cap analysis
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2022 ◽  
Vol 5 (4) ◽  
pp. e202101234
Author(s):  
Sonal Dahale ◽  
Jorge Ruiz-Orera ◽  
Jan Silhavy ◽  
Norbert Hübner ◽  
Sebastiaan van Heesch ◽  
...  

The role of alternative promoter usage in tissue-specific gene expression has been well established; however, its role in complex diseases is poorly understood. We performed cap analysis of gene expression (CAGE) sequencing from the left ventricle of a rat model of hypertension, the spontaneously hypertensive rat (SHR), and a normotensive strain, Brown Norway to understand the role of alternative promoter usage in complex disease. We identified 26,560 CAGE-defined transcription start sites in the rat left ventricle, including 1,970 novel cardiac transcription start sites. We identified 28 genes with alternative promoter usage between SHR and Brown Norway, which could lead to protein isoforms differing at the amino terminus between two strains and 475 promoter switching events altering the length of the 5′ UTR. We found that the shift in Insr promoter usage was significantly associated with insulin levels and blood pressure within a panel of HXB/BXH recombinant inbred rat strains, suggesting that hyperinsulinemia due to insulin resistance might lead to hypertension in SHR. Our study provides a preliminary evidence of alternative promoter usage in complex diseases.


2022 ◽  
Author(s):  
Hang Yang ◽  
Xing Yao ◽  
Hong Zhang ◽  
Chun Meng ◽  
Bharat B Biswal

Brain states can be characterized by recurring coactivation patterns (CAPs). Traditional CAP analysis is performed at the group-level, while the human brain is individualized and the functional connectome has shown the uniqueness as fingerprint. Whether stable individual CAPs could be obtained from a single fMRI scan and could individual CAPs improve the identification is unclear. An open dataset, the midnight scan club was used in this study to answer these questions. Four CAP states were identified at three distinct levels (group-, subject- and scan-level) separately, and the CAPs were then reconstructed for each scan. Identification rate and differential identifiability were used to evaluate the identification performance. Our results demonstrated that the individual CAPs were unstable when using a single scan. By maintaining high intra-subject similarity and inter-subject differences, subject-level CAPs achieved the best identification performance. Brain regions that contributed to the identifiability were mainly located in higher-order networks (e.g., frontal-parietal network). Besides, head motion reduced the intra-subject similarity, while its impact on identification rate was non-significant. Finally, a pipeline was developed to depict brain-behavior associations in dataset with few samples but dense sampling, and individualized CAP dynamics showed an above-chance level correlation with IQ.


2021 ◽  
Vol 8 (12) ◽  
pp. 172-181
Author(s):  
Rahmat Sutono ◽  
Harianto . ◽  
Imam Teguh Saptono

PT SH is a company that distributes veterinary medicinal products produced by Lallemand Animal Nutrition (France) and several products from other suppliers. This product from Lallemand is included in the feed additive class which functions to increase livestock productivity with better feed conversion. Competition in product sales in this group greatly affects the sales of feed additives for PT SH. Therefore, this study uses CAP and CSP analysis to analyze the marketing of PT SH, and analyzes the competition between PT SH and other companies in the sale of feed additives. CAP analysis consists of marketing strategy, tactics and values, while CSP analysis consists of customer demand, competitive situation, and variable factors. CAP analysis gives an average score of 2.82, this mid score indicates that the strategies and tactics used as well as the marketing value of PT SH need to be improved in order to increase PT SH's feed additive sales. CSP analysis gives an average score of 3.56, this fairly large score indicates that PT SH's competition with other companies is quite strong in the sale of feed additives. This requires PT SH to maintain quality, improve marketing strategy services to increase sales of feed additives, so that PT SH is not left behind by other companies. Keywords: CAP analysis, CSP analysis, Mix, Feed additive, Marketing.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260984
Author(s):  
Maria Paola Tramonti Fantozzi ◽  
Ugo Faraguna ◽  
Adrien Ugon ◽  
Gastone Ciuti ◽  
Andrea Pinna

