scholarly journals HBP: an integrative and flexible pipeline for the interaction analysis of Hi-C dataset

2016 ◽  
Author(s):  
Chao He ◽  
Ping Li ◽  
Minglei Shi ◽  
Yan Zhang ◽  
Bingyu Ye ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Molecular Mechanisms ◽  
Gene Expression Regulation ◽  
Interaction Analysis ◽  
Rapid Development ◽  
3D Structure ◽  
Biological Significance ◽  
Sequencing Data ◽  
Chromatin Interactions ◽  
Wide Range

AbstractBackgroundThe spatial organization of interphase chromatin in the nucleus play an important role in gene expression regulation and function. With the rapid development of revolutionized chromosome conformation capture technology and its genome-wide derivatives such as Hi-C, investigation of the genome folding becomes more efficient and convenient. How to robustly deal with these massive datasets and infer accurate 3D model and within-nucleus compartmentalization of chromosomes becomes a new challenge.ResultThe implemented pipeline HBP (Hi-C BED file analysis Pipeline) integrates existing pipelines focusing on individual steps of Hi-C data processing into an all-in-one package with adjustable parameters to infer the consensus 3D structure of genome from raw Hi-C sequencing data. What’s more, HBP could assign statistical confidence estimation for chromatin interactions, and clustering interaction loci according to enrichment tracks or topological structure automatically.ConclusionThe freely available HBP is an optimized and flexible pipeline for analyzing the folding of whole chromosome and interactions between some specific sites from the Hi-C raw sequencing reads to the partially processed datasets. The other complex genetic and epigenetic datasets from public sources such as GWAS, ENCODE consortiums etc. will also easily be integrated into HBP, hence the final output results of HBP could provide a comprehensive in-depth understanding for the specific chromatin interactions, potential molecular mechanisms and biological significance. We believe that HBP is a reliable tool for the rapidly analysis of Hi-C data and will be very useful for a wide range of researchers, particularly those who lack of background in computational biology. HBP is freely accessible at https://github.com/hechao0407/HBP/blob/master/HBP_1.0.tar.gz.

scholarly journals High throughput sequencing unravels tomato-pathogen interactions towards a sustainable plant breeding

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Maria Doroteia Campos ◽  
Maria do Rosário Félix ◽  
Mariana Patanita ◽  
Patrick Materatski ◽  
Carla Varanda
Keyword(s):  
Plant Breeding ◽  
High Throughput ◽  
Plant Pathogen ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Molecular Networks ◽  
Sequencing Data ◽  
Sources Of Resistance ◽  
Tomato Plants ◽  
Wide Range

AbstractTomato (Solanum lycopersicum) is one of the most economically important vegetables throughout the world. It is one of the best studied cultivated dicotyledonous plants, often used as a model system for plant research into classical genetics, cytogenetics, molecular genetics, and molecular biology. Tomato plants are affected by different pathogens such as viruses, viroids, fungi, oomycetes, bacteria, and nematodes, that reduce yield and affect product quality. The study of tomato as a plant-pathogen system helps to accelerate the discovery and understanding of the molecular mechanisms underlying disease resistance and offers the opportunity of improving the yield and quality of their edible products. The use of functional genomics has contributed to this purpose through both traditional and recently developed techniques, that allow the identification of plant key functional genes in susceptible and resistant responses, and the understanding of the molecular basis of compatible interactions during pathogen attack. Next-generation sequencing technologies (NGS), which produce massive quantities of sequencing data, have greatly accelerated research in biological sciences and offer great opportunities to better understand the molecular networks of plant–pathogen interactions. In this review, we summarize important research that used high-throughput RNA-seq technology to obtain transcriptome changes in tomato plants in response to a wide range of pathogens such as viruses, fungi, bacteria, oomycetes, and nematodes. These findings will facilitate genetic engineering efforts to incorporate new sources of resistance in tomato for protection against pathogens and are of major importance for sustainable plant-disease management, namely the ones relying on the plant’s innate immune mechanisms in view of plant breeding.

scholarly journals Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Huifen Cao ◽  
Dongyang Xu ◽  
Ye Cai ◽  
Xueer Han ◽  
Lu Tang ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Biological Significance ◽  
Genotoxic Stress ◽  
Cellular Adhesion ◽  
Negative Regulator ◽  
Chromatin Interactions ◽  
Multiple Genes ◽  
A Genome ◽  
Hidden Layer

