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Gene Regulatory Networks (gene + regulatory_network)
Selected AbstractsCross talking of network motifs in gene regulation that generates temporal pulses and spatial stripesGENES TO CELLS, Issue 11 2005Shuji Ishihara Gene regulatory networks contain several substructures called network motifs, which frequently exist throughout the networks. One of such motifs found in Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster is the feed-forward loop, in which an effector regulates its target by a direct regulatory interaction and an indirect interaction mediated by another gene product. Here, we theoretically analyze the behavior of networks that contain feed-forward loops cross talking to each other. In response to levels of the effecter, such networks can generate multiple rise-and-fall temporal expression profiles and spatial stripes, which are typically observed in developmental processes. The mechanism to generate these responses reveals the way of inferring the regulatory pathways from experimental results. Our database study of gene regulatory networks indicates that most feed-forward loops actually cross talk. We discuss how the feed-forward loops and their cross talks can play important roles in morphogenesis. [source] Transcriptional control of Rohon-Beard sensory neuron development at the neural plate borderDEVELOPMENTAL DYNAMICS, Issue 4 2009Christy Cortez Rossi Abstract Rohon-Beard (RB) mechanosensory neurons are among the first sensory neurons to develop, and the process by which they adopt their fate is not completely understood. RBs form at the neural plate border (NPB), the junction between neural and epidermal ectoderm, and require the transcription factor prdm1a. Here, we show that prior to RB differentiation, prdm1a overlaps extensively with the epidermal marker dlx3b but shows little overlap with the neuroectodermal markers sox3 and sox19a. Birthdating analysis reveals that the majority of RBs are born during gastrulation in zebrafish, suggesting that it is during this period that RBs become specified. Expression analysis in prdm1a and neurogenin1 mutant and dlx3b/dlx4b morpholino-injected embryos suggests that prdm1a is upstream of dlx3b, dlx4b, and neurogenin1 at the NPB. mRNA for neurogenin1 or dlx3b/dlx4b can rescue the lack of RBs in prdm1a mutants. Based on these data, we suggest a preliminary gene regulatory network for RB development. Developmental Dynamics 238:931,943, 2009. © 2009 Wiley-Liss, Inc. [source] Adaptive modeling and discovery in bioinformatics: The evolving connectionist approachINTERNATIONAL JOURNAL OF INTELLIGENT SYSTEMS, Issue 5 2008Nikola Kasabov Most biological processes that are currently being researched in bioinformatics are complex, dynamic processes that are difficult to model and understand. The paper presents evolving connectionist systems (ECOS) as a general approach to adaptive modeling and knowledge discovery in bioinformatics. This approach extends the traditional machine learning approaches with various adaptive learning and rule extraction procedures. ECOS belong to the class of incremental local learning and knowledge-based neural networks. They are applied here to challenging problems in Bioinformatics, such as: microarray gene expression profiling, gene regulatory network (GRN) modeling, computational neurogenetic modeling. The ECOS models have several advantages when compared to the traditional techniques: fast learning, incremental adaptation to new data, facilitating knowledge discovery through fuzzy rules. © 2008 Wiley Periodicals, Inc. [source] Discovering functions and revealing mechanisms at molecular level from biological networksPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 16 2007Shihua Zhang Abstract With the increasingly accumulated data from high-throughput technologies, study on biomolecular networks has become one of key focuses in systems biology and bioinformatics. In particular, various types of molecular networks (e.g., protein,protein interaction (PPI) network; gene regulatory network (GRN); metabolic network (MN); gene coexpression network (GCEN)) have been extensively investigated, and those studies demonstrate great potentials to discover basic functions and to reveal essential mechanisms for various biological phenomena, by understanding biological systems not at individual component level but at a system-wide level. Recent studies on networks have created very prolific researches on many aspects of living organisms. In this paper, we aim to review the recent developments on topics related to molecular networks in a comprehensive manner, with the special emphasis on the computational aspect. The contents of the survey cover global topological properties and local structural characteristics, network motifs, network comparison and query, detection of functional modules and network motifs, function prediction from network analysis, inferring molecular networks from biological data as well as representative databases and software tools. [source] MicroRNAs as Immune Regulators: Implications for TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010A. Harris The explosion of genetic information from recent advances in sequencing technologies, bioinformatics and genomics highlights the importance of understanding mechanisms involved in gene expression and regulation. Over the last decade, it has become clear that small ribonucleic acids (RNAs) are a central component of the cellular gene regulatory network. MicroRNAs (miRNAs) are a family of endogenous, small, noncoding single-stranded RNA of ,22 nucleotides in length