scholarly journals Epigenomic regulation of heart failure: integrating histone marks, long noncoding RNAs, and chromatin architecture

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1713 ◽  
Author(s):  
Timothy A. McKinsey ◽  
Thomas M. Vondriska ◽  
Yibin Wang
Keyword(s):  
Heart Failure ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Loss Of Function ◽  
Sequencing Technologies ◽  
Recent Developments ◽  
Non Coding Rnas ◽  
Epigenomic Regulation ◽  
Generation Sequencing ◽  
Epigenetic Processes

Epigenetic processes are known to have powerful roles in organ development across biology. It has recently been found that some of the chromatin modulatory machinery essential for proper development plays a previously unappreciated role in the pathogenesis of cardiac disease in adults. Investigations using genetic and pharmacologic gain- and loss-of-function approaches have interrogated the function of distinct epigenetic regulators, while the increased deployment of the suite of next-generation sequencing technologies have fundamentally altered our understanding of the genomic targets of these chromatin modifiers. Here, we review recent developments in basic and translational research that have provided tantalizing clues that may be used to unlock the therapeutic potential of the epigenome in heart failure. Additionally, we provide a hypothesis to explain how signal-induced crosstalk between histone tail modifications and long non-coding RNAs triggers chromatin architectural remodeling and culminates in cardiac hypertrophy and fibrosis.

scholarly journals Exploring the Roles of lncRNAs in GBM Pathophysiology and Their Therapeutic Potential

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2369
Author(s):  
Christian T. Stackhouse ◽  
G. Yancey Gillespie ◽  
Christopher D. Willey
Keyword(s):  
Therapeutic Potential ◽  
Therapy Resistance ◽  
Aberrant Expression ◽  
Chromatin Dynamics ◽  
The Past ◽  
Sequencing Technologies ◽  
Damage Response ◽  
Non Coding Rnas ◽  
Generation Sequencing ◽  
Recurrent Gbm

Glioblastoma (GBM) remains the most devastating primary central nervous system malignancy with a median survival of around 15 months. The past decades of research have not yielded significant advancements in the treatment of GBM. In that same time, a novel class of molecules, long non-coding RNAs (lncRNAs), has been found to play a multitude of roles in cancer and normal biology. The increased accessibility of next generation sequencing technologies and the advent of lncRNA-specific microarrays have facilitated the study of lncRNA etiology. Molecular and computational methods can be applied to predict lncRNA function. LncRNAs can serve as molecular decoys, scaffolds, super-enhancers, or repressors. These molecules can serve as phenotypic switches for GBM cells at the expression and/or epigenetic levels. LncRNAs can affect stemness/differentiation, proliferation, invasion, survival, DNA damage response, and chromatin dynamics. Aberrant expression of these transcripts may facilitate therapy resistance, leading to tumor recurrence. LncRNAs could serve as novel theragnostic or prognostic biomarkers in GBM and other cancers. RNA-based therapeutics may also be employed to target lncRNAs as a novel route of treatment for primary or recurrent GBM. In this review, we explore the roles of lncRNAs in GBM pathophysiology and posit their novel therapeutic potential for GBM.

scholarly journals Long Non-Coding RNA and Breast Cancer

2019 ◽  
Vol 18 ◽  
pp. 153303381984388 ◽  
Author(s):  
Tianzhu Zhang ◽  
Hui Hu ◽  
Ge Yan ◽  
Tangwei Wu ◽  
Shuiyi Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Biological Function ◽  
Tumor Development ◽  
Health Concern ◽  
Sequencing Technologies ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna ◽  
Generation Sequencing

Breast cancer, one of the most common diseases among women, is regarded as a heterogeneous and complicated disease that remains a major public health concern. Recently, owing to the development of next-generation sequencing technologies, long non-coding RNAs have received extensive attention. Numerous studies reveal that long non-coding RNAs are playing important roles in tumor development. Although the biological function and molecular mechanisms of long non-coding RNAs remain enigmatic, recent researchers have demonstrated that an array of long non-coding RNAs express abnormally in cancers, including breast cancer. Herein, we summarized the latest literature about long non-coding RNAs in breast cancer, with a particular focus on the multiple molecular roles of regulatory long non-coding RNAs that regulate cell proliferation, invasion, metastasis, and apoptosis.

