57,353 research outputs found
Reduction of dynamical biochemical reaction networks in computational biology
Biochemical networks are used in computational biology, to model the static
and dynamical details of systems involved in cell signaling, metabolism, and
regulation of gene expression. Parametric and structural uncertainty, as well
as combinatorial explosion are strong obstacles against analyzing the dynamics
of large models of this type. Multi-scaleness is another property of these
networks, that can be used to get past some of these obstacles. Networks with
many well separated time scales, can be reduced to simpler networks, in a way
that depends only on the orders of magnitude and not on the exact values of the
kinetic parameters. The main idea used for such robust simplifications of
networks is the concept of dominance among model elements, allowing
hierarchical organization of these elements according to their effects on the
network dynamics. This concept finds a natural formulation in tropical
geometry. We revisit, in the light of these new ideas, the main approaches to
model reduction of reaction networks, such as quasi-steady state and
quasi-equilibrium approximations, and provide practical recipes for model
reduction of linear and nonlinear networks. We also discuss the application of
model reduction to backward pruning machine learning techniques
Genetic and Neuroanatomical Support for Functional Brain Network Dynamics in Epilepsy
Focal epilepsy is a devastating neurological disorder that affects an
overwhelming number of patients worldwide, many of whom prove resistant to
medication. The efficacy of current innovative technologies for the treatment
of these patients has been stalled by the lack of accurate and effective
methods to fuse multimodal neuroimaging data to map anatomical targets driving
seizure dynamics. Here we propose a parsimonious model that explains how
large-scale anatomical networks and shared genetic constraints shape
inter-regional communication in focal epilepsy. In extensive ECoG recordings
acquired from a group of patients with medically refractory focal-onset
epilepsy, we find that ictal and preictal functional brain network dynamics can
be accurately predicted from features of brain anatomy and geometry, patterns
of white matter connectivity, and constraints complicit in patterns of gene
coexpression, all of which are conserved across healthy adult populations.
Moreover, we uncover evidence that markers of non-conserved architecture,
potentially driven by idiosyncratic pathology of single subjects, are most
prevalent in high frequency ictal dynamics and low frequency preictal dynamics.
Finally, we find that ictal dynamics are better predicted by white matter
features and more poorly predicted by geometry and genetic constraints than
preictal dynamics, suggesting that the functional brain network dynamics
manifest in seizures rely on - and may directly propagate along - underlying
white matter structure that is largely conserved across humans. Broadly, our
work offers insights into the generic architectural principles of the human
brain that impact seizure dynamics, and could be extended to further our
understanding, models, and predictions of subject-level pathology and response
to intervention
Simulating the Mammalian Blastocyst - Molecular and Mechanical Interactions Pattern the Embryo
Mammalian embryogenesis is a dynamic process involving gene expression and mechanical forces between proliferating cells. The exact nature of these interactions, which determine the lineage patterning of the trophectoderm and endoderm tissues occurring in a highly regulated manner at precise periods during the embryonic development, is an area of debate. We have developed a computational modeling framework for studying this process, by which the combined effects of mechanical and genetic interactions are analyzed within the context of proliferating cells. At a purely mechanical level, we demonstrate that the perpendicular alignment of the animal-vegetal (a-v) and embryonic-abembryonic (eb-ab) axes is a result of minimizing the total elastic conformational energy of the entire collection of cells, which are constrained by the zona pellucida. The coupling of gene expression with the mechanics of cell movement is important for formation of both the trophectoderm and the endoderm. In studying the formation of the trophectoderm, we contrast and compare quantitatively two hypotheses: (1) The position determines gene expression, and (2) the gene expression determines the position. Our model, which couples gene expression with mechanics, suggests that differential adhesion between different cell types is a critical determinant in the robust endoderm formation. In addition to differential adhesion, two different testable hypotheses emerge when considering endoderm formation: (1) A directional force acts on certain cells and moves them into forming the endoderm layer, which separates the blastocoel and the cells of the inner cell mass (ICM). In this case the blastocoel simply acts as a static boundary. (2) The blastocoel dynamically applies pressure upon the cells in contact with it, such that cell segregation in the presence of differential adhesion leads to the endoderm formation. To our knowledge, this is the first attempt to combine cell-based spatial mechanical simulations with genetic networks to explain mammalian embryogenesis. Such a framework provides the means to test hypotheses in a controlled in silico environment