that act as posttranscriptional gene regulatory elements. MicroRNAs can inhibit de novo protein synthesis by blocking translation through base-pairing with complementary messenger RNA (mRNA) and also suppress translation by promoting degradation of target mRNA. MicroRNAs are intimately involved in a variety of biologic processes including development, hematopoietic cell differentiation, apoptosis and proliferation. To date, over 800 human miRNAs have been identified, though the biologic function of only a fraction of miRNAs has been elucidated. Here, we discuss how miRNAs are produced, identified and quantitated, and focus on several key miRNAs that govern expression of genes relevant to allograft rejection, tolerance induction and posttransplant infection. Finally, we discuss potential ways in which the miRNA network can be modulated that ultimately may offer new strategies to promote long-term graft survival. [source] Statistical Reconstruction of Transcription Factor Activity Using Michaelis,Menten KineticsBIOMETRICS, Issue 3 2007R. Khanin Summary The basic building block of a gene regulatory network consists of a gene encoding a transcription factor (TF) and the gene(s) it regulates. Considerable efforts have been directed recently at devising experiments and algorithms to determine TFs and their corresponding target genes using gene expression and other types of data. The underlying problem is that the expression of a gene coding for the TF provides only limited information about the activity of the TF, which can also be controlled posttranscriptionally. In the absence of a reliable technology to routinely measure the activity of regulators, it is of great importance to understand whether this activity can be inferred from gene expression data. We here develop a statistical framework to reconstruct the activity of a TF from gene expression data of the target genes in its regulatory module. The novelty of our approach is that we embed the deterministic Michaelis,Menten model of gene regulation in this statistical framework. The kinetic parameters of the gene regulation model are inferred together with the profile of the TF regulator. We also obtain a goodness-of-fit test to verify the fit of the model. The model is applied to a time series involving the Streptomyces coelicolor bacterium. We focus on the transcriptional activator cdaR, which is partly responsible for the production of a particular type of antibiotic. The aim is to reconstruct the activity profile of this regulator. Our approach can be extended to include more complex regulatory relationships, such as multiple regulatory factors, competition, and cooperativity. [source] "Natural restoration" can generate biological complexityCOMPLEXITY, Issue 2 2005Emile ZuckerkandlArticle first published online: 16 DEC 200 Abstract Factor complexes engaged in transcriptional regulation of gene expression and their cognate DNA elements recurrently suffer mutational damage that can result in deadaptations in the mutual fit of interacting macromolecules. Such mutations can spread in populations by drift if their functional consequences are not severe. Mutational restorations of the damaged complexes may ensue and can take many forms. One of these forms would represent spontaneous increases in gene interaction complexity and correlated aspects of organismic complexity. In this particular mode of restoration, restabilization of a factor/factor/DNA complex occurs through the binding of an additional factor. Factors added under such circumstances to regulatory kits of individual genes are thought to be at the origin of a slow but persistent "complexity drive." This drive seems to be resisted in many forms whose developmental outcome has reached a finish line difficult to pass, but imposes itself along other lines of phylogenetic descent. In the process of restoration by an additional factor, the chances are significant that the original regulatory control of a target gene is not recovered exactly and that the restored gene expression has novel spatial, temporal, or quantitative characteristics. These new characteristics, which represent a functional transfer of the gene to a new domain of activity, may be selectable, even when the physicochemical properties of the gene product have remained largely unchanged. As a consequence of such activity transfers under quasi-constancy of the molecular properties of the protein encoded by the regulation's target gene, the activity domain originally covered by that target gene may be left at least in part functionally vacant. At that point, an unmodified duplicate of the target gene and of its original regulatory dependencies probably becomes in turn selectable. A causal link is therefore predicted between the regulatory specialization and selection of one of two duplicates and the regulatory maintenance and selection of the other. A conserved increase in gene number would result indirectly from the regulatory shift in paralogs, and the organism's complexity would be increased in this sense also, complexity as number of genes in addition to complexity as number of regulatory factors per gene. It is thus proposed that increased biological complexity, innovation in the gene regulatory network, and the development of a novel evolutionary potential can be the result, counterintuitively, of conservative forces that intervene when mutations play a survivable form of havoc with the system of gene regulation. Increasing complexity, then, could be seen as one of the side effects of "natural restoration." This phrase designates the mutational re-establishment in the gene whose regulation