6,283 research outputs found
NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps
Molecular biology knowledge can be systematically represented in a
computer-readable form as a comprehensive map of molecular interactions. There
exist a number of maps of molecular interactions containing detailed
description of various cell mechanisms. It is difficult to explore these large
maps, to comment their content and to maintain them. Though there exist several
tools addressing these problems individually, the scientific community still
lacks an environment that combines these three capabilities together. NaviCell
is a web-based environment for exploiting large maps of molecular interactions,
created in CellDesigner, allowing their easy exploration, curation and
maintenance. NaviCell combines three features: (1) efficient map browsing based
on Google Maps engine; (2) semantic zooming for viewing different levels of
details or of abstraction of the map and (3) integrated web-based blog for
collecting the community feedback. NaviCell can be easily used by experts in
the field of molecular biology for studying molecular entities of their
interest in the context of signaling pathways and cross-talks between pathways
within a global signaling network. NaviCell allows both exploration of detailed
molecular mechanisms represented on the map and a more abstract view of the map
up to a top-level modular representation. NaviCell facilitates curation,
maintenance and updating the comprehensive maps of molecular interactions in an
interactive fashion due to an imbedded blogging system. NaviCell provides an
easy way to explore large-scale maps of molecular interactions, thanks to the
Google Maps and WordPress interfaces, already familiar to many users. Semantic
zooming used for navigating geographical maps is adopted for molecular maps in
NaviCell, making any level of visualization meaningful to the user. In
addition, NaviCell provides a framework for community-based map curation.Comment: 20 pages, 5 figures, submitte
Bethe Ansatz in the Bernoulli Matching Model of Random Sequence Alignment
For the Bernoulli Matching model of sequence alignment problem we apply the
Bethe ansatz technique via an exact mapping to the 5--vertex model on a square
lattice. Considering the terrace--like representation of the sequence alignment
problem, we reproduce by the Bethe ansatz the results for the averaged length
of the Longest Common Subsequence in Bernoulli approximation. In addition, we
compute the average number of nucleation centers of the terraces.Comment: 14 pages, 5 figures (some points are clarified
Can retinal ganglion cell dipoles seed iso-orientation domains in the visual cortex?
It has been argued that the emergence of roughly periodic orientation
preference maps (OPMs) in the primary visual cortex (V1) of carnivores and
primates can be explained by a so-called statistical connectivity model. This
model assumes that input to V1 neurons is dominated by feed-forward projections
originating from a small set of retinal ganglion cells (RGCs). The typical
spacing between adjacent cortical orientation columns preferring the same
orientation then arises via Moir\'{e}-Interference between hexagonal ON/OFF RGC
mosaics. While this Moir\'{e}-Interference critically depends on long-range
hexagonal order within the RGC mosaics, a recent statistical analysis of RGC
receptive field positions found no evidence for such long-range positional
order. Hexagonal order may be only one of several ways to obtain spatially
repetitive OPMs in the statistical connectivity model. Here, we investigate a
more general requirement on the spatial structure of RGC mosaics that can seed
the emergence of spatially repetitive cortical OPMs, namely that angular
correlations between so-called RGC dipoles exhibit a spatial structure similar
to that of OPM autocorrelation functions. Both in cat beta cell mosaics as well
as primate parasol receptive field mosaics we find that RGC dipole angles are
spatially uncorrelated. To help assess the level of these correlations, we
introduce a novel point process that generates mosaics with realistic nearest
neighbor statistics and a tunable degree of spatial correlations of dipole
angles. Using this process, we show that given the size of available data sets,
the presence of even weak angular correlations in the data is very unlikely. We
conclude that the layout of ON/OFF ganglion cell mosaics lacks the spatial
structure necessary to seed iso-orientation domains in the primary visual
cortex.Comment: 9 figures + 1 Supplementary figure and 1 Supplementary tabl
On the entropy of protein families
Proteins are essential components of living systems, capable of performing a
huge variety of tasks at the molecular level, such as recognition, signalling,
copy, transport, ... The protein sequences realizing a given function may
largely vary across organisms, giving rise to a protein family. Here, we
estimate the entropy of those families based on different approaches, including
Hidden Markov Models used for protein databases and inferred statistical models
reproducing the low-order (1-and 2-point) statistics of multi-sequence
alignments. We also compute the entropic cost, that is, the loss in entropy
resulting from a constraint acting on the protein, such as the fixation of one
particular amino-acid on a specific site, and relate this notion to the escape
probability of the HIV virus. The case of lattice proteins, for which the
entropy can be computed exactly, allows us to provide another illustration of
the concept of cost, due to the competition of different folds. The relevance
of the entropy in relation to directed evolution experiments is stressed.Comment: to appear in Journal of Statistical Physic
Multiscale metabolic modeling of C4 plants: connecting nonlinear genome-scale models to leaf-scale metabolism in developing maize leaves
C4 plants, such as maize, concentrate carbon dioxide in a specialized
compartment surrounding the veins of their leaves to improve the efficiency of
carbon dioxide assimilation. Nonlinear relationships between carbon dioxide and
oxygen levels and reaction rates are key to their physiology but cannot be
handled with standard techniques of constraint-based metabolic modeling. We
demonstrate that incorporating these relationships as constraints on reaction
rates and solving the resulting nonlinear optimization problem yields realistic
predictions of the response of C4 systems to environmental and biochemical
perturbations. Using a new genome-scale reconstruction of maize metabolism, we
build an 18000-reaction, nonlinearly constrained model describing mesophyll and
bundle sheath cells in 15 segments of the developing maize leaf, interacting
via metabolite exchange, and use RNA-seq and enzyme activity measurements to
predict spatial variation in metabolic state by a novel method that optimizes
correlation between fluxes and expression data. Though such correlations are
known to be weak in general, here the predicted fluxes achieve high correlation
with the data, successfully capture the experimentally observed base-to-tip
transition between carbon-importing tissue and carbon-exporting tissue, and
include a nonzero growth rate, in contrast to prior results from similar
methods in other systems. We suggest that developmental gradients may be
particularly suited to the inference of metabolic fluxes from expression data.Comment: 57 pages, 14 figures; submitted to PLoS Computational Biology; source
code available at http://github.com/ebogart/fluxtools and
http://github.com/ebogart/multiscale_c4_sourc
A simple mechanistic model of sprout spacing in tumour-associated angiogenesis
This paper develops a simple mathematical model of the siting of capillary sprouts on an existing blood vessel during the initiation of tumour-induced angiogenesis. The model represents an inceptive attempt to address the question of how unchecked sprouting of the parent vessel is avoided at the initiation of angiogenesis, based on the idea that feedback regulation processes play the dominant role. No chemical interaction between the proangiogenic and antiangiogenic factors is assumed. The model is based on corneal pocket experiments, and provides a mathematical analysis of the initial spacing of angiogenic sprouts
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