96,868 research outputs found
Graph Transformation in Molecular Biology
In the beginning, one of the main fields of application of graph transformation was biology, and more specifically morphology. Later, however, it was like if the biological applications had been left aside by the graph transformation community, just to be moved back into the mainstream these very last years with a new interest in molecular biology. In this paper, we review several fields of application of graph grammars in molecular biology, including: the modeling higherdimensional structures of biomolecules, the description of biochemical reactions, the analysis of metabolic pathways, and their potential use in computational systems biology
Principal manifolds and graphs in practice: from molecular biology to dynamical systems
We present several applications of non-linear data modeling, using principal
manifolds and principal graphs constructed using the metaphor of elasticity
(elastic principal graph approach). These approaches are generalizations of the
Kohonen's self-organizing maps, a class of artificial neural networks. On
several examples we show advantages of using non-linear objects for data
approximation in comparison to the linear ones. We propose four numerical
criteria for comparing linear and non-linear mappings of datasets into the
spaces of lower dimension. The examples are taken from comparative political
science, from analysis of high-throughput data in molecular biology, from
analysis of dynamical systems.Comment: 12 pages, 9 figure
Algorithms for Visualizing Phylogenetic Networks
We study the problem of visualizing phylogenetic networks, which are
extensions of the Tree of Life in biology. We use a space filling visualization
method, called DAGmaps, in order to obtain clear visualizations using limited
space. In this paper, we restrict our attention to galled trees and galled
networks and present linear time algorithms for visualizing them as DAGmaps.Comment: Appears in the Proceedings of the 24th International Symposium on
Graph Drawing and Network Visualization (GD 2016
Representing and analysing molecular and cellular function in the computer
Determining the biological function of a myriad of genes, and understanding how they interact to yield a living cell, is the major challenge of the post genome-sequencing era. The complexity of biological systems is such that this cannot be envisaged without the help of powerful computer systems capable of representing and analysing the intricate networks of physical and functional interactions between the different cellular components. In this review we try to provide the reader with an appreciation of where we stand in this regard. We discuss some of the inherent problems in describing the different facets of biological function, give an overview of how information on function is currently represented in the major biological databases, and describe different systems for organising and categorising the functions of gene products. In a second part, we present a new general data model, currently under development, which describes information on molecular function and cellular processes in a rigorous manner. The model is capable of representing a large variety of biochemical processes, including metabolic pathways, regulation of gene expression and signal transduction. It also incorporates taxonomies for categorising molecular entities, interactions and processes, and it offers means of viewing the information at different levels of resolution, and dealing with incomplete knowledge. The data model has been implemented in the database on protein function and cellular processes 'aMAZE' (http://www.ebi.ac.uk/research/pfbp/), which presently covers metabolic pathways and their regulation. Several tools for querying, displaying, and performing analyses on such pathways are briefly described in order to illustrate the practical applications enabled by the model
Identification of functionally related enzymes by learning-to-rank methods
Enzyme sequences and structures are routinely used in the biological sciences
as queries to search for functionally related enzymes in online databases. To
this end, one usually departs from some notion of similarity, comparing two
enzymes by looking for correspondences in their sequences, structures or
surfaces. For a given query, the search operation results in a ranking of the
enzymes in the database, from very similar to dissimilar enzymes, while
information about the biological function of annotated database enzymes is
ignored.
In this work we show that rankings of that kind can be substantially improved
by applying kernel-based learning algorithms. This approach enables the
detection of statistical dependencies between similarities of the active cleft
and the biological function of annotated enzymes. This is in contrast to
search-based approaches, which do not take annotated training data into
account. Similarity measures based on the active cleft are known to outperform
sequence-based or structure-based measures under certain conditions. We
consider the Enzyme Commission (EC) classification hierarchy for obtaining
annotated enzymes during the training phase. The results of a set of sizeable
experiments indicate a consistent and significant improvement for a set of
similarity measures that exploit information about small cavities in the
surface of enzymes
Transfer Functions for Protein Signal Transduction: Application to a Model of Striatal Neural Plasticity
We present a novel formulation for biochemical reaction networks in the
context of signal transduction. The model consists of input-output transfer
functions, which are derived from differential equations, using stable
equilibria. We select a set of 'source' species, which receive input signals.
