• The allosteric interactions and regulation of molecular chaperones and protein kinases allow for molecular communication and event coupling in signal transduction networks. (utoronto.ca)
  • Biophysical modeling of allosteric regulation in the protein kinases has offered additional insights into organizing principles of kinase activation by molecular chaperones that may be orchestrated by a cross-talk between key regulatory regions. (utoronto.ca)
  • The results of biophysical and computational systems biology analyses combined with proteomics experiments have been integrated into a graph-based network model of allosteric regulation. (utoronto.ca)
  • Network-defined modularity of interacting components and cross-talk in signal transduction networks are quantified through molecular mechanism of allosteric regulation. (utoronto.ca)
  • Absolute Quantification of Transcription Factors Reveals Principles of Gene Regulation in Erythropoiesis. (ox.ac.uk)
  • These analyses provide a unique quantitative framework to understand transcriptional regulation of cell differentiation in a dynamic context. (ox.ac.uk)
  • Furthermore, differential geometry analyses reveal mechanisms driving early megakaryocyte appearance and elucidate asymmetrical regulation within the PU.1-GATA1 circuit. (amillionpieces.com)
  • PageMan analysis revealed several significantly enriched categories altered by MeJA+NaCl treatment, compared with NaCl treatment alone, including genes involved in secondary metabolism, glutathione-based redox regulation, cell cycle, transcription factors (TFs), and other signal transductions (such as calcium and ROS). (frontiersin.org)
  • In this study, we present a computational framework to identify miRNA-disease associations, and further construct a bipartite miRNA-disease network for systematically analyzing the global properties of miRNA regulation of disease genes. (biomedcentral.com)
  • MicroRNAs (MiRNAs) are important regulators that can strongly affect cellular functions including proliferation, differentiation, and apoptosis through post-transcriptional negative regulation of target gene expression [ 1 ]. (biomedcentral.com)
  • A better comprehension of cellular hierarchies, epigenetic effects, clonal evolution, and their impact on gene regulation might help to understand disease progression, stratify patient risk, and help to improve the treatment of hematopoietic malignancies in the future. (uni-heidelberg.de)
  • In the last two decades, our understanding of human gene regulation has improved tremendously. (uni-frankfurt.de)
  • Non-coding regions are known to regulate gene expression, and the finding indicates that alterations in regulation networks play a larger role in disease risk than protein-coding variants. (jax.org)
  • The team used massively parallel reporter assays (MPRA) to assess the effects of variants on gene expression in cultured MIN6 mouse β cells, which have been found to accurately model the regulation networks found in human islet cells. (jax.org)
  • In addition to classical gene regulatory networks noted above, we have recently identified a central role for additional biologic mechanisms, namely gene regulation by chromatin regulators and by noncoding RNAs. (stanford.edu)
  • They also showed that cross-regulation between col and eya in muscle progenitor cells is required for specification of muscle identity, revealing a new parallel between the myogenic regulatory networks operating in Drosophila and vertebrates. (sdbonline.org)
  • Although microRNAs (miRNAs) are physically small, they have been shown to play an important role in gene regulation [ 1 ]. (hindawi.com)
  • The application of the systems biology approach to the analysis of a gene regulatory network is demonstrated with a case study of the regulation of p21 by multiple miRNAs [ 4 ]. (hindawi.com)
  • The network combining putative targets of TF and miRNA regulation with experimentally proven molecular interactions was constructed and visualized. (hindawi.com)
  • The arrangement of methyl chemical groups on the cytosine base in DNA (known as "cytosine methylation"), which specifies when genes are to be turned on or off, are one form of epigenomic regulation that may highly influence disease and health in the brain. (neurosciencenews.com)
  • The GO and KEGG analyses carried out on the cis target gene of lncRNAs showed that the lncRNAs play an important role in the regulation of flowering spinach. (biomedcentral.com)
  • This study is the first report on identifying bolting and flowering-related lncRNAs based on transcriptome sequencing in spinach, which provides a useful resource for future functional genomics studies, genes expression researches, evaluating genes regulatory networks and molecular breeding programs in the regulation of the genetic mechanisms related to bolting in spinach. (biomedcentral.com)
  • Our loss- and gain-of-function studies, as well as the observed genetic interactions among Dorsocross, tinman and pannier , suggest that co-expression of these three genes in the cardiac mesoderm, which also involves cross-regulation, plays a major role in the specification of cardiac progenitors. (biologists.com)
  • A rapid overview of this morphologic scheme provides the framework for further studying the processes and regulation involved in development. (medscape.com)
  • Stem cell homeostasis is maintained through epigenetic mechanisms that are highly dynamic in regulating the chromatin structure as well as specific gene transcription programs. (wikipedia.org)
  • The synergistic roles of the Hsp90-Cdc37 chaperone machinery and protein kinases in biology and disease have stimulated extensive structural and functional studies of regulatory mechanisms underlying the Hsp90-kinase interactions. (utoronto.ca)
  • Allosteric interactions of the Hsp90 with cochaperones and protein kinase clients can determine regulatory mechanisms and cellular functions of many signaling proteins and cascades. (utoronto.ca)
  • By showcasing a family of cyclin-dependent (CDK) kinases that display a broad repertoire of chaperone dependencies, we discovered that unique functional dynamics signatures and chaperone addiction of CDK4 and CDK7 client proteins can explain divergences in their regulatory mechanisms that require a confluence of events, including formation of the inhibitory ternary complex, substrate recruitment and activation loop phosphorylation. (utoronto.ca)
