94 research outputs found
Periodic pattern detection in sparse boolean sequences
<p>Abstract</p> <p>Background</p> <p>The specific position of functionally related genes along the DNA has been shown to reflect the interplay between chromosome structure and genetic regulation. By investigating the statistical properties of the distances separating such genes, several studies have highlighted various periodic trends. In many cases, however, groups built up from co-functional or co-regulated genes are small and contain wrong information (data contamination) so that the statistics is poorly exploitable. In addition, gene positions are not expected to satisfy a perfectly ordered pattern along the DNA. Within this scope, we present an algorithm that aims to highlight periodic patterns in sparse boolean sequences, i.e. sequences of the type 010011011010... where the ratio of the number of 1's (denoting here the transcription start of a gene) to 0's is small.</p> <p>Results</p> <p>The algorithm is particularly robust with respect to strong signal distortions such as the addition of 1's at arbitrary positions (contaminated data), the deletion of existing 1's in the sequence (missing data) and the presence of disorder in the position of the 1's (noise). This robustness property stems from an appropriate exploitation of the remarkable alignment properties of periodic points in solenoidal coordinates.</p> <p>Conclusions</p> <p>The efficiency of the algorithm is demonstrated in situations where standard Fourier-based spectral methods are poorly adapted. We also show how the proposed framework allows to identify the 1's that participate in the periodic trends, i.e. how the framework allows to allocate a <it>positional score </it>to genes, in the same spirit of the sequence score. The software is available for public use at <url>http://www.issb.genopole.fr/MEGA/Softwares/iSSB_SolenoidalApplication.zip</url>.</p
Challenges in experimental data integration within genome-scale metabolic models
A report of the meeting "Challenges in experimental data integration within
genome-scale metabolic models", Institut Henri Poincar\'e, Paris, October 10-11
2009, organized by the CNRS-MPG joint program in Systems Biology.Comment: 5 page
Incremental and unifying modelling formalism for biological interaction networks
International audienc
Spatial and topological organization of DNA chains induced by gene co-localization
Transcriptional activity has been shown to relate to the organization of
chromosomes in the eukaryotic nucleus and in the bacterial nucleoid. In
particular, highly transcribed genes, RNA polymerases and transcription factors
gather into discrete spatial foci called transcription factories. However, the
mechanisms underlying the formation of these foci and the resulting topological
order of the chromosome remain to be elucidated. Here we consider a
thermodynamic framework based on a worm-like chain model of chromosomes where
sparse designated sites along the DNA are able to interact whenever they are
spatially close-by. This is motivated by recurrent evidence that there exists
physical interactions between genes that operate together. Three important
results come out of this simple framework. First, the resulting formation of
transcription foci can be viewed as a micro-phase separation of the interacting
sites from the rest of the DNA. In this respect, a thermodynamic analysis
suggests transcription factors to be appropriate candidates for mediating the
physical interactions between genes. Next, numerical simulations of the polymer
reveal a rich variety of phases that are associated with different topological
orderings, each providing a way to increase the local concentrations of the
interacting sites. Finally, the numerical results show that both
one-dimensional clustering and periodic location of the binding sites along the
DNA, which have been observed in several organisms, make the spatial
co-localization of multiple families of genes particularly efficient.Comment: Figures and Supplementary Material freely available on
http://dx.doi.org/10.1371/journal.pcbi.100067
CTCF-mediated transcriptional regulation through cell type-specific chromosome organization in the {\beta}-globin locus
The principles underlying the architectural landscape of chromatin beyond the
nucleosome level in living cells remains largely unknown despite its potential
to play a role in mammalian gene regulation. We investigated the 3-dimensional
folding of a 1 Mbp region of human chromosome 11 containing the {\beta}-globin
genes by integrating looping interactions of the insulator protein CTCF
determined comprehensively by chromosome conformation capture (3C) into a
polymer model of chromatin. We find that CTCF-mediated cell type specific
interactions in erythroid cells are organized to favor contacts known to occur
in vivo between the {\beta}-globin locus control region (LCR) and genes. In
these cells, the modeled {\beta}-globin domain folds into a globule with the
LCR and the active globin genes on the periphery. By contrast, in non-erythroid
cells, the globule is less compact with few but dominant CTCF interactions
driving the genes away from the LCR. This leads to a decrease in contact
frequencies that can exceed 1000-fold depending on the stiffness of the
chromatin and the exact positioning of the genes. Our findings show that an
ensemble of CTCF contacts functionally affects spatial distances between
control elements and target genes contributing to chromosomal organization
required for transcription.Comment: Full article, including Supp. Mat., is available at Nucleic Acids
Research, doi: 10.1093/nar/gks53
Modelling of complex biological systems in the context of genomics: an account of a multidisciplinary thematic seminar held in Montpellier (France) in April 2005
International audienceno abstrac
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