The Cyclic Alternating Pattern (CAP) is composed of cycles of two different electroencephalographic features: an activation A-phase followed by a B-phase representing the background activity. CAP is considered a physiological marker of sleep instability. Despite its informative nature, the clinical applications remain limited as CAP analysis is a time-consuming activity. In order to overcome this limit, several automatic detection methods were recently developed. In this paper, two new dimensions were investigated in the attempt to optimize novel, efficient and automatic detection algorithms: 1) many electroencephalographic leads were compared to identify the best local performance, and 2) the global contribution of the concurrent detection across several derivations to CAP identification. The developed algorithms were tested on 41 polysomnographic recordings from normal (n = 8) and pathological (n = 33) subjects. In comparison with the visual CAP analysis as the gold standard, the performance of each algorithm was evaluated. Locally, the detection on the F4-C4 derivation showed the best performance in comparison with all other leads, providing practical suggestions of electrode montage when a lean and minimally invasive approach is preferable. A further improvement in the detection was achieved by a multi-trace method, the Global Analysis—Common Events, to be applied when several recording derivations are available. Moreover, CAP time and CAP rate obtained with these algorithms positively correlated with the ones identified by the scorer. These preliminary findings support efficient automated ways for the evaluation of the sleep instability, generalizable to both normal and pathological subjects affected by different sleep disorders.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaori Kato ◽  
Masato Tsutsui ◽  
Shingo Noguchi ◽  
Yukitoshi Iha ◽  
Keisuke Naito ◽  
...  

AbstractThe roles of endogenous nitric oxide (NO) derived from the entire NO synthases (NOSs) system have yet to be fully elucidated. We addressed this issue in mice in which all three NOS isoforms were deleted. Under basal conditions, the triple n/i/eNOSs−/− mice displayed significantly longer mean alveolar linear intercept length, increased alveolar destructive index, reduced lung elastic fiber content, lower lung field computed tomographic value, and greater end-expiratory lung volume as compared with wild-type (WT) mice. None of single NOS−/− or double NOSs−/− genotypes showed such features. These findings were observed in the triple n/i/eNOSs−/− mice as early as 4 weeks after birth. Cyclopaedic and quantitative comparisons of mRNA expression levels between the lungs of WT and triple n/i/eNOSs−/− mice by cap analysis of gene expression (CAGE) revealed that mRNA expression levels of three Wnt ligands and ten Wnt/β-catenin signaling components were significantly reduced in the lungs of triple n/i/eNOSs−/− mice. These results provide the first direct evidence that complete disruption of all three NOS genes results in spontaneous pulmonary emphysema in juvenile mice in vivo possibly through down-regulation of the Wnt/β-catenin signaling pathway, demonstrating a novel preventive role of the endogenous NO/NOS system in the occurrence of pulmonary emphysema.


2021 ◽  
Author(s):  
Ruslan Deviatiiarov ◽  
Anna Gams ◽  
Roman Syunyaev ◽  
Tatiana Tatarinova ◽  
Ramesh Singh ◽  
...  

Abstract A continuous increase in the prevalence of heart failure and the lack of adequate therapy highlight poor understanding of the underlying genetic regulatory mechanisms involved in heart failure pathogenesis. Growing evidence has demonstrated a significant contribution of non-coding genome regulatory elements towards transcriptomic changes in heart disease. Thus, there is a pressing need for a comprehensive resource of the human cardiac regulatory network in healthy and failing states. We applied cap analysis of gene expression sequencing to directly measure the expression of RNA associated with enhancers and promoters. Based on this data, we constructed the atlas of transcribed cardiac regulatory elements from 21 healthy and 10 failing (ischemic and non-ischemic cardiomyopathy) human hearts. In total, we have sequenced 109 samples from the left and right atria and ventricles, identifying 17,668 promoters and 14,920 enhancers associated with 14,519 genes. Leveraging this atlas, we provide insights into functional and structural regulatory changes between healthy and failing hearts. Healthy atria and ventricles had distinct pathway enrichment and transcription factor binding patterns, significantly remodeled by heart failure. Using the advantages of deep sequencing that allow effective analysis of cis-regulatory elements-derived RNA, we found that heart failure is associated with the expression of transcripts derived from alternative promoters and a specific set of transcribed enhancers. Furthermore, we identified a high prevalence of single nucleotide polymorphisms associated with cardiovascular diseases within the regulatory regions highlighting their importance in disease pathogenesis. This open-source atlas will serve the cardiovascular community to improve understanding cardiac regulatory network and facilitate the development of novel therapeutics.