scholarly journals IDENTIFICATION OF IN SILICO MIRNAS IN FOUR PLANT SPECIES FROM FABACEAE FAMILY

AGROFOR ◽  
2019 ◽  
Vol 3 (3) ◽  
Author(s):  
Bihter AVSAR ◽  
Danial ESMAEILI ALIABADI
Keyword(s):  
Glycine Max ◽  
In Silico ◽  
Biological Processes ◽  
Biotechnological Applications ◽  
Sequencing Technologies ◽  
Number Of Genes ◽  
Functional Context ◽  
Non Coding Rnas ◽  
Growth Development ◽  
Generation Sequencing

Plant microRNAs (miRNAs) are small non-coding RNAs, about 21-24 nucleotides,which have critical regulatory roles on growth, development, metabolic anddefense processes. Their identification, together with their targets, have gainedimportance in exploring their parts on functional context, providing a betterunderstanding of their regulatory roles in critical biological processes. With theadvent of next-generation sequencing technologies and newly developedbioinformatics tools, the identification of microRNA studies by computationalmethods has been increasing. In the presented study, we identified some putativemiRNAs for Cicer arietinum, Glycine max, Medicago truncatula and Phaseolusvulgaris genomes. We also provided the similarity between those organismsregarding common/different miRNAs availability throughout their genomes.According to the data, the highest similarity was found between Glycine max andPhaseolus vulgaris. We also investigated the potential targets of putativelyidentified miRNAs for each organism. We analyzed which miRNA families wereexpressed in silico. We also showed the representation (copy number of genes)profile of predicted putative miRNAs for each organism. Since most of the foodproducts and animal feeds consist of Fabaceae family members as it is mentionedabove, these findings might help to elucidate their metabolic and regulatorypathways to use them efficiently in biotechnological applications and breedingprograms.

scholarly journals Noncoding RNAs regulating cardiac muscle mass

2019 ◽  
Vol 127 (2) ◽  
pp. 633-644 ◽  
Author(s):  
Glenn D. Wadley ◽  
Séverine Lamon ◽  
Sarah E. Alexander ◽  
Julie R. McMullen ◽  
Bianca C. Bernardo
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiac Hypertrophy ◽  
Cardiac Muscle ◽  
Muscle Mass ◽  
Targeted Delivery ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
The Body ◽  
Circular Rnas

Noncoding RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) play roles in the development and homeostasis of nearly every tissue of the body, including the regulation of processes underlying heart growth. Cardiac hypertrophy can be classified as either physiological (beneficial heart growth) or pathological (detrimental heart growth), the latter of which results in impaired cardiac function and heart failure and is predictive of a higher incidence of death due to cardiovascular disease. Several miRNAs have a functional role in exercise-induced cardiac hypertrophy, while both miRNAs and lncRNAs are heavily involved in pathological heart growth and heart failure. The latter have the potential to act as an endogenous sponge RNA and interact with specific miRNAs to control cardiac hypertrophy, adding another level of complexity to our understanding of the regulation of cardiac muscle mass. In addition to tissue-specific effects, ncRNA-mediated tissue cross talk occurs via exosomes. In particular, miRNAs can be internalized in exosomes and secreted from various cardiac and vascular cell types to promote angiogenesis, as well as protection and repair of ischemic tissues. ncRNAs hold promising therapeutic potential to protect the heart against ischemic injury and aid in regeneration. Numerous preclinical studies have demonstrated the therapeutic potential of ncRNAs, specifically miRNAs, for the treatment of cardiovascular disease. Most of these studies employ antisense oligonucleotides to inhibit miRNAs of interest; however, off-target effects often limit their potential to be translated to the clinic. In this context, approaches using viral and nonviral delivery tools are promising means to provide targeted delivery in vivo.

scholarly journals 5-Methylcytosine and 5-Hydroxymethylcytosine Signatures Underlying Pediatric Cancers

Epigenomes ◽  
2019 ◽  
Vol 3 (2) ◽  
pp. 9 ◽  
Author(s):  
Shalu Jhanwar ◽  
Ajinkya Deogade
Keyword(s):  
Pediatric Cancer ◽  
Therapeutic Potential ◽  
The Past ◽  
Pediatric Cancers ◽  
Genome Wide ◽  
Recent Developments ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Shed Light

