Asymmetron: a toolkit for the identification of strand asymmetry patterns in biological sequences

Abstract DNA strand asymmetries can have a major effect on several biological functions, including replication, transcription and transcription factor binding. As such, DNA strand asymmetries and mutational strand bias can provide information about biological function. However, a versatile tool to explore this does not exist. Here, we present Asymmetron, a user-friendly computational tool that performs statistical analysis and visualizations for the evaluation of strand asymmetries. Asymmetron takes as input DNA features provided with strand annotation and outputs strand asymmetries for consecutive occurrences of a single DNA feature or between pairs of features. We illustrate the use of Asymmetron by identifying transcriptional and replicative strand asymmetries of germline structural variant breakpoints. We also show that the orientation of the binding sites of 45% of human transcription factors analyzed have a significant DNA strand bias in transcribed regions, that is also corroborated in ChIP-seq analyses, and is likely associated with transcription. In summary, we provide a novel tool to assess DNA strand asymmetries and show how it can be used to derive new insights across a variety of biological disciplines.

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Vitamin D-binding protein: multifunctional component of blood serum

Annals of the Russian academy of medical sciences ◽

10.15690/vramn1396 ◽

2021 ◽

Vol 76 (1) ◽

pp. 103-110

Author(s):

Alexandra A. Povaliaeva ◽

Ekaterina A. Pigarova ◽

Anastasia A. Romanova ◽

Larisa K. Dzeranova ◽

Artem Y. Zhukov ◽

...

Keyword(s):

Vitamin D ◽

Binding Sites ◽

Binding Protein ◽

Vitamin D Metabolites ◽

Biological Functions ◽

Vitamin D Binding Protein ◽

Fatty Acid Binding ◽

Physiological Properties ◽

Steroid Binding ◽

Tumor Pathogenesis

Vitamin D-binding protein (DBP) was discovered more than half a century ago as a polymorphic serum protein and is currently characterized by a variety of physiological properties. First of all, DBP carries the bulk of vitamin D metabolites circulating in the bloodstream, while albumin is the second most important transport protein, especially in patients with a low concentration of DBP in serum. Since it was discovered that only 12% of the total circulating DBP have occupied steroid binding sites, a vigorous study of other potential biological roles of DBP was initiated: actin utilization, regulation of inflammation and innate immunity mechanisms, fatty acid binding, effects on bone metabolism and participation in the tumor pathogenesis. This review focuses on the main known biological functions of DBP.

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Cockayne Syndrome B protein selectively interacts and resolves intermolecular DNA G-quadruplex structures

10.1101/2021.03.25.436565 ◽

2021 ◽

Author(s):

Denise Liano ◽

Marco Di Antonio

Keyword(s):

Ribosomal Dna ◽

Living Cells ◽

Cockayne Syndrome ◽

Biological Functions ◽

Loss Of Function ◽

Endogenous Protein ◽

G Quadruplex ◽

Dna Strands ◽

Low Probability ◽

Dna Strand

AbstractGuanine-rich DNA can fold into secondary structures known as G-quadruplexes (G4s). G4s can form from a single DNA-strand (intramolecular) or from multiple DNA-strands (intermolecular), but studies on their biological functions have been often limited to intramolecular G4s, owing to the low probability of intermolecular G4s to form within genomic DNA. Herein, we report that the endogenous protein Cockayne Syndrome B (CSB) binds with picomolar affinity to intermolecular G4s, whilst displaying negligible binding towards intramolecular structures. We also observed that CSB can selectively resolve intermolecular G4s in an ATP independent fashion. Our study demonstrates that intermolecular G4s formed within ribosomal DNA are natural substrates for CSB, strongly suggesting that these structures might be formed in the nucleolus of living cells. Given that CSB loss of function elicits premature ageing phenotypes, our findings indicate that the interaction between CSB and ribosomal DNA intermolecular G4s is essential to maintain cellular homeostasis.