Partial differential equations for self-organization in cellular and developmental biology
Understanding the mechanisms governing and regulating the emergence of structure and heterogeneity within cellular systems, such as the developing embryo, represents a multiscale challenge typifying current integrative biology research, namely, explaining the macroscale behaviour of a system from microscale dynamics. This review will focus upon modelling how cell-based dynamics orchestrate the emergence of higher level structure. After surveying representative biological examples and the models used to describe them, we will assess how developments at the scale of molecular biology have impacted on current theoretical frameworks, and the new modelling opportunities that are emerging as a result. We shall restrict our survey of mathematical approaches to partial differential equations and the tools required for their analysis. We will discuss the gap between the modelling abstraction and biological reality, the challenges this presents and highlight some open problems in the field
Dysfunctions of highly parallel real-time machines as 'developmental disorders': Security concerns and a Caveat Emptor
A cognitive paradigm for gene expression in developmental biology that is based on rigorous application of the asymptotic limit theorems of information theory can be adapted to highly parallel real-time computing. The coming Brave New World of massively parallel 'autonomic' and 'Self-X' machines driven by the explosion of multiple core and molecular computing technologies will not be spared patterns of canonical and idiosyncratic failure analogous to the developmental disorders affecting organisms that have had the relentless benefit of a billion years of evolutionary pruning. This paper provides a warning both to potential users of these machines and, given that many such disorders can be induced by external agents, to those concerned with larger scale matters of homeland security
The Price equation program: simple invariances unify population dynamics, thermodynamics, probability, information and inference
The fundamental equations of various disciplines often seem to share the same
basic structure. Natural selection increases information in the same way that
Bayesian updating increases information. Thermodynamics and the forms of common
probability distributions express maximum increase in entropy, which appears
mathematically as loss of information. Physical mechanics follows paths of
change that maximize Fisher information. The information expressions typically
have analogous interpretations as the Newtonian balance between force and
acceleration, representing a partition between direct causes of change and
opposing changes in the frame of reference. This web of vague analogies hints
at a deeper common mathematical structure. I suggest that the Price equation
expresses that underlying universal structure. The abstract Price equation
describes dynamics as the change between two sets. One component of dynamics
expresses the change in the frequency of things, holding constant the values
associated with things. The other component of dynamics expresses the change in
the values of things, holding constant the frequency of things. The separation
of frequency from value generalizes Shannon's separation of the frequency of
symbols from the meaning of symbols in information theory. The Price equation's
generalized separation of frequency and value reveals a few simple invariances
that define universal geometric aspects of change. For example, the
conservation of total frequency, although a trivial invariance by itself,
creates a powerful constraint on the geometry of change. That constraint plus a
few others seem to explain the common structural forms of the equations in
different disciplines. From that abstract perspective, interpretations such as
selection, information, entropy, force, acceleration, and physical work arise
from the same underlying geometry expressed by the Price equation.Comment: Version 3: added figure illustrating geometry; added table of symbols
and two tables summarizing mathematical relations; this version accepted for
publication in Entrop
Mathematics at the eve of a historic transition in biology
A century ago physicists and mathematicians worked in tandem and established
quantum mechanism. Indeed, algebras, partial differential equations, group
theory, and functional analysis underpin the foundation of quantum mechanism.
Currently, biology is undergoing a historic transition from qualitative,
phenomenological and descriptive to quantitative, analytical and predictive.
Mathematics, again, becomes a driving force behind this new transition in
biology.Comment: 5 pages, 2 figure
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