Signals are transmitted to all other species in the system (the 'target'
species) with a specific delay and transmission strength. The delay is computed
as the maximal reaction time until a stable equilibrium for the target species
is reached, in the context of all other reactions in the system. The
transmission strength is the concentration change of the target species. The
computed input-output transfer functions can be stored in a matrix, fitted with
parameters, and recalled to build discrete dynamical models. By separating
reaction time and concentration we can greatly simplify the model,
circumventing typical problems of complex dynamical systems. The transfer
function transformation can be applied to mass-action kinetic models of signal
transduction. The paper shows that this approach yields significant insight,
while remaining an executable dynamical model for signal transduction. In
particular we can deconstruct the complex system into local transfer functions
between individual species. As an example, we examine modularity and signal
integration using a published model of striatal neural plasticity. The modules
that emerge correspond to a known biological distinction between
calcium-dependent and cAMP-dependent pathways. We also found that overall
interconnectedness depends on the magnitude of input, with high connectivity at
low input and less connectivity at moderate to high input. This general result,
which directly follows from the properties of individual transfer functions,
contradicts notions of ubiquitous complexity by showing input-dependent signal
transmission inactivation.Comment: 13 pages, 5 tables, 15 figure
Dynamic Influence Networks for Rule-based Models
We introduce the Dynamic Influence Network (DIN), a novel visual analytics
technique for representing and analyzing rule-based models of protein-protein
interaction networks. Rule-based modeling has proved instrumental in developing
biological models that are concise, comprehensible, easily extensible, and that
mitigate the combinatorial complexity of multi-state and multi-component
biological molecules. Our technique visualizes the dynamics of these rules as
they evolve over time. Using the data produced by KaSim, an open source
stochastic simulator of rule-based models written in the Kappa language, DINs
provide a node-link diagram that represents the influence that each rule has on
the other rules. That is, rather than representing individual biological
components or types, we instead represent the rules about them (as nodes) and
the current influence of these rules (as links). Using our interactive DIN-Viz
software tool, researchers are able to query this dynamic network to find
meaningful patterns about biological processes, and to identify salient aspects
of complex rule-based models. To evaluate the effectiveness of our approach, we
investigate a simulation of a circadian clock model that illustrates the
oscillatory behavior of the KaiC protein phosphorylation cycle.Comment: Accepted to TVCG, in pres
Single-cell-based system to monitor carrier driven cellular auxin homeostasis
Background: Abundance and distribution of the plant hormone auxin play important roles in plant development. Besides other metabolic processes, various auxin carriers control the cellular level of active auxin and, hence, are major regulators of cellular auxin homeostasis. Despite the developmental importance of auxin transporters, a simple medium-to-high throughput approach to assess carrier activities is still missing. Here we show that carrier driven depletion of cellular auxin correlates with reduced nuclear auxin signaling in tobacco Bright Yellow-2 (BY-2) cell cultures.
Results: We developed an easy to use transient single-cell-based system to detect carrier activity. We use the relative changes in signaling output of the auxin responsive promoter element DR5 to indirectly visualize auxin carrier activity. The feasibility of the transient approach was demonstrated by pharmacological and genetic interference with auxin signaling and transport. As a proof of concept, we provide visual evidence that the prominent auxin transport proteins PIN-FORMED (PIN) 2 and PIN5 regulate cellular auxin homeostasis at the plasma membrane and endoplasmic reticulum (ER), respectively. Our data suggest that PIN2 and PIN5 have different sensitivities to the auxin transport inhibitor 1-naphthylphthalamic acid (NPA). Also the putative PIN-LIKES (PILS) auxin carrier activity at the ER is insensitive to NPA in our system, indicating that NPA blocks intercellular, but not intracellular auxin transport.
Conclusions: This single-cell-based system is a useful tool by which the activity of putative auxin carriers, such as PINs, PILS and WALLS ARE THIN1 (WAT1), can be indirectly visualized in a medium-to-high throughput manner. Moreover, our single cell system might be useful to investigate also other hormonal signaling pathways, such as cytokinin
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