In addition to the genetic variations, recent evidence has shown that DNA methylation of both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) underlies the pathogenesis of pediatric cancer. Given the high mortality rate, there is an urgent need to study the mechanisms contributing to the pathogenicity of pediatric cancer. Over the past decades, next-generation sequencing (NGS) has enabled us to perform genome-wide screening to study the complex regulatory mechanisms of 5mC and 5hmC underlying pediatric tumorigenesis. To shed light on recent developments on pediatric cancer predisposition and tumor progression, here we discuss the role of both genome-wide and locus-specific dysregulation of 5mC and 5hmC in hematopoiesis malignancy and neuroblastoma, the most common types of pediatric cancer, together with their therapeutic potential.

scholarly journals Translational Bioinformatics for Diagnostic and Prognostic Prediction of Prostate Cancer in the Next-Generation Sequencing Era

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Jiajia Chen ◽  
Daqing Zhang ◽  
Wenying Yan ◽  
Dongrong Yang ◽  
Bairong Shen
Keyword(s):  
Prostate Cancer ◽  
Next Generation Sequencing ◽  
High Throughput Sequencing ◽  
Sequence Data ◽  
Cancer Biomarkers ◽  
Translational Bioinformatics ◽  
Next Generation ◽  
Sequencing Technologies ◽  
Recent Developments ◽  
Generation Sequencing

The discovery of prostate cancer biomarkers has been boosted by the advent of next-generation sequencing (NGS) technologies. Nevertheless, many challenges still exist in exploiting the flood of sequence data and translating them into routine diagnostics and prognosis of prostate cancer. Here we review the recent developments in prostate cancer biomarkers by high throughput sequencing technologies. We highlight some fundamental issues of translational bioinformatics and the potential use of cloud computing in NGS data processing for the improvement of prostate cancer treatment.

Kindler's Syndrome with Recurrent Neutropenia: Report of Two Cases from Saudi Arabia

2020 ◽  
Author(s):  
Yousef Binamer ◽  
Muzamil A. Chisti
Keyword(s):  
Autosomal Recessive ◽  
Common Mechanism ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Skin Atrophy ◽  
Whole Exome ◽  
Infancy And Childhood ◽  
Genetics And Genomics ◽  
New Feature ◽  
Generation Sequencing

AbstractKindler syndrome (KS) is a rare photosensitivity disorder with autosomal recessive mode of inheritance. It is characterized by acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. Besides these major features, many minor presentations have also been reported in the literature. We are reporting two cases with atypical features of the syndrome and a new feature of recurrent neutropenia. Whole exome sequencing analysis was done using next-generation sequencing which detected a homozygous loss-of-function (LOF) variant of FERMT1 in both patients. The variant is classified as a pathogenic variant as per the American College of Medical Genetics and Genomics guidelines. Homozygous LOF variants of FERMT1 are a common mechanism of KS and as such confirm the diagnosis of KS in our patients even though the presentation was atypical.

The Medicinal Chemistry of Therapeutic Peptides: Recent Developments in Synthesis and Design Optimizations

2019 ◽  
Vol 26 (13) ◽  
pp. 2330-2355 ◽  
Author(s):  
Anutthaman Parthasarathy ◽  
Sasikala K. Anandamma ◽  
Karunakaran A. Kalesh
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
The Past ◽  
Recombinant Production ◽  
Tremendous Progress ◽  
Recent Developments ◽  
Therapeutic Peptides ◽  
Development Processes ◽  
Delivery Strategies

Peptide therapeutics has made tremendous progress in the past decade. Many of the inherent weaknesses of peptides which hampered their development as therapeutics are now more or less effectively tackled with recent scientific and technological advancements in integrated drug discovery settings. These include recent developments in synthetic organic chemistry, high-throughput recombinant production strategies, highresolution analytical methods, high-throughput screening options, ingenious drug delivery strategies and novel formulation preparations. Here, we will briefly describe the key methodologies and strategies used in the therapeutic peptide development processes with selected examples of the most recent developments in the field. The aim of this review is to highlight the viable options a medicinal chemist may consider in order to improve a specific pharmacological property of interest in a peptide lead entity and thereby rationally assess the therapeutic potential this class of molecules possesses while they are traditionally (and incorrectly) considered ‘undruggable’.