Abstract Background The majority of the human genome is transcribed in the form of long non-coding (lnc) RNAs. While these transcripts have attracted considerable interest, their molecular mechanisms of function and biological significance remain controversial. One of the main reasons behind this lies in the significant challenges posed by lncRNAs requiring the development of novel methods and concepts to unravel their functionality. Existing methods often lack cross-validation and independent confirmation by different methodologies and therefore leave significant ambiguity as to the authenticity of the outcomes. Nonetheless, despite all the caveats, it appears that lncRNAs may function, at least in part, by regulating other genes via chromatin interactions. Therefore, the function of a lncRNA could be inferred from the function of genes it regulates. In this work, we present a genome-wide functional annotation strategy for lncRNAs based on identification of their regulatory networks via the integration of three distinct types of approaches: co-expression analysis, mapping of lncRNA-chromatin interactions, and assaying molecular effects of lncRNA knockdowns obtained using an inducible and highly specific CRISPR/Cas13 system. Results We applied the strategy to annotate 407 very long intergenic non-coding (vlinc) RNAs belonging to a novel widespread subclass of lncRNAs. We show that vlincRNAs indeed appear to regulate multiple genes encoding proteins predominantly involved in RNA- and development-related functions, cell cycle, and cellular adhesion via a mechanism involving proximity between vlincRNAs and their targets in the nucleus. A typical vlincRNAs can be both a positive and negative regulator and regulate multiple genes both in trans and cis. Finally, we show vlincRNAs and their regulatory networks potentially represent novel components of DNA damage response and are functionally important for the ability of cancer cells to survive genotoxic stress. Conclusions This study provides strong evidence for the regulatory role of the vlincRNA class of lncRNAs and a potentially important role played by these transcripts in the hidden layer of RNA-based regulation in complex biological systems.

scholarly journals STAT5-mediated chromatin interactions in superenhancers activate IL-2 highly inducible genes: Functional dissection of the Il2ra gene locus

2017 ◽  
Vol 114 (46) ◽  
pp. 12111-12119 ◽  
Author(s):  
Peng Li ◽  
Suman Mitra ◽  
Rosanne Spolski ◽  
Jangsuk Oh ◽  
Wei Liao ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Binding Sites ◽  
Gene Editing ◽  
Interaction Analysis ◽  
Chromatin Interaction ◽  
Sequencing Data ◽  
Chromatin Interactions ◽  
Normal Gene ◽  
Inducible Genes

Cytokines critically control immune responses, but how regulatory programs are altered to allow T cells to differentially respond to distinct cytokine stimuli remains poorly understood. Here, we have globally analyzed enhancer elements bound by IL-2–activated STAT5 and IL-21–activated STAT3 in T cells and identified Il2ra as the top-ranked gene regulated by an IL-2–activated STAT5-bound superenhancer and one of the top genes regulated by STAT3-bound superenhancers. Moreover, we found that STAT5 binding was rapidly superenriched at genes highly induced by IL-2 and that IL-2–activated STAT5 binding induces new and augmented chromatin interactions within superenhancer-containing genes. Based on chromatin interaction analysis by paired-end tag (ChIA-PET) sequencing data, we used CRISPR-Cas9 gene editing to target three of the STAT5 binding sites within the Il2ra superenhancer in mice. Each mutation decreased STAT5 binding and altered IL-2–induced Il2ra gene expression, revealing that individual elements within the superenhancer were not functionally redundant and that all were required for normal gene expression. Thus, we demonstrate cooperative utilization of superenhancer elements to optimize gene expression and show that STAT5 mediates IL-2–induced chromatin looping at superenhancers to preferentially regulate highly inducible genes, thereby providing new insights into the mechanisms underlying cytokine-dependent superenhancer function.

scholarly journals Plant Long Noncoding RNAs: New Players in the Field of Post-Transcriptional Regulations

2021 ◽  
Vol 7 (1) ◽  
pp. 12
Author(s):  
Camille Fonouni-Farde ◽  
Federico Ariel ◽  
Martin Crespi
Keyword(s):  
Gene Expression ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Gene Expression Regulation ◽  
Large Fraction ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Genomic Research ◽  
Protein Coding ◽  
Wide Range

The first reference to the “C-value paradox” reported an apparent imbalance between organismal genome size and morphological complexity. Since then, next-generation sequencing has revolutionized genomic research and revealed that eukaryotic transcriptomes contain a large fraction of non-protein-coding components. Eukaryotic genomes are pervasively transcribed and noncoding regions give rise to a plethora of noncoding RNAs with undeniable biological functions. Among them, long noncoding RNAs (lncRNAs) seem to represent a new layer of gene expression regulation, participating in a wide range of molecular mechanisms at the transcriptional and post-transcriptional levels. In addition to their role in epigenetic regulation, plant lncRNAs have been associated with the degradation of complementary RNAs, the regulation of alternative splicing, protein sub-cellular localization, the promotion of translation and protein post-translational modifications. In this review, we report and integrate numerous and complex mechanisms through which long noncoding transcripts regulate post-transcriptional gene expression in plants.

scholarly journals Evolution of Genome-Organizing Long Non-coding RNAs in Metazoans