2021 ◽  
Vol 22 (20) ◽  
pp. 10962
Author(s):  
Kouji Niidome ◽  
Ruri Taniguchi ◽  
Takeshi Yamazaki ◽  
Mayumi Tsuji ◽  
Kouichi Itoh ◽  
...  

We previously showed that the antiepileptic drug levetiracetam (LEV) inhibits microglial activation, but the mechanism remains unclear. The purpose of this study was to identify the target of LEV in microglial activity suppression. The mouse microglial BV-2 cell line, cultured in a ramified form, was pretreated with LEV and then treated with lipopolysaccharide (LPS). A comprehensive analysis of LEV targets was performed by cap analysis gene expression sequencing using BV-2 cells, indicating the transcription factors BATF, Nrf-2, FosL1 (Fra1), MAFF, and Spic as candidates. LPS increased AP-1 and Spic transcriptional activity, and LEV only suppressed AP-1 activity. FosL1, MAFF, and Spic mRNA levels were increased by LPS, and LEV only attenuated FosL1 mRNA expression, suggesting FosL1 as an LEV target. FosL1 protein levels were increased by LPS treatment and decreased by LEV pretreatment, similar to FosL1 mRNA levels. The FosL1 siRNA clearly suppressed the expression of TNFα and IL-1β. Pilocarpine-induced status epilepticus increased hippocampus FosL1 expression, along with inflammation. LEV treatment significantly suppressed FosL1 expression. Together, LEV reduces FosL1 expression and AP-1 activity in activated microglia, thereby suppressing neuroinflammation. LEV might be a candidate for the treatment of several neurological diseases involving microglial activation.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Luca Ducoli ◽  
Saumya Agrawal ◽  
Chung-Chau Hon ◽  
Jordan A. Ramilowski ◽  
Eliane Sibler ◽  
...  

Abstract Background The lymphatic and the blood vasculature are closely related systems that collaborate to ensure the organism’s physiological function. Despite their common developmental origin, they present distinct functional fates in adulthood that rely on robust lineage-specific regulatory programs. The recent technological boost in sequencing approaches unveiled long noncoding RNAs (lncRNAs) as prominent regulatory players of various gene expression levels in a cell-type-specific manner. Results To investigate the potential roles of lncRNAs in vascular biology, we performed antisense oligonucleotide (ASO) knockdowns of lncRNA candidates specifically expressed either in human lymphatic or blood vascular endothelial cells (LECs or BECs) followed by Cap Analysis of Gene Expression (CAGE-Seq). Here, we describe the quality control steps adopted in our analysis pipeline before determining the knockdown effects of three ASOs per lncRNA target on the LEC or BEC transcriptomes. In this regard, we especially observed that the choice of negative control ASOs can dramatically impact the conclusions drawn from the analysis depending on the cellular background. Conclusion In conclusion, the comparison of negative control ASO effects on the targeted cell type transcriptomes highlights the essential need to select a proper control set of multiple negative control ASO based on the investigated cell types.


Author(s):  
Matteo Maurizio Guerrini ◽  
Akiko Oguchi ◽  
Akari Suzuki ◽  
Yasuhiro Murakawa

2021 ◽  
Author(s):  
Teppei Matsui ◽  
Trung Quang Pham ◽  
Koji Jimura ◽  
Junichi Chikazoe

AbstractThe non-stationarity of resting-state brain activity has received increasing attention in recent years. Functional connectivity (FC) analysis with short sliding windows and coactivation pattern (CAP) analysis are two widely used methods for assessing the non-stationary characteristics of brain activity observed with functional magnetic resonance imaging (fMRI). However, whether these techniques adequately capture non-stationarity needs to be verified. In this study, we found that the results of CAP analysis were similar for real fMRI data and simulated stationary data with matching covariance structures and spectral contents. We also found that, for both the real and simulated data, CAPs were clustered into spatially heterogeneous modules. Moreover, for each of the modules in the real data, a spatially similar module was found in the simulated data. The present results suggest that care needs to be taken when interpreting observations drawn from CAP analysis as it does not necessarily reflect non-stationarity or a mixture of states in resting brain activity.


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