  • This illustrates how our GRN can be used to better understand potential mechanisms of drug resistance acquisition.Graphical abstract captionA network model of the MLL-AF4 regulatory landscape identifies feed-forward loop and cascade motifs. (ox.ac.uk)
  • Doug Kellogg's lab is working to elucidate these mechanisms, using biochemistry, genetics, and mathematical modeling to understand signaling networks that are required for control of cell size and cell growth. (ucsc.edu)
  • We also observed that most diseases in the same co-regulated module tended to belong to the same disease category, indicating that these diseases might share similar miRNA regulatory mechanisms. (biomedcentral.com)
  • Analyses of gene regulatory networks (GRNs) provide the ability to understand the underlying genetic and developmental mechanisms responsible for the origin of morphological structures both in the development of an individual and across entire evolutionary lineages. (echinobase.org)
  • A model based which contains the Oct4/Sox2/Nanog core as well its interaction upon regulatory mechanisms inferred from ChIP-on-chip and with a few other key genes. (lu.se)
  • Epigenetic control of gene expression lasts through multiple cell divisions without alterations in primary DNA sequence and can occur via mechanisms that include histone modification and DNA methylation. (stanford.edu)
  • Noncoding RNA sequences can regulate gene expression via interactions with epigenetic and other control mechanisms. (stanford.edu)
  • Currently, an increasing number of studies are being carried out to deepen our understanding of miRNA regulatory mechanisms and functions. (hindawi.com)
  • Studies in several vertebrate models and Drosophila have uncovered a surprising degree of evolutionary conservation of regulatory mechanisms and genes that control early cardiogenesis. (biologists.com)
  • Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. (elifesciences.org)
  • Chromosomal translocations of the Mixed Lineage Leukemia gene (MLL) produce MLL fusion proteins such as MLL-AF4, causing poor prognosis acute lymphoblastic leukemias (ALLs). (ox.ac.uk)
  • Chemically induced gene expression changes were characterized by qRT-PCR, global run-on sequencing (GRO-seq) and immunoblotting, and the network of cooperative proteins of GATA4 and NKX2-5 were further explored by the examination of the GATA4 and NKX2-5 interactome by BioID. (biomedcentral.com)
  • Gene Ontology analysis revealed a strong enrichment in proteins with DNA binding and/or transcription-regulatory properties. (sdbonline.org)
  • a map is constructed that shows interactions among molecular entities (such as genes, proteins and RNAs), using information from literature and databases. (hindawi.com)
  • We have developed a powerful computational framework for revealing the genetic basis of bacterial traits by correlating the inheritance patterns of genes and phenotypes across all the sequenced bacterial genomes (Jim et al. (columbia.edu)
  • We developed a computational framework to identify miRNA-disease associations by performing random walk analysis, and focused on the functional link between miRNA targets and disease genes in protein-protein interaction (PPI) networks. (biomedcentral.com)
  • Dr. Tan has developed a general computational framework for identifying noncoding mutations that confer disease risk. (chop.edu)
  • ABSTRACTRegulatory interactions mediated by transcription factors (TFs) make up complex networks that control cellular behavior. (ox.ac.uk)
  • This GRN identified several key transcription factors, including RUNX1, that regulate target genes using feed-forward loop and cascade motifs. (ox.ac.uk)
  • My lab previously identified several transcription factors (homeobox genes and T-box genes) involved in formation and patterning of both the primary embryonic axis and the limb axis in vertebrates. (nih.gov)
  • We are analyzing the normal developmental function of early transcription factors that regulate digit patterning (Gli3, 5'Hoxd), with the long-term aim of linking regulatory cascades and patterned gene expression to the morphogenesis of specific structures. (nih.gov)
  • Additionally, scATAC-seq allows to map the binding of transcription factors (TF) and infer cell-specific regulatory networks. (uni-heidelberg.de)
  • Background: Recent studies have associated the transcription factors, Oct4, Sox2 and Nanog as parts of a self-regulating network which is responsible for maintaining embryonic stem cell properties: self renewal and pluripotency. (lu.se)
  • Recent findings on the control of gene expression programs has had an essential impact on our perception of transcriptional misregulation in pathologic conditions, as many different disorders are due to mutations in regulatory sequences and their cognate transcription factors. (tigem.it)
  • Indeed, numerous mendelian diseases are attributable to alterations in transcription factors acting at the node of gene regulatory networks, often responsible for subtle changes at critical moments of cell fate decisions. (tigem.it)
  • In all these organisms, cardiac induction in the lateral mesoderm involves the concerted action of signals mediated by Bmp, Wnt and Fgf family members, which act upon cardiogenic genes encoding NK homeodomain, Gata and T-box transcription factors (reviewed by Zaffran and Frasch, 2002 ). (biologists.com)
  • Fully understanding these gene regulatory networks (GRNs) offers greater insight into the consequences of disease-causing perturbations than studying single TF binding events in isolation. (ox.ac.uk)
  • The evolution of high throughput technologies that measure gene expression levels has created a data base for inferring GRNs (a process also known as reverse engineering of GRNs). (biomedcentral.com)
  • This paper concentrates on quantitative modelling of gene regulatory networks (GRNs) using DNA microarray data, as this is more informative than qualitative analysis of biological data. (biomedcentral.com)