has been damaged of a functionally effective activity pattern, albeit, perhaps, with changes in its mode of expression in regard to location, time, and rate. The higher complexity, innovation in the gene regulatory network, of higher organisms,their very character of higher organisms,would to a significant extent be a side effect of episodes of natural selection aimed at functional restoration, not at complexity itself. Regulatory impairment, the point of departure of the process outlined, represents a controller gene disease. It thus may well be the case that molecular diseases, the effects on the individual of inheritable structural decay, are among the conditions of the evolution of higher organisms. © 2005 Wiley Periodicals, Inc. Complexity 11: 14,27, 2005 [source] Ontogeny of vasotocin-expressing cells in zebrafish: Selective requirement for the transcriptional regulators orthopedia and single-minded 1 in the preoptic areaDEVELOPMENTAL DYNAMICS, Issue 4 2008Jennifer L. Eaton Abstract The neurohypophysial peptide arginine vasotocin, and its mammalian ortholog arginine vasopressin, influence a wide range of physiological and behavioral responses, including aspects of sexual and social behaviors, osmoregulation, stress response, metabolism, blood pressure, and circadian rhythms. Here, we demonstrate that, in zebrafish (Danio rerio), the vasotocin precursor gene arginine vasotocin-neurophysin (avt) is expressed in two domains in the developing embryo: the dorsal preoptic area and the ventral hypothalamus. In the dorsal preoptic area, avt -expressing cells are intermingled with isotocin-neurophysin (ist) -expressing cells, and these neurons project to the neurohypophysis (posterior pituitary). In the dorsal preoptic area, the transcriptional regulators orthopedia b (otpb) and simple-minded 1 (sim1) are required for expression of both avt and ist. In contrast, otp and sim1 are not required for avt expression in the ventral hypothalamus. Thus, the development of these two avt expression domains is influenced by separate gene regulatory networks. Developmental Dynamics 237:995,1005, 2008. © 2008 Wiley-Liss, Inc. [source] Abundant genetic variation in transcript level during early Drosophila developmentEVOLUTION AND DEVELOPMENT, Issue 6 2008Sergey V. Nuzhdin SUMMARY Variation in gene expression may underlie many important evolutionary traits. However, it is not known at what stage in organismal development changes in gene expression are most likely to result in changes in phenotype. One widely held belief is that changes in early development are more likely to result in changes in downstream phenotypes. In order to discover how much genetic variation for transcript level is present in natural populations, we studied zygotic gene expression in nine inbred lines of Drosophila melanogaster at two time points in their development. We find abundant variation for transcript level both between lines and over time; close to half of all expressed genes show a significant line effect at either time point. We examine the contribution of maternally loaded genes to this variation, as well as the contribution of variation in upstream genes to variation in their downstream targets in two well-studied gene regulatory networks. Finally, we estimate the dimensionality of gene expression in these two networks and find that,despite large numbers of varying genes,there appear to be only two factors controlling this variation. [source] Cross talking of network motifs in gene regulation that generates temporal pulses and spatial stripesGENES TO CELLS, Issue 11 2005Shuji Ishihara Gene regulatory networks contain several substructures called network motifs, which frequently exist throughout the networks. One of such motifs found in Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster is the feed-forward loop, in which an effector regulates its target by a direct regulatory interaction and an indirect interaction mediated by another gene product. Here, we theoretically analyze the behavior of networks that contain feed-forward loops cross talking to each other. In response to levels of the effecter, such networks can generate multiple rise-and-fall temporal expression profiles and spatial stripes, which are typically observed in developmental processes. The mechanism to generate these responses reveals the way of inferring the regulatory pathways from experimental results. Our database study of gene regulatory networks indicates that most feed-forward loops actually cross talk. We discuss how the feed-forward loops and their cross talks can play important roles in morphogenesis. [source] Transcription profile in mouse four-cell, morula, and blastocyst: Genes implicated in compaction and blastocoel formationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2007Xiang-Shun Cui Abstract To gain insight into early embryo development, we utilized microarray technology to compare gene expression profiles in four-cell (4C), morula (MO), and blastocyst (BL) stage embryos. Differences in spot intensities were normalized, and grouped by using Avadis Prophetic software platform (version 3.3, Strand Genomics Ltd.) and categories were based on the PANTHER and gene ontology (GO) classification system. This technique identified 622 of 7,927 genes as being more highly expressed in MO when compared to 4C (P,<,0.05); similarly, we identified 654 of 9,299 genes as being more highly expressed in BL than in MO (P,<,0.05). Upregulation of genes for cytoskeletal, cell adhesion, and cell junction proteins were identified in the MO as compared to the 4C stage embryos, this means they could be involved in the