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CircRHOT1 Mediated Cell Proliferation, Apoptosis and Invasion of Pancreatic Cancer Cells by Sponging miR-125a-3p

10.21203/rs.3.rs-19451/v1 ◽

2020 ◽

Author(s):

Sunkai Ling ◽

Yanru He ◽

Xiaoxue Li ◽

Mingyue Hu ◽

Yu Ma ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Biological Function ◽

Diagnostic Marker ◽

Biological Functions ◽

Normal Tissues ◽

Qrt Pcr ◽

Pancreatic Cancer Cells ◽

Cancer Tissues

Abstract Background: The present study aimed to investigate the mechanistic biological function of circRHOT1 in pancreatic cancer cells.Methods: The expression of circRHOT1 and miR-125a-3p in pancreatic cancer tissues and their paired adjacent normal tissues was quantified by qRT-PCR. By knocking down or overexpressing circRHOT1 and miR-125a-3p in pancreatic cancer cells, their functions and potential mechanisms were explored.Results: circRHOT1 was overexpressed in pancreatic cancer tissues and cell lines, and it was found to directly bind to miR-125a-3p, acting as an endogenous sponge to inhibit its activity. Knockdown of circRHOT1 expression significantly inhibited proliferation as well as invasion, and it promoted apoptosis of pancreatic cancer cells via the regulation of E2F3 through the targeting of miR-125a-3p.Conclusion: Taken together, our results demonstrated that circRHOT1 plays critical roles in regulating the biological functions of pancreatic cancer cells, suggesting that circRHOT1 may serve as a potential diagnostic marker and therapeutic target for patients with pancreatic cancer.

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Normas naturales y funciones biológicas

Contrastes Revista Internacional de Filosofía ◽

10.24310/contrastescontrastes.v0i0.1162 ◽

2013 ◽

Author(s):

Cristian Saborido

Keyword(s):

Biological Function ◽

Biological Systems ◽

Philosophy Of Biology ◽

Current Debate ◽

Biological Functions ◽

Naturalistic Account ◽

Organizational Approach

RESUMENEn este trabajo abordo el problema de la fundamentación teórica de la noción de normatividad natural desde una perspectiva naturalista. Presento el debate actual sobre las funciones biológicas en filosofía de la biología, en el cual pueden encontrarse algunos intentos de fundamentar las normas naturales a través del concepto de función biológica. Sostengo que el enfoque predominante etiológico-evolutivo no es capaz justificar la adscripción de normas naturales en los sistemas biológicos y propongo que la nueva perspectiva organizacional está en la mejor posición para ofrecer un tratamiento naturalista de la teleología biológica y de la normatividad natural.PALABRAS CLAVENORMATIVIDAD, FUNCIÓN, NATURALISMO, TELEOLOGÍA, MALFUNCIÓN, ORGANIZACIÓNABSTRACTIn this paper I consider the problem of the theoretical grounding of the notion of natural normativity for the naturalistic perspective. I present the current debate on biological functions in philosophy of biology in which there are some attempts to ground natural norms through the notion of biological function. I argue that the mainstream account, i.e. the evolutive-etiological approach, is not able to ground the ascription of natural norms in biological systems and I defend that the new organizational approach is in the best position to offer an adequate naturalistic account for biological teleology and natural normativity.KEYWORDSNORMATIVITY, FUNCTION, NATURALISM, TELEOLOGYGY, MALFUNCTION, ORGANIZATION

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Biomimetic Drug Delivery Systems Oriented by Biological Function in Tumor Targeting

Current Drug Targets ◽

10.2174/1389450122666210114095859 ◽

2021 ◽

Vol 22 ◽

Author(s):

Rui Wang ◽

Xianyi Sha

Keyword(s):

Drug Delivery ◽

Tumor Targeting ◽

Drug Delivery Systems ◽

Biological Function ◽

Delivery Systems ◽

Biological Functions ◽

Simple Preparation ◽

Targeting Delivery ◽

Clinical Transformation ◽

Endogenous Substances

: The emergence of nanoscale drug delivery systems provides new opportunities for targeting delivery of chemotherapeutic drugs and has achieved excellent results. In recent years, with the arising of the concept of intelligent drug delivery systems, the design and preparation of carriers have become more and more complicated, which is not conducive to clinical transformation. Researchers are gradually focusing on biomimetic nanoscale drug delivery systems, trying to combine the physicochemical properties of nanoscale carriers with the natural biological functions of endogenous substances, so as to boost tumor targeting delivery. In this article, we first classify and introduce biomimetic nanoscale drug delivery systems, and then emphasize their unique biological functions. The biomimetic nanoscale drug delivery systems have the advantages of simple preparation, powerful functions, and low immunogenicity, having a good application prospect.