  • In the first part of my talk, I will introduce an analytical framework dynamo ( https://github.com/aristoteleo/dynamo-release ), and highlight dynamo's power to overcome fundamental limitations of conventional splicing-based RNA velocity analyses to enable accurate velocity estimations on a metabolically labeled human hematopoiesis scRNA-seq dataset. (amillionpieces.com)
  • In this respect, he is using a broad range of methods including immunohistochemical analyses, histological staining procedures and ultrastructural investigations as well as gene expression analyses and phylogenomic approaches. (uni-goettingen.de)
  • The catalog of driver genes involved in the development of several malignancies has grown in recent years, as a result of whole-exome and whole-genome analyses of cohorts of tumors, mainly within the framework of large international consortia [ 3 , 4 ]. (biomedcentral.com)
  • Gene expression at these histones regulated by epigenetic modifications is critical in restricting the embryonic stem cell to desired cell lineages and developing cellular memory. (wikipedia.org)
  • The recent expansion of repeated HERV sequences has offered a framework for genetic and epigenetic innovation. (mdpi.com)
  • Treatment with the IDH1 inhibitor revealed a partially reversible pattern of accessibility while other mutation-induced epigenetic modifications could not be reverted. (uni-heidelberg.de)
  • Further, we developed a Random Forests classifier to predict gene expression using genic (gene length, intron frequency, etc.) and epigenetic features. (uni-frankfurt.de)
  • Upon evaluating different feature sets, we found that genic features are as predictive, of gene expression, as the epigenetic features. (uni-frankfurt.de)
  • Fig. 4: ASAP-seq and CITE-seq reveal coordinated and distinct changes in chromatin, RNA and protein levels. (nature.com)
  • Examples include biological networks such as phylogenetic network, gene regulatory network, metabolic pathways and protein‐protein interaction networks. (cmcrc.com)
  • We report the results of integrative systems biology studies of the Hsp90 chaperone and protein kinases with an atomic level analysis of the communication pathways regulating conformational equilibrium of theses protein systems in signaling networks. (utoronto.ca)
  • Among our primary findings is the emerging evidence that a small number of functional motifs may be utilized by the chaperone and protein kinases to act collectively as central regulators of the intermolecular communications, ATP hydrolysis, and protein client binding in signaling networks. (utoronto.ca)
  • Network modelling and percolation analysis approaches were used to emulate thermal unfolding and characterize conformational landscapes of a wide range of protein kinases, revealing that chaperone dependency of protein kinase clients may be linked with the elevated conformational mobility of their inactive states induced by dynamic and energetic polarization of kinase lobes. (utoronto.ca)
  • Based on these findings, we developed a computational synthetic biology framework for design and re-engineering signal transduction networks and pathways that involve cross-talk between molecular chaperones and protein kinase clients. (utoronto.ca)
  • The increasingly growing fraction of cancer driver mutations emerging from sequencing studies of protein kinase genes appeared to be inactivating or kinase-dead leading to the loss of function. (utoronto.ca)
  • Our study offers a systems-based perspective on drug design and re-engineering of signaling networks by unravelling relationships between protein kinase networks with molecular chaperones and binding specificity of targeted kinase drugs. (utoronto.ca)
  • Furthermore, we establish the first gene regulatory network of cell fate commitment that integrates temporal protein stoichiometry data with mRNA measurements. (ox.ac.uk)
  • The transcriptomic and epigenomic regulatory landscape of the MAC genome, which has 80% protein-coding genes and short intergenic regions, is poorly understood. (uni-frankfurt.de)
  • It regulates Sp7 protein expression and induces expression of major bone matrix protein genes, such as Col1a1, Spp1, Ibsp, Bglap2, and Fn1 ( 7 , 8 ). (frontiersin.org)
  • High density arrays of extraordinarily sensitive integrated microring resonators will allow many gene and protein signatures to be simultaneously quantitated from a single patient sample. (nih.gov)
  • ncRNAs with more than 200 nucleotides are considered as lncRNAs, which originate from intronic and exonic regions of protein-coding genes in both sense and antisense strands, as well as from the intergenic regions [ 21 ]. (biomedcentral.com)
  • Imposed upon this gross morphological description is the modern understanding of gene expression and protein elucidation, which bring about these developmental processes. (medscape.com)
  • RiboNucleic Acids (RNAs) are ubiquitous macromolecules within biological systems, capable of performing a wide range of regulatory and catalytic functions. (dagstuhl.de)
  • Further, using RAPID, we investigated the aberrations of endo-siRNAs, and their respective transcriptomic alterations caused by an RNAi pathway triggered by feeding small RNAs against a target gene. (uni-frankfurt.de)
  • Although some key flowering responsive genes have been identified in spinach, non-coding RNA molecules like long non-coding RNAs (lncRNAs) were not investigated yet. (biomedcentral.com)
  • MicroRNAs (miRNAs) are well-recognized for their abilities to regulate gene expression post-transcriptionally in plants and animals. (frontiersin.org)
  • 报告主题简介 :Single-cell RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. (amillionpieces.com)
  • Identifying the direct target promoters of developmental gene-regulators will be critical to understand how these regulators function and to link regulatory cascades in developmental genetic programs to the basic cellular processes that drive morphogenesis of anatomic structures. (nih.gov)
  • Thus, understanding how normal transcription programs are regulated during development may also help to decipher abnormal gene expression patterns in tumors and devise new strategies to intercept cellular targets driving tumor cell behavior. (nih.gov)
