Search results for "Regulatory Networks"
showing 10 items of 107 documents
Network reconstruction for trans acting genetic loci using multi-omics data and prior information.
2022
Background: Molecular measurements of the genome, the transcriptome, and the epigenome, often termed multi-omics data, provide an in-depth view on biological systems and their integration is crucial for gaining insights in complex regulatory processes. These data can be used to explain disease related genetic variants by linking them to intermediate molecular traits (quantitative trait loci, QTL). Molecular networks regulating cellular processes leave footprints in QTL results as so-called trans-QTL hotspots. Reconstructing these networks is a complex endeavor and use of biological prior information can improve network inference. However, previous efforts were limited in the types of priors…
Inferring slowly-changing dynamic gene-regulatory networks
2015
Dynamic gene-regulatory networks are complex since the interaction patterns between their components mean that it is impossible to study parts of the network in separation. This holistic character of gene-regulatory networks poses a real challenge to any type of modelling. Graphical models are a class of models that connect the network with a conditional independence relationships between random variables. By interpreting these random variables as gene activities and the conditional independence relationships as functional non-relatedness, graphical models have been used to describe gene-regulatory networks. Whereas the literature has been focused on static networks, most time-course experi…
Hub-Centered Gene Network Reconstruction Using Automatic Relevance Determination
2012
Network inference deals with the reconstruction of biological networks from experimental data. A variety of different reverse engineering techniques are available; they differ in the underlying assumptions and mathematical models used. One common problem for all approaches stems from the complexity of the task, due to the combinatorial explosion of different network topologies for increasing network size. To handle this problem, constraints are frequently used, for example on the node degree, number of edges, or constraints on regulation functions between network components. We propose to exploit topological considerations in the inference of gene regulatory networks. Such systems are often…
Pathway network inference from gene expression data
2014
[EN] Background: The development of high-throughput omics technologies enabled genome-wide measurements of the activity of cellular elements and provides the analytical resources for the progress of the Systems Biology discipline. Analysis and interpretation of gene expression data has evolved from the gene to the pathway and interaction level, i.e. from the detection of differentially expressed genes, to the establishment of gene interaction networks and the identification of enriched functional categories. Still, the understanding of biological systems requires a further level of analysis that addresses the characterization of the interaction between functional modules. Results: We presen…
Early asymmetric cues triggering the dorsal/ventral gene regulatory network of the sea urchin embryo
2014
Dorsal/ventral (DV) patterning of the sea urchin embryo relies on a ventrally-localized organizer expressing Nodal, a pivotal regulator of the DV gene regulatory network. However, the inceptive mechanisms imposing the symmetry-breaking are incompletely understood. In Paracentrotus lividus, the Hbox12 homeodomain-containing repressor is expressed by prospective dorsal cells, spatially facing and preceding the onset of nodal transcription. We report that Hbox12 misexpression provokes DV abnormalities, attenuating nodal and nodal-dependent transcription. Reciprocally, impairing hbox12 function disrupts DV polarity by allowing ectopic expression of nodal. Clonal loss-of-function, inflicted by b…
Defining the genomic signature of totipotency and pluripotency during early human development.
2013
The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs), still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs) from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation netw…
Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature
2015
Despite massive investments in drug research and development, the significant decline in the number of new drugs approved or translated to clinical use raises the question, whether single targeted drug discovery is the right approach. To combat complex systemic diseases that harbour robust biological networks such as cancer, single target intervention is proved to be ineffective. In such cases, network pharmacology approaches are highly useful, because they differ from conventional drug discovery by addressing the ability of drugs to target numerous proteins or networks involved in a disease. Pleiotropic natural products are one of the promising strategies due to their multi-targeting and d…
Gene Regulation and Species-Specific Evolution of Free Flight Odor Tracking in Drosophila
2018
Running title: flight evolution in Drosophila This is an invited contribution to the special issue on Genetics of Adaptation based on a symposium of the same name at the National Centre for Biological Sciences (TIFR, Bangalore, India) in November 2016; International audience; The flying ability of insects has coevolved with the development of organs necessary to take-off from the ground, generate, and modulate lift during flight in complex environments. Flight orientation to the appropriate food source and mating partner depends on the perception and integration of multiple chemical signals. We used a wind tunnel-based assay to investigate the natural and molecular evolution of free flight …
The peach volatilome modularity is reflected at the genetic and environmental response levels in a QTL mapping population
2014
Background: The improvement of fruit aroma is currently one of the most sought-after objectives in peach breeding programs. To better characterize and assess the genetic potential for increasing aroma quality by breeding, a quantity trait locus (QTL) analysis approach was carried out in an F-1 population segregating largely for fruit traits. Results: Linkage maps were constructed using the IPSC peach 9 K Infinium (R) II array, rendering dense genetic maps, except in the case of certain chromosomes, probably due to identity-by-descent of those chromosomes in the parental genotypes. The variability in compounds associated with aroma was analyzed by a metabolomic approach based on GC-MS to pro…
Dynamics of gene regulatory networks and their dependence on network topology and quantitative parameters – the case of phage λ
2019
Background Gene regulatory networks can be modelled in various ways depending on the level of detail required and biological questions addressed. One of the earliest formalisms used for modeling is a Boolean network, although these models cannot describe most temporal aspects of a biological system. Differential equation models have also been used to model gene regulatory networks, but these frameworks tend to be too detailed for large models and many quantitative parameters might not be deducible in practice. Hybrid models bridge the gap between these two model classes – these are useful when concentration changes are important while the information about precise concentrations and binding…