The Influence of Memory-Aware Computation on Distributed BLAST

2019 ◽  
Vol 14 (2) ◽  
pp. 157-163
Author(s):  
Majid Hajibaba ◽  
Mohsen Sharifi ◽  
Saeid Gorgin
Keyword(s):  
Search Time ◽  
Genomic Research ◽  
Local Alignment ◽  
Negative Effects ◽  
Sequencing Technologies ◽  
Percent Improvement ◽  
Fast Processing ◽  
Search Tool ◽  
Memory Awareness ◽  
Generation Sequencing

Background: One of the pivotal challenges in nowadays genomic research domain is the fast processing of voluminous data such as the ones engendered by high-throughput Next-Generation Sequencing technologies. On the other hand, BLAST (Basic Local Alignment Search Tool), a longestablished and renowned tool in Bioinformatics, has shown to be incredibly slow in this regard. Objective: To improve the performance of BLAST in the processing of voluminous data, we have applied a novel memory-aware technique to BLAST for faster parallel processing of voluminous data. Method: We have used a master-worker model for the processing of voluminous data alongside a memory-aware technique in which the master partitions the whole data in equal chunks, one chunk for each worker, and consequently each worker further splits and formats its allocated data chunk according to the size of its memory. Each worker searches every split data one-by-one through a list of queries. Results: We have chosen a list of queries with different lengths to run insensitive searches in a huge database called UniProtKB/TrEMBL. Our experiments show 20 percent improvement in performance when workers used our proposed memory-aware technique compared to when they were not memory aware. Comparatively, experiments show even higher performance improvement, approximately 50 percent, when we applied our memory-aware technique to mpiBLAST. Conclusion: We have shown that memory-awareness in formatting bulky database, when running BLAST, can improve performance significantly, while preventing unexpected crashes in low-memory environments. Even though distributed computing attempts to mitigate search time by partitioning and distributing database portions, our memory-aware technique alleviates negative effects of page-faults on performance.

scholarly journals Investigation of long non-coding RNAs as regulatory players of grapevine response to powdery and downy mildew infection

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Garima Bhatia ◽  
Santosh K. Upadhyay ◽  
Anuradha Upadhyay ◽  
Kashmir Singh
Keyword(s):  
Downy Mildew ◽  
Plasmopara Viticola ◽  
Defense Responses ◽  
Protein Coding ◽  
Functional Roles ◽  
Real Time Quantitative Pcr ◽  
Transcriptional Reprogramming ◽  
Sequencing Technologies ◽  
Non Coding Rnas ◽  
Fungal Phytopathogens

Abstract Background Long non-coding RNAs (lncRNAs) are regulatory transcripts of length > 200 nt. Owing to the rapidly progressing RNA-sequencing technologies, lncRNAs are emerging as considerable nodes in the plant antifungal defense networks. Therefore, we investigated their role in Vitis vinifera (grapevine) in response to obligate biotrophic fungal phytopathogens, Erysiphe necator (powdery mildew, PM) and Plasmopara viticola (downy mildew, DM), which impose huge agro-economic burden on grape-growers worldwide. Results Using computational approach based on RNA-seq data, 71 PM- and 83 DM-responsive V. vinifera lncRNAs were identified and comprehensively examined for their putative functional roles in plant defense response. V. vinifera protein coding sequences (CDS) were also profiled based on expression levels, and 1037 PM-responsive and 670 DM-responsive CDS were identified. Next, co-expression analysis-based functional annotation revealed their association with gene ontology (GO) terms for ‘response to stress’, ‘response to biotic stimulus’, ‘immune system process’, etc. Further investigation based on analysis of domains, enzyme classification, pathways enrichment, transcription factors (TFs), interactions with microRNAs (miRNAs), and real-time quantitative PCR of lncRNAs and co-expressing CDS pairs suggested their involvement in modulation of basal and specific defense responses such as: Ca2+-dependent signaling, cell wall reinforcement, reactive oxygen species metabolism, pathogenesis related proteins accumulation, phytohormonal signal transduction, and secondary metabolism. Conclusions Overall, the identified lncRNAs provide insights into the underlying intricacy of grapevine transcriptional reprogramming/post-transcriptional regulation to delay or seize the living cell-dependent pathogen growth. Therefore, in addition to defense-responsive genes such as TFs, the identified lncRNAs can be further examined and leveraged to candidates for biotechnological improvement/breeding to enhance fungal stress resistance in this susceptible fruit crop of economic and nutritional importance.

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