  • His efforts are focused on the identification of the complete set of biomineralizing effector genes in the pulmonate gastropod Lymnaea stagnalis , and on identifying the gene regulatory and cellular communication events that coordinate the initiation of shell formation in the early snail embryo. (uni-goettingen.de)
  • The lab uses marine model systems including the starfish, Patiria miniata and the jellyfish, Clytia hemisphaerica that are exceptionally suited for high-resolution livecell microscopy assays, which are frequently combined in his lab with quantitative image analysis and biophysical modeling to reveal conserved principles of cellular organization. (uni-goettingen.de)
  • One step in this direction is thus to understand exactly which downstream genes and cellular processes become affected in the outcome of driver alterations. (biomedcentral.com)
  • Due to cellular heterogeneity in the heart, the activation of gene programs representing specific atrial and ventricular cardiomyocyte subtypes would be highly desirable. (biomedcentral.com)
  • Initial analysis of Collier/Early B Cell Factor function in the lymph gland revealed the role of the Posterior Signaling Center (PSC) in mounting a dedicated cellular immune response to wasp parasitism. (sdbonline.org)
  • Our studies have revealed how constitutively activating and kinase-dead mutations could play context-dependent opposing roles in cancer and may be simultaneously present in a variety of oncogenic kinases that are regulated by their interactions with the Hsp90 chaperone. (utoronto.ca)
  • Her lab focuses on mutations that cause changes in gene expression by affecting a process called alternative splicing of RNA. (ucsc.edu)
  • One in eight women in the United States will develop breast cancer in her lifetime, yet only about 15 percent of these cancers have been linked to inherited gene mutations. (ucsc.edu)
  • Mouse genetics have spotlighted many mutations affecting this process, and a wealth of embryologic information from experimental manipulations in chick has uncovered a network of inductive tissue interactions, providing a rich conceptual framework for molecular analysis. (nih.gov)
  • Phylogenetic analysis of gene expression. (echinobase.org)
  • My research focuses on the study of macroevolutionary patterns of taxononomic diversity, morphological disparity and biogeographic distribution in a phylogenetic framework. (uni-goettingen.de)
  • Visualisation is an effective analysis tool for complex networks. (cmcrc.com)
  • Our framework is based on the tight integration of analysis, visualisation and interaction methods. (cmcrc.com)
  • 100.000 cCREs in total), dispersed within the genome and present in cis-regulatory regions of ~81% of human genes, as calculated following gene enrichment analysis. (mdpi.com)
  • Furthermore, we have developed a genome-wide epistasis analysis framework that efficiently reveals the organization of these genes within signaling and regulatory networks such as the Rcs phosphorelay pathway and the cyclic-di-GMP second-messenger system. (columbia.edu)
  • METHODS: We evaluated the relationship between clinical features and OTX2-AS1 expression, prognostic factors, and the significant involvement of OTX2-AS1 in function using various statistical methods, such as Kaplan-Meier method, Cox regression analysis, Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis. (bvsalud.org)
  • Subsequent transcriptomic analysis identified genes differentially regulated by MeJA+NaCl treatment and NaCl alone. (frontiersin.org)
  • Further weighted gene co-expression network analysis (WGCNA) uncovered that turquoise and yellow gene modules were tightly linked to antioxidant enzymes activity and ion content, respectively. (frontiersin.org)
  • At the moment, several methods of discovering qualitative causal relationships between genes with high accuracy from microarray data exist, but large scale quantitative analysis on real biological datasets cannot be performed, to date, as existing approaches are not suitable for real microarray data which are noisy and insufficient. (biomedcentral.com)
  • This paper performs an analysis of several existing evolutionary algorithms for quantitative gene regulatory network modelling. (biomedcentral.com)
  • Both inference and analysis of this kind of model are difficult tasks, thus global, (high-level), analysis of the network, has its attractions. (biomedcentral.com)
  • Furthermore, a bipartite miRNA-disease network was constructed, from which several miRNA-disease co-regulated modules were identified by hierarchical clustering analysis. (biomedcentral.com)
  • In addition, random walk analysis is a global network distance measurement that is usually used to measure similarities between the nodes of a network, and previous reports have demonstrated its effectiveness in candidate disease gene prioritization [ 9 , 10 ]. (biomedcentral.com)
  • Furthermore, I used the experimental and data analysis framework to analyze specific molecular features of the three AML subgroups. (uni-heidelberg.de)
  • Our analysis revealed subsets of genes, whose expression is positively associated with H3K27me3, different to the otherwise reported negative association with gene expression in many other organisms. (uni-frankfurt.de)
  • There are two main reasons why the catalogs of cancer drivers produced by the aforementioned projects and others need to be broken down into related sets of genes for deeper analysis. (biomedcentral.com)
  • More detailed structure-function analysis revealed a distinct subclass of GATA4/NKX2-5 inhibitory compounds with an acetyl lysine-like domain that contributed to ventricular cells (%Myl2-eGFP+). (biomedcentral.com)
  • This paper deals with the analysis of the dynamics of chemical reaction networks, developing a theoretical framework based only on graphical knowledge and applying regardless of the particular form of kinetics. (sontaglab.org)
  • Network analysis pinpointed several well-known flowering-related genes such as ELF , COL1 , FLT , and FPF1 and also some putative TFs like MYB, WRKY, GATA, and MADS-box that are important regulators of flowering in spinach and could be potential targets for lncRNAs. (biomedcentral.com)