cell compaction necessary for the development to the MO. Genes thought to be involved in ion channels, membrane traffic, transfer/carrier proteins, and lipid metabolism were also identified as being expressed at a higher level in the BL stage embryos than in the MO. Real-time RT-PCR was performed to confirm differential expression of selected genes. The identification of the genes being expressed in here will provide insight into the complex gene regulatory networks effecting compaction and blastocoel formation. Mol. Reprod. Dev. © 2006 Wiley-Liss, Inc. [source] Diversification and co-option of RAD-like genes in the evolution of floral asymmetryTHE PLANT JOURNAL, Issue 1 2007Catherine E. L. Baxter Summary To understand how changes in gene regulatory networks lead to novel morphologies, we have analysed the evolution of a key target gene, RAD, controlling floral asymmetry. In Antirrhinum, flower asymmetry depends on activation of RAD in dorsal regions of the floral meristem by the upstream regulators CYC and DICH. We show that Arabidopsis, a species with radially symmetric flowers, contains six RAD -like genes, reflecting at least three duplications since the divergence of Antirrhinum and Arabidopsis. Unlike the situation in Antirrhinum, none of the Arabidopsis RAD -like genes are activated in dorsal regions of the flower meristem. Rather, the RAD -like genes are expressed in distinctive domains along radial or ab-adaxial axes, consistent with a range of developmental roles. Introduction of a RAD genomic clone from Antirrhinum into Arabidopsis leads to a novel expression pattern that is distinct from the expression pattern of RAD in Antirrhinum and from the endogenous RAD -like genes of Arabidopsis. Nevertheless, RAD is able to influence developmental targets in Arabidopsis, as ectopic expression of RAD has developmental effects in this species. Taken together, our results suggest that duplication and divergence of RAD -like genes has involved a range of cis- and trans- regulatory changes. It is possible that such changes led to the coupling of RAD to CYC regulation in the Antirrhinum lineage and hence the co-option of RAD had a role in the generation of flower dorsoventral asymmetry. [source] Gene networks and liar paradoxesBIOESSAYS, Issue 10 2009Mark Isalan Abstract Network motifs are small patterns of connections, found over-represented in gene regulatory networks. An example is the negative feedback loop (e.g. factor A represses itself). This opposes its own state so that when ,on' it tends towards ,off' , and vice versa. Here, we argue that such self-opposition, if considered dimensionlessly, is analogous to the liar paradox: ,This statement is false'. When ,true' it implies ,false' , and vice versa. Such logical constructs have provided philosophical consternation for over 2000,years. Extending the analogy, other network topologies give strikingly varying outputs over different dimensions. For example, the motif ,A activates B and A. B inhibits A' can give switches or oscillators with time only, or can lead to Turing-type patterns with both space and time (spots, stripes or waves). It is argued here that the dimensionless form reduces to a variant of ,The following statement is true. The preceding statement is false'. Thus, merely having a static topological description of a gene network can lead to a liar paradox. Network diagrams are only snapshots of dynamic biological processes and apparent paradoxes can reveal important biological mechanisms that are far from paradoxical when considered explicitly in time and space. [source] The interplay between transcription factors and microRNAs in genome-scale regulatory networksBIOESSAYS, Issue 4 2009Natalia J. Martinez Abstract Metazoan genomes contain thousands of protein-coding and non-coding RNA genes, most of which are differentially expressed, i.e., at different locations, at different times during development, or in response to environmental signals. Differential gene expression is achieved through complex regulatory networks that are controlled in part by two types of trans -regulators: transcription factors (TFs) and microRNAs (miRNAs). TFs bind to cis -regulatory DNA elements that are often located in or near their target genes, while miRNAs hybridize to cis -regulatory RNA elements mostly located in the 3, untranslated region of their target mRNAs. Here, we describe how these trans -regulators interact with each other in the context of gene regulatory networks to coordinate gene expression at the genome-scale level, and discuss future challenges of integrating these networks with other types of functional networks. [source] The evolving role of microRNAs in animal gene expressionBIOESSAYS, Issue 5 2006Katlin B. Massirer MicroRNAs (miRNAs) constitute an abundant family of 22-nucleotide RNAs that base-pair to target mRNAs and typically inhibit their expression. To assess the global impact of animal miRNAs on gene regulation, the expression of predicted targets and their cognate miRNAs was extensively analyzed in mammals and Drosophila.1,2 In general, targets are co-expressed at relatively low or undetectable levels in the same tissues as the miRNAs predicted to regulate them. Additionally, genes that are highly co-expressed with miRNAs usually lack target sites. The authors conclude that many animal genes are under evolutionary pressure to maintain or avoid complementary sites to miRNAs.1,2 Thus, the miRNA pathway broadly contributes to the complex gene regulatory networks that shape animal tissue development and identity. BioEssays 28: 449,452, 2006. © 2006 Wiley Periodicals, Inc. [source] | |||||||||||||