Current article: Mechanism of CAV and CAVIN Family Genes in Acute Lung Injury based on DeepGene

Author(s): Changsheng LiHexiao TangZetian YangZheng TangNitao ChengJingyu Huang* and Xuefeng Zhou*

Background: The fatality rate of acute lung injury (ALI) is as high as 40% to 60%. Although various factors, such as sepsis, trauma, pneumonia, burns, blood transfusion, cardiopulmonary bypass, and pancreatitis, can induce ALI, patients with these risk factors will eventually develop ALI. The rate of developing ALI is not high, and the outcomes of ALI patients vary, indicating that it is related to genetic differences between individuals. In a previous study, we found multiple functions of cavin-2 in lung function. In addition, many other studies have revealed that CAV1 is a critical regulator of lung injury. Due to the strong relationship between cavin-2 and CAV1, we suspect that cavin-2 is also associated with ALI. Furthermore, we are curious about the role of the CAV family and Cavin family genes in ALI.

Methods: To reveal the mechanism of CAV and CAVIN family genes in ALI, we propose Deepgene to predict whether CAV and CAVIN family genes are associated with ALI. This method constructs a gene interaction network and extracts gene expression in 84 tissues. We divided these features into two groups and used two network encoders to encode and learn the features.

Results: Compared with DNN, GBDT, RF and KNN, the AUC of Deepgene increased by 7.89%, 16.84%, 20.19% and 32.01%, respectively. The AUPR scores increased by 8.05%, 15.58%, 22.56% and 23.34%. DeepGENE shows that CAVIN-1, CAVIN-2, CAVIN-3 and CAV2 are related to ALI.

Conclusion: DeepGENE is a reliable method for identifying acute lung injury-related genes. Multiple CAV and CAVIN family genes are associated with acute lung injury-related genes through multiple pathways and gene functions.

Download and read: https://bit.ly/3PCqp5u

TESTIMONIAL BY VALERIA SORRENTI!

Louis Lteif

Contributed Article: “Dietary Compounds, Epigenetic Modifications and Metabolic Diseases

EDITOR’S CHOICE – Integration of DNA Methylation Data and Gene Expression Data for Prostate Adenocarcinoma: A Proof of Concept – Current Bioinformatics

Journal: Current Bioinformatics

Author(s): Arpit Singh, Razia Rahman, Yasha Hasija

Graphical Abstract:

 

Abstract:

Background: Epigenetics is gaining rapid recognition as it accounts for heritable changes that do not involve changes in the coding sequence, but influences change in gene expressions. DNA methylation is the most extensively studied epigenetic mechanism and has been observed to play a significant role in gene regulation and silencing process.

Objective: In our present work, we focused on understanding the relationship between DNA methylation and gene expression. As a proof of concept, Prostate Adenocarcinoma (PRAD), the second leading cause of death in men, was extensively studied to unravel the epigenetic abnormalities associated with disease pathogenesis which may contribute to better diagnosis and prevention of prostate cancer.

Method: DNA methylation data (level 1) and Gene expression data (level 3) was taken from The Cancer Genome Atlas (TCGA). A total of 36 samples comprising of 18 normal samples and 18 tumor samples were collected from a batch of 184 and matched with tumor samples and normal samples, respectively. The differentially methylated regions were identified and statistical analysis was carried out for the gene expression data amongst the normal and tumor samples. Further, functional enrichment analysis and pathway analysis were carried out for the filtered genes.

Results: Our analysis indicated 453 differentially methylated regions with p-value < 0.05, FDR (false discovery rate) value < 0.05 and beta value (methylation) > 0.2. The integration of gene expression data with methylation data resulted in 180 significant correlations from which 112 genes were filtered under stringent conditions. Out of these 112 genes, 74 genes were filtered through visual inspection of results and their functional enrichment analysis resulted in total 27 clusters with a maximum enrichment score of ~1.86.