  • However, the comparative transcriptome analysis of two spinach accessions with different bolting times identified genome-wide gene expression profiling and large-scale discovery of flowering-related genes from vegetative and reproductive leaves [ 13 ]. (biomedcentral.com)
  • Including 4 multidrug-resistant tuberculosis isolates from Australia citizens epidemiologically linked to the TSPZ into the transmission network analysis revealed 2 probable cross-border transmission events. (cdc.gov)
  • There is now an urgent need for methods that rapidly and comprehensively reveal the genetic basis of phenotypes across the microbial biosphere. (columbia.edu)
  • By applying this framework to mild resistance, we have identified a large number of loci whose genetic perturbations significantly affect antibiotic sensitivity. (columbia.edu)
  • Limb development is a particularly attractive model for unraveling the function and interaction of such regulatory components, because it is very accessible to study and is extremely well conserved between genetic (mouse) and embryologic (chick) model organisms and humans. (nih.gov)
  • Altered islet cell CRE activity has been implicated in T2D genetic risk, but previous investigations have found altered gene expression levels or transcription accessibility at only about a quarter of the T2D-associated locations under steady-state conditions. (jax.org)
  • The model dynamics both suggests the microarray data can quantify functionality of the genetic network. (lu.se)
  • This allows us to derive the stationary distributions of a large class of BRNs, including autophosphorylation networks of EGFR, PAK1, and Aurora B kinase and a genetic toggle switch. (sontaglab.org)
  • For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs), and 62,305 trans-eQTL, with the majority showing cell type specific effects on gene expression. (iscb.org)
  • The model revealed quantitative imbalances in TFs' cross-antagonistic relationships that underlie lineage determination. (ox.ac.uk)
  • In my second section of my talk, I will talk about Spateo, a general framework for quantitative spatiotemporal modeling of single-cell resolution spatial transcriptomics. (amillionpieces.com)
  • The application of systems biology principles to developmental biology promises to reveal the quantitative interrelationships between signaling and regulatory systems necessary to support robust physiological processes, and thereby provide a framework for the interpretation of the pathology (especially cancer) resulting from gross or subtle disturbances in these interrelationships. (nih.gov)
  • Reporter gene assays were conducted to examine combinatorial effects of GATA-targeted compounds and bromodomain and extraterminal domain (BET) inhibition on chamber-specific gene expression. (biomedcentral.com)
  • In this line, reporter gene assays with combinatorial treatment of 3i-1000 and the BET bromodomain inhibitor (+)-JQ1 demonstrated the cooperative role of GATA4 and BRD4 in the modulation of chamber-specific cardiac gene expression. (biomedcentral.com)
  • The miRNA-mRNA interactions were verified by dual-luciferase reporter gene assays and experiments using mimics miRNA or their inhibitors. (frontiersin.org)
  • Dual-luciferase reporter gene assays demonstrated Arhgap11a as the target of miR-211-5p. (frontiersin.org)
  • Spateo delivers novel methods for digitizing spatial layers/columns to identify spatially-polar genes, and develops a comprehensive framework of cell-cell interaction to reveal spatial effects of niche factors and cell type-specific ligand-receptor interactions. (amillionpieces.com)
  • coarse-grained and fine-grained models, where the former contain less detail on interactions between genes. (biomedcentral.com)
  • 6 ] assessed potential miRNA-disease interactions through a miRNA-miRNA functional similarity network that was constructed based on the similarity of miRNA-associated diseases. (biomedcentral.com)
  • Developmental processes such as axis formation and organogenesis employ regulatory components and interactions that are often also used in normal tissue renewal/homeostasis in the adult organism, as well as contributing to the pathogenesis of disease when aberrantly reactivated. (nih.gov)
  • We first construct a p21 regulatory network based on data from the literature and further expand it using algorithms that predict molecular interactions. (hindawi.com)
  • In addition, we will have regular interactions with the permanent staff at Physical Chemistry and will get to meet students in their fi nal studies thereby enlarging our network and creating possibilities for future recruitment. (lu.se)
  • Lastly, Spateo introduces the concept of 'morphometric vector field' of cell migrations, and integrates spatial differential geometry to unveil regulatory programs underlying various organogenesis patterns of Drosophila. (amillionpieces.com)
  • Her lab has recently worked with gene expression patterns during sexual reproduction and regeneration of syllids. (uni-goettingen.de)
  • Multiple miRNA-mRNA prediction databases were searched by differentially expressed genes (DEGs) to obtain pairs of a miRNA-DEG regulatory network. (frontiersin.org)
  • In his post-doc at Whitehead Institute with Dr. Jonathan Weissman, Xiaojie developed Dynamo (aristoteleo/dynamo-release) to infers absolute RNA velocity with metabolic labeling enabled single-cell RNA-seq, reconstructs continuous vector fields that predict fates of individual cells, employs differential geometry to extract underlying gene regulatory network regulations, and ultimately predicts optimal reprogramming paths and makes nontrivial in silico perturbation predictions. (amillionpieces.com)
  • Of interest, we have observed in a rodent transgenerational model of intrauterine growth restriction (IUGR) that a diet supplemented with essential nutrients, yet unaltered in its caloric content, prevents adult metabolic disease and is associated with abrogation of reprogrammed gene expression. (nih.gov)
  • Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics. (elifesciences.org)
