23,086 research outputs found
Mathematical modelling plant signalling networks
During the last two decades, molecular genetic studies and the completion of the sequencing of the Arabidopsis thaliana genome have increased knowledge of hormonal regulation in plants. These signal transduction pathways act in concert through gene regulatory and signalling networks whose main components have begun to be elucidated. Our understanding of the resulting cellular processes is hindered by the complex, and sometimes counter-intuitive, dynamics of the networks, which may be interconnected through feedback controls and cross-regulation. Mathematical modelling provides a valuable tool to investigate such dynamics and to perform in silico experiments that may not be easily carried out in a laboratory. In this article, we firstly review general methods for modelling gene and signalling networks and their application in plants. We then describe specific models of hormonal perception and cross-talk in plants. This sub-cellular analysis paves the way for more comprehensive mathematical studies of hormonal transport and signalling in a multi-scale setting
Bayesian variable selection and data integration for biological regulatory networks
A substantial focus of research in molecular biology are gene regulatory
networks: the set of transcription factors and target genes which control the
involvement of different biological processes in living cells. Previous
statistical approaches for identifying gene regulatory networks have used gene
expression data, ChIP binding data or promoter sequence data, but each of these
resources provides only partial information. We present a Bayesian hierarchical
model that integrates all three data types in a principled variable selection
framework. The gene expression data are modeled as a function of the unknown
gene regulatory network which has an informed prior distribution based upon
both ChIP binding and promoter sequence data. We also present a variable
weighting methodology for the principled balancing of multiple sources of prior
information. We apply our procedure to the discovery of gene regulatory
relationships in Saccharomyces cerevisiae (Yeast) for which we can use several
external sources of information to validate our results. Our inferred
relationships show greater biological relevance on the external validation
measures than previous data integration methods. Our model also estimates
synergistic and antagonistic interactions between transcription factors, many
of which are validated by previous studies. We also evaluate the results from
our procedure for the weighting for multiple sources of prior information.
Finally, we discuss our methodology in the context of previous approaches to
data integration and Bayesian variable selection.Comment: Published in at http://dx.doi.org/10.1214/07-AOAS130 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Application of new probabilistic graphical models in the genetic regulatory networks studies
This paper introduces two new probabilistic graphical models for
reconstruction of genetic regulatory networks using DNA microarray data. One is
an Independence Graph (IG) model with either a forward or a backward search
algorithm and the other one is a Gaussian Network (GN) model with a novel
greedy search method. The performances of both models were evaluated on four
MAPK pathways in yeast and three simulated data sets. Generally, an IG model
provides a sparse graph but a GN model produces a dense graph where more
information about gene-gene interactions is preserved. Additionally, we found
two key limitations in the prediction of genetic regulatory networks using DNA
microarray data, the first is the sufficiency of sample size and the second is
the complexity of network structures may not be captured without additional
data at the protein level. Those limitations are present in all prediction
methods which used only DNA microarray data.Comment: 38 pages, 3 figure
The tapeworm interactome: inferring confidence scored protein-protein interactions from the proteome of Hymenolepis microstoma
BACKGROUND: Reference genome and transcriptome assemblies of helminths have reached a level of completion whereby secondary analyses that rely on accurate gene estimation or syntenic relationships can be now conducted with a high level of confidence. Recent public release of the v.3 assembly of the mouse bile-duct tapeworm, Hymenolepis microstoma, provides chromosome-level characterisation of the genome and a stabilised set of protein coding gene models underpinned by bioinformatic and empirical data. However, interactome data have not been produced. Conserved protein-protein interactions in other organisms, termed interologs, can be used to transfer interactions between species, allowing systems-level analysis in non-model organisms.
RESULTS: Here, we describe a probabilistic, integrated network of interologs for the H. microstoma proteome, based on conserved protein interactions found in eukaryote model species. Almost a third of the 10,139 gene models in the v.3 assembly could be assigned interaction data and assessment of the resulting network indicates that topologically-important proteins are related to essential cellular pathways, and that the network clusters into biologically meaningful components. Moreover, network parameters are similar to those of single-species interaction networks that we constructed in the same way for S. cerevisiae, C. elegans and H. sapiens, demonstrating that information-rich, system-level analyses can be conducted even on species separated by a large phylogenetic distance from the major model organisms from which most protein interaction evidence is based. Using the interolog network, we then focused on sub-networks of interactions assigned to discrete suites of genes of interest, including signalling components and transcription factors, germline multipotency genes, and genes differentially-expressed between larval and adult worms. Results show not only an expected bias toward highly-conserved proteins, such as components of intracellular signal transduction, but in some cases predicted interactions with transcription factors that aid in identifying their target genes.
CONCLUSIONS: With key helminth genomes now complete, systems-level analyses can provide an important predictive framework to guide basic and applied research on helminths and will become increasingly informative as new protein-protein interaction data accumulate
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