2020 ◽  
Vol 11 ◽  
Author(s):  
América Ramírez-Colmenero ◽  
Katarzyna Oktaba ◽  
Selene L. Fernandez-Valverde
Keyword(s):  
Spatial Organization ◽  
Gene Expression Regulation ◽  
Dimensional Space ◽  
Functional Characterization ◽  
Three Dimensional ◽  
Protein Coding ◽  
Chromatin Interactions ◽  
Non Coding Rnas ◽  
Regulatory Functions ◽  
Three Dimensional Space

Long non-coding RNAs (lncRNAs) have important regulatory functions across eukarya. It is now clear that many of these functions are related to gene expression regulation through their capacity to recruit epigenetic modifiers and establish chromatin interactions. Several lncRNAs have been recently shown to participate in modulating chromatin within the spatial organization of the genome in the three-dimensional space of the nucleus. The identification of lncRNA candidates is challenging, as it is their functional characterization. Conservation signatures of lncRNAs are different from those of protein-coding genes, making identifying lncRNAs under selection a difficult task, and the homology between lncRNAs may not be readily apparent. Here, we review the evidence for these higher-order genome organization functions of lncRNAs in animals and the evolutionary signatures they display.

scholarly journals Network-based method for regions with statistically frequent interchromosomal interactions at single-cell resolution

2020 ◽  
Vol 21 (S14) ◽  
Author(s):  
Chanaka Bulathsinghalage ◽  
Lu Liu
Keyword(s):  
Single Cell ◽  
Computational Methods ◽  
Spatial Organization ◽  
Gene Expression Regulation ◽  
Statistical Tests ◽  
Single Cells ◽  
Search Space ◽  
Computational Method ◽  
Frequency Information ◽  
Chromatin Interactions

Abstract Background Chromosome conformation capture-based methods, especially Hi-C, enable scientists to detect genome-wide chromatin interactions and study the spatial organization of chromatin, which plays important roles in gene expression regulation, DNA replication and repair etc. Thus, developing computational methods to unravel patterns behind the data becomes critical. Existing computational methods focus on intrachromosomal interactions and ignore interchromosomal interactions partly because there is no prior knowledge for interchromosomal interactions and the frequency of interchromosomal interactions is much lower while the search space is much larger. With the development of single-cell technologies, the advent of single-cell Hi-C makes interrogating the spatial structure of chromatin at single-cell resolution possible. It also brings a new type of frequency information, the number of single cells with chromatin interactions between two disjoint chromosome regions. Results Considering the lack of computational methods on interchromosomal interactions and the unsurprisingly frequent intrachromosomal interactions along the diagonal of a chromatin contact map, we propose a computational method dedicated to analyzing interchromosomal interactions of single-cell Hi-C with this new frequency information. To the best of our knowledge, our proposed tool is the first to identify regions with statistically frequent interchromosomal interactions at single-cell resolution. We demonstrate that the tool utilizing networks and binomial statistical tests can identify interesting structural regions through visualization, comparison and enrichment analysis and it also supports different configurations to provide users with flexibility. Conclusions It will be a useful tool for analyzing single-cell Hi-C interchromosomal interactions.

scholarly journals The 3D Genome: From Structure to Function

2021 ◽  
Vol 22 (21) ◽  
pp. 11585
Author(s):  
Tapan Kumar Mohanta ◽  
Awdhesh Kumar Mishra ◽  
Ahmed Al-Harrasi
Keyword(s):  
Spatial Organization ◽  
Rapid Development ◽  
3D Structure ◽  
Three Dimensional ◽  
Genome Chromosome ◽  
3D Genome ◽  
Topologically Associated Domains ◽  
Functional Part ◽  
A Cell ◽  
Microscopy Techniques

The genome is the most functional part of a cell, and genomic contents are organized in a compact three-dimensional (3D) structure. The genome contains millions of nucleotide bases organized in its proper frame. Rapid development in genome sequencing and advanced microscopy techniques have enabled us to understand the 3D spatial organization of the genome. Chromosome capture methods using a ligation approach and the visualization tool of a 3D genome browser have facilitated detailed exploration of the genome. Topologically associated domains (TADs), lamin-associated domains, CCCTC-binding factor domains, cohesin, and chromatin structures are the prominent identified components that encode the 3D structure of the genome. Although TADs are the major contributors to 3D genome organization, they are absent in Arabidopsis. However, a few research groups have reported the presence of TAD-like structures in the plant kingdom.

scholarly journals DNA Methylation Status in Cancer Disease: Modulations by Plant-Derived Natural Compounds and Dietary Interventions

Biomolecules ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 289 ◽  
Author(s):  
Karin Jasek ◽  
Peter Kubatka ◽  
Marek Samec ◽  
Alena Liskova ◽  
Karel Smejkal ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Rapid Development ◽  
Methylation Status ◽  
Dna Methyltransferases ◽  
Epigenetic Mechanism ◽  
Preclinical Research ◽  
Gene Expressions ◽  
Wide Range