  • However, the chance to successfully develop patient-tailored therapies is still very limited because reprogramming technologies lack a comprehensive understanding of the molecular processes involved, and manufacturing cells requires knowledge of the exact combination of genes governing the transitions from the starting cell type to the target type. (tigem.it)
  • Using a novel iterative framework developed in a companion manuscript, we have analyzed single-cell RNA-seq data obtained from mouse embryonic stem cells taken at various time points during early germ layer differentiation to identify cell types as well as the lineage relationships between these individual cell types. (harvard.edu)
  • This allowed us to essentially map out a lineage tree in gene expression space that describes the continuous gene expression dynamics of early germ layer differentiation. (harvard.edu)
  • Our findings reveal that cell types found during early in vitro germ layer differentiation are discrete both transcriptionally as well as functionally. (harvard.edu)
  • Recently, we have focused on the role of Shh/Gli3 and 5'Hoxd genes in regulating several aspects of limb development, including early digit patterning, as well as condensation and differentiation of cartilage precursors during final morphogenesis of the limb skeleton. (nih.gov)
  • Also, under/over-expression studies of the master regulator Oct4 have revealed that some self-renewal/pluripotency as well as differentiation genes are expressed in a biphasic manner with respect to the concentration of Oct4. (lu.se)
  • The model also predicts that reprogramming the network from a differentiated state, in particular the endoderm state, into a stem cell state, is best achieved by over-expressing Nanog, rather than by suppression of differentiation genes such as Gata-6. (lu.se)
  • TFs being expressed and the downstream differentiation target been established as candidates to regulate both pluripotency and genes being shut off [11]. (lu.se)
  • The ontogeny of hematopoietic stem cells (HSCs) and T-cell differentiation are driven by a series of gene expression programs over time. (chop.edu)
  • This process is mediated by 2 mutually exclusive programs of gene expression: 1) an undifferentiated program supporting proliferation by stem cells within the basal layer and 2) a differentiation program instructing growth arrest and differentiation-associated programmed cell death in suprabasal layers. (stanford.edu)
  • We are currently pursuing studies of the dominant signaling and gene regulatory networks that control this process, including the Ras/MAPK cascade, which is required for stem cell-mediated self-renewal and the p53 transcription factor family member, p63, which is required for epidermal differentiation. (stanford.edu)
  • Recently, miRNA-messenger RNA (mRNA) regulatory relationships have been confirmed during biological processes, including osteogenic differentiation. (frontiersin.org)
  • An MC3T3-E1-based microarray dataset (accessioned as GSE46400) downloaded from the Gene Expression Omnibus included MC3T3-E1 cells with or without 14-day osteoblast differentiation osteoblast induction. (frontiersin.org)
  • The Arhgap11a, H2afx, Chek2, Dlgap5, and Chek1 were hub genes downregulated in MC3T3-E1 cells after osteogenic differentiation, verified by RT-qPCR results. (frontiersin.org)
  • The integration of this new information with previous findings has allowed us to draw a more complete pathway of regulatory events during cardiac induction and differentiation in Drosophila . (biologists.com)
  • DNA Microarray technology enables us to measure mRNA concentrations in a cell for a large number of genes at the same time. (biomedcentral.com)
  • Herein, we used bioinformatic approaches to analyze the transcriptome datasets from two different accessions Viroflay and Kashan at two vegetative and reproductive stages to reveal novel lncRNAs and the construction of the lncRNA-mRNA co-expression network. (biomedcentral.com)
  • MLL-AF4 is thought to drive leukemogenesis by directly binding to genes and inducing aberrant overexpression of key gene targets, including anti-apoptotic factors such as BCL-2. (ox.ac.uk)
  • MiRNA mainly performs its regulatory function through its targets, and thus we presumed that if targets of a miRNA correlate with disease genes then the miRNA tends to be associated with the disease. (biomedcentral.com)
  • Functional connections between miRNA targets and disease genes could be obtained via PPI network. (biomedcentral.com)
  • A major goal of our research program is the identification of the direct transcriptional targets of these factors to unravel the regulatory networks controlling limb development. (nih.gov)
  • So how can scientists wade through the puzzle of variable environments and behaviors combined with complex genetics to reveal the biology underlying T2D and identify targets for more effective treatments? (jax.org)
  • Furthermore, I am able to identify other driver genes that cause tumorigenesis through the alteration of very similar sets of targets. (biomedcentral.com)
  • Good visualisation reveals the hidden structure of the networks and amplifies human understanding, thus leading to new insights, new findings, new hypothesis and predictions. (cmcrc.com)
  • Sites associated with insulin transcription and secretion were prominent among those with decreased activity, and the findings reveal the specific regulatory elements that respond to ER stress conditions. (jax.org)
  • Methodology/Principal Findings: We construct a dynamical model of a minimalistic network, extracted from ChIP-on-chip and microarray data as well as literature studies. (lu.se)
  • We suggest that future studies need to distinguish transcriptomic changes caused by RNAi inducing techniques and actual regulatory changes. (uni-frankfurt.de)
  • He is also developing computational algorithms for constructing models of transcriptional regulatory and signaling networks by integrating multi-dimensional genomic, epigenomic, and transcriptomic datasets. (chop.edu)
  • Additionally, as a member of the NCI-funded Human Tumor Atlas Network, his research team has established the Center for Pediatric Tumor Cell Atlas to better understand clonal evolution and tumor heterogeneity at single-cell level for three types of high-risk pediatric cancers. (chop.edu)
