying the small RNA'ome constituent components. Most existing NGS data analysis tools focus on the microRNA component and a few other small RNA types like piRNA, snRNA and snoRNA. A comprehensive platform is needed to interrogate the full small RNA'ome, a prerequisite for down-stream data analysis. Results We present COMPASS, a comprehensive modular stand-alone platform for identifying and quantifying small RNAs from small RNA sequencing data. COMPASS contains prebuilt customizable standard RNA databases and sequence processing tools to enable turnkey basic small RNA analysis. We evaluated COMPASS against comparable existing tools on small RNA sequencing data set from serum samples of 12 healthy human controls, and COMPASS identified a greater diversity and abundance of small RNA molecules. Conclusion COMPASS is modular, stand-alone and integrates multiple customizable RNA databases and sequence processing tool and is distributed under the GNU General Public License free to non-commercial registered users at https://regepi.bwh.harvard.edu/circurna/ and the source code is available at https://github.com/cougarlj/COMPASS.

Corrigendum to “Functional segmentation of the hippocampus in the healthy human brain and in Alzheimer's disease” [Neuroimage 66 (2013) 28–35]

NeuroImage ◽  
2013 ◽  
Vol 83 ◽  
pp. 1109
Author(s):  
Mojtaba Zarei ◽  
Christian F. Beckmann ◽  
Maja A.A. Binnewijzend ◽  
Menno M. Schoonheim ◽  
Mohammad Ali Oghabian ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Healthy Human
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