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LncTarD: a manually-curated database of experimentally-supported functional lncRNA–target regulations in human diseases

Nucleic Acids Research ◽

10.1093/nar/gkz985 ◽

2019 ◽

Cited By ~ 4

Author(s):

Hongying Zhao ◽

Jian Shi ◽

Yunpeng Zhang ◽

Aimin Xie ◽

Lei Yu ◽

...

Keyword(s):

Molecular Mechanisms ◽

Sequence Data ◽

Human Diseases ◽

Regulatory Mechanisms ◽

Biological Functions ◽

Functional Dynamics ◽

Disease Associations ◽

Non Coding Rnas ◽

User Friendly ◽

Pan Cancer

Abstract Long non-coding RNAs (lncRNAs) are associated with human diseases. Although lncRNA–disease associations have received significant attention, no online repository is available to collect lncRNA-mediated regulatory mechanisms, key downstream targets, and important biological functions driven by disease-related lncRNAs in human diseases. We thus developed LncTarD (http://biocc.hrbmu.edu.cn/LncTarD/ or http://bio-bigdata.hrbmu.edu.cn/LncTarD), a manually-curated database that provides a comprehensive resource of key lncRNA–target regulations, lncRNA-influenced functions, and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD offers (i) 2822 key lncRNA–target regulations involving 475 lncRNAs and 1039 targets associated with 177 human diseases; (ii) 1613 experimentally-supported functional regulations and 1209 expression associations in human diseases; (iii) important biological functions driven by disease-related lncRNAs in human diseases; (iv) lncRNA–target regulations responsible for drug resistance or sensitivity in human diseases and (v) lncRNA microarray, lncRNA sequence data and transcriptome data of an 11 373 pan-cancer patient cohort from TCGA to help characterize the functional dynamics of these lncRNA–target regulations. LncTarD also provides a user-friendly interface to conveniently browse, search, and download data. LncTarD will be a useful resource platform for the further understanding of functions and molecular mechanisms of lncRNA deregulation in human disease, which will help to identify novel and sensitive biomarkers and therapeutic targets.

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ZDOG: zooming in on dominating genes with mutations in cancer pathways

BMC Bioinformatics ◽

10.1186/s12859-019-3326-z ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Rudi Alberts ◽

Jinyu Chen ◽

Louxin Zhang

Keyword(s):

Somatic Mutations ◽

Positional Information ◽

Signalling Pathways ◽

Biological Functions ◽

Tree Model ◽

Master Regulators ◽

Cancer Pathways ◽

Link Type ◽

Dominating Tree ◽

User Friendly

Abstract Background Inference of cancer-causing genes and their biological functions are crucial but challenging due to the heterogeneity of somatic mutations. The heterogeneity of somatic mutations reveals that only a handful of oncogenes mutate frequently and a number of cancer-causing genes mutate rarely. Results We develop a Cytoscape app, named ZDOG, for visualization of the extent to which mutated genes may affect cancer pathways using the dominating tree model. The dominator tree model allows us to examine conveniently the positional importance of a gene in cancer signalling pathways. This tool facilitates the identification of mutated “master” regulators even with low mutation frequency in deregulated signalling pathways. Conclusions We have presented a model for facilitating the examination of the extent to which mutation in a gene may affect downstream components in a signalling pathway through its positional information. The model is implemented in a user-friendly Cytoscape app which will be freely available upon publication. Availability Together with a user manual, the ZDOG app is freely available at GitHub (https://github.com/rudi2013/ZDOG). It is also available in the Cytoscape app store (http://apps.cytoscape.org/apps/ZDOG) and users can easily install it using the Cytoscape App Manager.

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LncExpDB: an expression database of human long non-coding RNAs

Nucleic Acids Research ◽

10.1093/nar/gkaa850 ◽

2020 ◽

Vol 49 (D1) ◽

pp. D962-D968 ◽

Cited By ~ 2

Author(s):

Zhao Li ◽

Lin Liu ◽

Shuai Jiang ◽

Qianpeng Li ◽

Changrui Feng ◽

...