  • Daniel Kim's lab studies the role of long noncoding RNA molecules (lncRNAs) in gene expression and cancer. (ucsc.edu)
  • Exploiting the aforementioned catalogs of driver genes, for example, we recently revealed the mutational landscape of chromatin regulatory factors (CRFs) in cancer [ 5 ]. (biomedcentral.com)
  • MicroRNAs (miRNAs) are potent effectors in gene regulatory networks where aberrant miRNA expression can contribute to human diseases such as cancer. (hindawi.com)
  • Even though the environment is known to play health practice requires advanced, networked, ronmental cancer cluster investigations and an important role in human health, no com- computer-assisted technology to process a assessments (Fiore et al. (cdc.gov)
  • First, we briefly present the ana- include both the delivery of health- municable diseases (NCDs) includ- lytical framework used in this chap- care services and broader individu- ing cancer (UN, 2015). (who.int)
  • PA A and regulatory environment, including national cancer policies, to cancer prevention and control? (who.int)
  • Recent work on the regulatory genomic basis of development in cidaroid echinoids, sand dollars, heart urchins, and other nonmodel echinoderms provides an ideal dataset with which to explore GRN evolution in a comparative framework. (echinobase.org)
  • A genomic regulatory network for development. (echinobase.org)
  • Dr. Tan is developing cutting-edge genomic and computational tools to profile and model the gene regulatory circuitry in these two developmental systems. (chop.edu)
  • We present DISTILLER, a data integration framework for the inference of transcriptional module networks. (nih.gov)
  • I could demonstrate that leukemic cells could be successfully distinguished from the microenvironment based on marker gene annotation from the human cell atlas and ploidy inference. (uni-heidelberg.de)
  • The core gene regulatory network controlling these transitions consists of a system made up of coupled SNAIL/miRNA-34 and ZEB1/miRNA-200 subsystems. (sontaglab.org)
  • This has opened up the possibility to carry out systematic studies to uncover the repertoire of functionally related groups of driver genes. (biomedcentral.com)
  • The past decade has been characterized by unprecedented progress in the field of descriptive genomics, increasing the capacity to finely map regulatory regions and DNA sequence variants, which are responsible for the phenotypic differences between individuals as well as disease susceptibility. (tigem.it)
  • J21] Kim M, Zorraquino V, Tagkopoulos I. Microbial forensics: predicting phenotypic characteristics and environmental conditions from large-scale gene expression profiles. (ucdavis.edu)
  • Surprisingly, the level of regulatory complexity seemed lower than that which would be expected from RegulonDB, indicating that complex regulatory programs tend to decrease the degree of modularity. (nih.gov)
  • Developmental systems also afford an excellent avenue to study complex regulatory circuits designed to ensure the robust functioning of a normal process. (nih.gov)
  • In the current report, a systematic approach is implemented to catalogue regulatory elements within HERVs, as a roadmap to potential functions of HERV sequences in gene networks. (mdpi.com)
  • I analyzed the presence of HERV sequences on consensus cis-regulatory elements (cCREs) from ENCODE data. (mdpi.com)
  • His studies have revealed a repertoire of highly dynamic transcriptional regulatory sequences as well as transcriptional regulators that are previously uncharacterized. (chop.edu)
  • Additional studies are underway to experimentally test novel regulatory DNA sequences and transcriptional regulators. (chop.edu)
  • The hypergeometric distribution method considers the number of overlapping genes while neglecting the functional link between them, and the scoring system used in their study only considered the direct neighbour information of each miRNA in the miRNA functional network. (biomedcentral.com)
  • K-mer Set Memory (KSM) motif representation enables accurate prediction of the impact of regulatory variants. (stanford.edu)
  • A Bayesian framework for estimating cell type composition from DNA methylation without the need for methylation reference. (stanford.edu)
  • To understand the dynamics of bacterial growth physiology and size control in dynamic nutrient environments, we have developed a coarse-grained proteome sector model which connects gene expression to growth rate and division control, and accurately predicts the cell-level E. coli response to nutrient perturbations in both exponential and stationary phase seen in experimental data 5 , 25 . (nature.com)
  • Finally, in silico perturbations predict cell-fate diversions induced by gene perturbations. (amillionpieces.com)
  • It provides a framework to explore strategies of reprogramming a cell from a differentiated state to a stem cell state through directed perturbations. (lu.se)
  • We employed a chromatin state segmentation approach, on nucleosomes and histone marks, which revealed genes with active, repressive, and bivalent chromatin states. (uni-frankfurt.de)
  • 2017), Paleogenomics of echinoids reveals an ancient o. (echinobase.org)
  • She was a member of two principal committees of the Australian National Health and Medical Research Council, the Australian Health Ethics Committee and the Embryo Research Licensing Committee in the triennium from 2015 to 2018 and the Gene Technology Ethics and Community Consultative Committee of the Office of the Gene Technology Regulator from 2017 to 2018. (nhmrc.gov.au)
  • By systematically analyzing the global properties of the miRNA-disease network, we found that only a small number of miRNAs regulated genes involved in various diseases, genes associated with neurological diseases were preferentially regulated by miRNAs and some immunological diseases were associated with several specific miRNAs. (biomedcentral.com)
  • Ongoing studies find more parallels between the complex apoptosis regulatory networks of vertebrates with locusts and beetles, but not with dipteran flies. (uni-goettingen.de)
  • Such an approach is characterized by an iterative process, including biological data acquisition and integration, network construction, mathematical modeling and experimental validation. (hindawi.com)