Conclusion: The genes “GSTP1” and “FGFR2” were present in our prioritized filtered significant correlations, and it was discovered that these genes were known to play a primary role in prostate cancer pathway and progression. Therefore, this approach may help to prioritize other novel genes and suggest their involvement in the prostate cancer pathway

 

Read more here: http://www.eurekaselect.com/151165

Podcast: Bone microRNAs and Aging

Author(s): Janja Marc, Barbara Ostanek, Tilen Kranjc

For article details, visit: http://www.eurekaselect.com/node/149728/article/bone-micrornas-and-aging

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Most Accessed Article – “Tet-On Systems For Doxycycline-inducible Gene Expression”

Journal: Current Gene Therapy

Author(s): Atze T. Das, Liliane Tenenbaum and Ben Berkhout

cgt

Abstract

The tetracycline-controlled Tet-Off and Tet-On gene expression systems are used to regulate the activity of genes in eukaryotic cells in diverse settings, varying from basic biological research to biotechnology and gene therapy applications. These systems are based on regulatory elements that control the activity of the tetracycline-resistance operon in bacteria. The Tet-Off system allows silencing of gene expression by administration of tetracycline (Tc) or tetracycline-derivatives like doxycycline (dox), whereas the Tet-On system allows activation of gene expression by dox. Since the initial design and construction of the original Tet-system, these bacterium-derived systems have been significantly improved for their function in eukaryotic cells. We here review how a dox-controlled HIV-1 variant was designed and used to greatly improve the activity and dox-sensitivity of the rtTA transcriptional activator component of the Tet-On system. These optimized rtTA variants require less dox for activation, which will reduce side effects and allow gene control in tissues where a relatively low dox level can be reached, such as the brain.

To access the article, please visit: http://benthamscience.com/journals/current-gene-therapy/volume/16/issue/3/page/156/

Meditation can result in important gene expression changes

meditation

Gene expression:

Gene expression refers to the process of getting information from a gene used in the synthesis of a functional gene product such as proteins.

Present Study:

Researchers have found that eight hours of mindfulness/calmness of mind practice, i.e. meditation, results in a range of many genetic expression and molecular differences such as changed levels of gene-regulating machinery and decreased levels of pro-inflammatory genes; RIPK2 and COX2 as well as several histone deacetylase (HDAC) genes, helping in faster recovery from a stressful situation.

“To the best of our knowledge, this is the first paper that shows rapid alterations in gene expression within subjects associated with mindfulness meditation practice,” noted study author Richard J. Davidson, founder of the Center for Investigating Healthy Minds and the William James and Vilas Professor of Psychology and Psychiatry at the University of Wisconsin-Madison.

“Most interestingly, the changes were observed in genes that are the current targets of anti-inflammatory and analgesic drugs,” added Perla Kaliman, first author of the article and a researcher at the Institute of Biomedical Research of Barcelona, Spain (IIBB-CSIC-IDIBAPS), where the molecular analyses were conducted.

Sources:

Study reveals gene expression changes with meditation – UW-Madison (http://goo.gl/2q9dbH)

Perla Kaliman et al. (2013). Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators Psychoneuroendocrinology DOI: 10.1016/j.psyneuen.2013.11.004

[Source: saypeople.com]

Current Drug Targets

Schematic of microRNA transfer by exosomes. miRNAs were overexpressed via transfected with miRNAs expression vector and then microRNAs are selectively incorporated into the intraluminal vesicles of a multivesicular bodies (MVBs). Exosomes containing miRNAs are derived from the MVBs and could be released into the extracellular environment by either fusion of MVBs with the cell surface or budding pathway. Exosomes may bind to the plasma membrane of a target cell. Recruited exosomes may either fuse directly with the plasma membrane or first be endocytosed and then fuse with the delimiting membrane of an endocytic compartment. Both pathways result in the delivery of the exosomal miRNAs to the cytoplasm of the target cell where it may associate with and silence corresponding mRNA.

Schematic of microRNA transfer by exosomes
Schematic of microRNA transfer by exosomes

 

The maturation process of miRNAs. In nucleus, the RNA Pol II transcribes pri-miRNA and be cleaved by DROSHA/DGCR8 complex to form pre-miRNA. Then the pre-miRNA will be transported to the cytoplasm by Exportin-5, where they are further processed by the RNase III endonuclease DICER to form the mature single stranded miRNA. Then the strand will enter the RNA induced silencing complex (RISC) to suppress the target mRNA either by translational repression (Partial complementarity) or by target degradation (complete complementarity).

The maturation process of miRNAs
The maturation process of miRNAs

 

Selected miRNAs reportedly involved in UV-induced skin response:

Selected miRNAs  in UV-induced skin response
Selected miRNAs in UV-induced skin response

 

Biosynthesis of miRNAs and their role in Pancreatic cancer:

Biosynthesis of miRNAs and their role in Pancreatic cancer
Biosynthesis of miRNAs and their role in Pancreatic cancer

 

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