Keyword(s):

Expression Profiles ◽

Biological Functions ◽

Protein Coding ◽

Web Interfaces ◽

Functional Studies ◽

Protein Coding Genes ◽

Genes Expression ◽

Wide Range ◽

Non Coding Rnas ◽

User Friendly

Abstract Expression profiles of long non-coding RNAs (lncRNAs) across diverse biological conditions provide significant insights into their biological functions, interacting targets as well as transcriptional reliability. However, there lacks a comprehensive resource that systematically characterizes the expression landscape of human lncRNAs by integrating their expression profiles across a wide range of biological conditions. Here, we present LncExpDB (https://bigd.big.ac.cn/lncexpdb), an expression database of human lncRNAs that is devoted to providing comprehensive expression profiles of lncRNA genes, exploring their expression features and capacities, identifying featured genes with potentially important functions, and building interactions with protein-coding genes across various biological contexts/conditions. Based on comprehensive integration and stringent curation, LncExpDB currently houses expression profiles of 101 293 high-quality human lncRNA genes derived from 1977 samples of 337 biological conditions across nine biological contexts. Consequently, LncExpDB estimates lncRNA genes’ expression reliability and capacities, identifies 25 191 featured genes, and further obtains 28 443 865 lncRNA-mRNA interactions. Moreover, user-friendly web interfaces enable interactive visualization of expression profiles across various conditions and easy exploration of featured lncRNAs and their interacting partners in specific contexts. Collectively, LncExpDB features comprehensive integration and curation of lncRNA expression profiles and thus will serve as a fundamental resource for functional studies on human lncRNAs.

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Characterization of the Putative Replisome Organizer of the Lactococcal Bacteriophage r1t

Journal of Virology ◽

10.1128/jvi.76.20.10234-10244.2002 ◽

2002 ◽

Vol 76 (20) ◽

pp. 10234-10244 ◽

Cited By ~ 10

Author(s):

Manuel Zúñiga ◽

Blandine Franke-Fayard ◽

Gerard Venema ◽

Jan Kok ◽

Arjen Nauta

Keyword(s):

Dna Replication ◽

Binding Sites ◽

Direct Repeats ◽

Dnase I Footprinting ◽

Phage Dna ◽

Cognate Gene ◽

Phage Spp1 ◽

Dna Strand ◽

Protection Pattern

ABSTRACT Analysis of the nucleotide sequence of the genome of the lactococcal bacteriophage r1t showed that it may encode at least two proteins involved in DNA replication. On the basis of its similarity with the G38P protein encoded by the Bacillus subtilis phage SPP1, the product of orf11 (Pro11) is thought to be involved in the initiation of phage DNA replication. This protein was overexpressed in Lactococcus lactis and partially purified. Gel retardation analysis using various r1t DNA fragments indicates that Pro11 specifically binds to a sequence located within its cognate gene. DNase I footprinting showed that Pro11 protects a stretch of DNA of 47 bp. This region spans four 6-bp short direct repeats, which suggests that the region contains four binding sites for Pro11. 1,10-Phenanthroline-copper footprinting confirmed the protection of the hexamers. An asymmetric protection pattern of each strand was observed, suggesting that Pro11 contacts each DNA strand separately at contiguous hexamers. We propose a model for the binding of Pro11 to its target sites that may account for the torsion strain required for strand opening at the origin of replication.

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Analysis of Array-CGH Data Using the R and Bioconductor Software Suite

Comparative and Functional Genomics ◽

10.1155/2009/201325 ◽

2009 ◽

Vol 2009 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Winfried A. Hofmann ◽

Anja Weigmann ◽

Marcel Tauscher ◽

Britta Skawran ◽

Tim Focken ◽

...

Keyword(s):

Array Cgh ◽

Molecular Genetic ◽

Comparative Genomic ◽

Accurate Identification ◽

Genome Wide ◽

Versatile Tool ◽

Breakpoint Detection ◽

Dna Copy Number Alterations ◽

User Friendly

Background. Array-based comparative genomic hybridization (array-CGH) is an emerging high-resolution and high-throughput molecular genetic technique that allows genome-wide screening for chromosome alterations. DNA copy number alterations (CNAs) are a hallmark of somatic mutations in tumor genomes and congenital abnormalities that lead to diseases such as mental retardation. However, accurate identification of amplified or deleted regions requires a sequence of different computational analysis steps of the microarray data.Results. We have developed a user-friendly and versatile tool for the normalization, visualization, breakpoint detection, and comparative analysis of array-CGH data which allows the accurate and sensitive detection of CNAs.Conclusion. The implemented option for the determination of minimal altered regions (MARs) from a series of tumor samples is a step forward in the identification of new tumor suppressor genes or oncogenes.

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