  • To investigate a gene regulatory network, an iterative process of four steps is needed. (hindawi.com)
  • Importantly, our results show that cell types occupy discrete locations in gene expression space and correspondingly, cells exhibit abrupt changes in gene expression profile as they transition from one cell type to another. (harvard.edu)
  • Besides comparing gene- and cell-level quality control summaries in both one- and two-dimensional settings, we further quantified these at the batch- and cluster-level. (biomedcentral.com)
  • Recent advances in single-cell genomics provide an alternative to largely gene-centric metagenomics studies, enabling whole-genome sequencing of uncultivated bacteria. (hse.ru)
  • To directly test this model of Shh function, we have restored cell survival in Shh mutant embryos after transient Shh expression by concomitant removal of the pro-apoptotic genes Bak/Bax to intercept cell death, in order to rescue the proposed late Shh role. (nih.gov)
  • Cell type prediction revealed extensive malignant cell diversity and a phenotype skewed towards stem- and progenitor-like populations in MLL-EDC4 leukemic cells. (uni-heidelberg.de)
  • At the core of the network reside Oct4, Sox2 and Nanog, into embryonic stem cells [1,2,3,4,5], have made major inroads which form a self-organized core of the TFs maintaining into stem cell biology. (lu.se)
  • A computational model of master regulators that are required for successful reprogramming the dynamics of this core network has revealed that it functions as of a differentiated cell into a cell exhibiting stem cell like a bistable switch, which in the on state, corresponds to all these properties. (lu.se)
  • Pharmacological modulation of cell fate decisions and developmental gene regulatory networks holds promise for the treatment of heart failure. (biomedcentral.com)
  • Collectively, these results indicate the potential for therapeutic alteration of cell fate decisions and pathological gene regulatory networks by GATA4-targeted compounds modulating chamber-specific transcriptional programs in multipotent cardiac progenitor cells and cardiomyocytes. (biomedcentral.com)
  • Together, this study shows that the PSC is dispensable for blood cell progenitor maintenance and reveals the key role of the conserved transcription factor Col as an intrinsic regulator of hematopoietic progenitor fate. (sdbonline.org)
  • The researchers, collaborating as part of the National Institute of Health's BRAIN Initiative Cell Census Network (BICCN), report the new data today in a special issue of the journal Nature . (neurosciencenews.com)
  • A Bayesian active learning experimental design for inferring signaling networks. (stanford.edu)
  • We trained a Bayesian machine learning neural network model to generate a neuroimaging phenotype and AD score representing the probability of AD using structural MRI data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Cohort (cut-off 0.5, AUC 0.92, PPV 0.90, NPV 0.93). (cdc.gov)
  • Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics. (echinobase.org)
  • Conclusions: The computational model provides a mechanistic understanding of how different lineages arise from the dynamics of the underlying regulatory network. (lu.se)
  • In previous work, we have developed an approach to understanding the long-term dynamics of classes of chemical reaction networks, based on rate-dependent Lyapunov functions. (sontaglab.org)
  • This reveals the unique properties of their stochastic dynamics such as robustness, sensitivity, and multimodality. (sontaglab.org)
  • We hypothesized that a high fat diet in non-human primates would induce changes in hepatic chromatin structure resulting in altered expression of fetal genes critical to the development of childhood and adult obesity. (nih.gov)
  • These models allowed us to make and experimentally test predictions as to how cells respond to various signals and gene expression changes. (harvard.edu)
  • Taking advantage of the finding that certain locations in gene expression space are more "stable" (i.e., far more cells are found in these locations than expected by chance) than others, we used a novel framework to build a probabilistic model of the underlying gene regulatory network. (harvard.edu)
  • However, this model minimizes the potential for circuit generated regulatory outputs, including gene repression. (ox.ac.uk)
  • To better understand the MLL-AF4 driven regulatory landscape, we integrated ChIP-seq, patient RNA-seq and CRISPR essentiality screens to generate a model GRN. (ox.ac.uk)
  • In order to model a GRN, genes are viewed as variables that change their (expression) values in time. (biomedcentral.com)
  • Using the limb as a model for vertebrate organogenesis, we deleted Shh at different developmental times in genetically engineered mice with a conditional, floxed-Shh gene and inducible Cre to determine the temporal requirements for Shh during limb development. (nih.gov)
  • To these ends his team is also developing methods to characterize gene function in this nontraditional model organism. (uni-goettingen.de)
  • For a better understanding of the regulatory role of miRNAs in coordinating gene expression, we here present a systems biology approach combining data-driven modeling and model-driven experiments. (hindawi.com)
  • Based on the network structure, a detailed mechanistic model is established and its parameter values are determined using data. (hindawi.com)
  • The systems biology approach, combining data-driven modeling and model-driven experiments, provides a systematic and comprehensive perspective on the regulatory roles of miRNAs in gene regulatory networks [ 3 - 5 ]. (hindawi.com)
  • Next, the network was translated into a detailed mechanistic model, which was characterized and validated with experimental data. (hindawi.com)
  • In addition we will address important areas of modern epidemiology such as the influence of early life factors on adult health and disease, but also the importance of the gene-diet-microbiota interaction for body function and health. (lu.se)
  • We then interventions within the health sector analytical framework (Atun et al. (who.int)