The modulation of the activity of DNA methyltransferases (DNMTs) represents a crucial epigenetic mechanism affecting gene expressions or DNA repair mechanisms in the cells. Aberrant modifications in the function of DNMTs are a fundamental event and part of the pathogenesis of human cancer. Phytochemicals, which are biosynthesized in plants in the form of secondary metabolites, represent an important source of biomolecules with pleiotropic effects and thus provide a wide range of possible clinical applications. It is well documented that phytochemicals demonstrate significant anticancer properties, and in this regard, rapid development within preclinical research is encouraging. Phytochemicals affect several epigenetic molecular mechanisms, including DNA methylation patterns such as the hypermethylation of tumor-suppressor genes and the global hypomethylation of oncogenes, that are specific cellular signs of cancer development and progression. This review will focus on the latest achievements in using plant-derived compounds and plant-based diets targeting epigenetic regulators and modulators of gene transcription in preclinical and clinical research in order to generate novel anticancer drugs as sensitizers for conventional therapy or compounds suitable for the chemoprevention clinical setting in at-risk individuals. In conclusion, indisputable anticancer activities of dietary phytochemicals linked with proper regulation of DNA methylation status have been described. However, precisely designed and well-controlled clinical studies are needed to confirm their beneficial epigenetic effects after long-term consumption in humans.

Cancer Proteomics: New Horizons and Insights into Therapeutic Applications

2020 ◽  
Vol 17 ◽  
Author(s):  
Perumal Subramaniana ◽  
Jaime Jacqueline Jayapalan ◽  
Puteri Shafinaz Abdul-Rahmanb
Keyword(s):  
Molecular Mechanisms ◽  
Rapid Development ◽  
New Horizons ◽  
Cancer Management ◽  
Proteomic Approach ◽  
Cancer Proteomics ◽  
Therapeutic Outcomes ◽  
A Genome ◽  
Highly Sensitive ◽  
Dimensional Electrophoresis

A proteome is an efficient rendition of a genome, unswervingly controlling various cancer processes. Molecular mechanisms of several cancer processes have been unraveled by proteomic approach. Thus far, numerous tumors of diverse status have been investigated by two-dimensional electrophoresis. Numerous biomarkers have been recognized and precise categorization of apparent lesions has led to the timely detection of various cancers in persons at peril. Currently used pioneering approaches and technologies in proteomics have led to highly sensitive assays of cancer biomarkers and improved the early diagnosis of various cancers. The discovery of novel and definite biomarker signatures further widened our perceptive of the disease and novel potent drugs for efficient and aimed therapeutic outcomes in persistent cancers have emerged. However, a major limitation, even today, of proteomics is resolving and quantifying the proteins of low abundance. Despite the rapid development of proteomic technologies and their applications in cancer management, annulling the shortcomings of present proteomic technologies and development of better methods are still desirable. The main objectives of this review are to discuss the developing aspects, merits and demerits of pharmacoproteomics, redox proteomics, novel approaches and therapies being used for various types of cancer based on proteome studies.

1,4-Diazepines: A Review on Synthesis, Reactions and Biological Significance

2019 ◽  
Vol 16 (5) ◽  
pp. 709-729 ◽  
Author(s):  
Muhammad A. Rashid ◽  
Aisha Ashraf ◽  
Sahibzada S. Rehman ◽  
Shaukat A. Shahid ◽  
Adeel Mahmood ◽  
...  
Keyword(s):  
Biological Activities ◽  
Biological Significance ◽  
Biological Evaluation ◽  
Wide Range ◽  
Pharmaceutical Industries ◽  
Biological Aspects ◽  
Synthetic Routes ◽  
Biological Attributes ◽  
Synthesis Reactions ◽  
Potential Use

Background:1,4-Diazepines are two nitrogen containing seven membered heterocyclic compounds and associated with a wide range of biological activities. Due to its medicinal importance, scientists are actively involved in the synthesis, reactions and biological evaluation of 1,4-diazepines since number of decades.Objective:The primary purpose of this review is to discuss the synthetic schemes and reactivity of 1,4- diazepines. This article also describes biological aspects of 1,4-diazepine derivatives, that can be usefully exploited for the pharmaceutical sector.Conclusion:This review summarizes the abundant literature on synthetic routes, chemical reactions and biological attributes of 1,4-diazepine derivatives. We concluded that 1,4-diazepines have significant importance due to their biological activities like antipsychotic, anxiolytic, anthelmintic, anticonvulsant, antibacterial, antifungal and anticancer. 1,4-diazepine derivatives with significant biological activities could be explored for potential use in the pharmaceutical industries.

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