894 research outputs found
Data-driven modelling of biological multi-scale processes
Biological processes involve a variety of spatial and temporal scales. A
holistic understanding of many biological processes therefore requires
multi-scale models which capture the relevant properties on all these scales.
In this manuscript we review mathematical modelling approaches used to describe
the individual spatial scales and how they are integrated into holistic models.
We discuss the relation between spatial and temporal scales and the implication
of that on multi-scale modelling. Based upon this overview over
state-of-the-art modelling approaches, we formulate key challenges in
mathematical and computational modelling of biological multi-scale and
multi-physics processes. In particular, we considered the availability of
analysis tools for multi-scale models and model-based multi-scale data
integration. We provide a compact review of methods for model-based data
integration and model-based hypothesis testing. Furthermore, novel approaches
and recent trends are discussed, including computation time reduction using
reduced order and surrogate models, which contribute to the solution of
inference problems. We conclude the manuscript by providing a few ideas for the
development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and
Multiscale Dynamics (American Scientific Publishers
Delineating Parameter Unidentifiabilities in Complex Models
Scientists use mathematical modelling to understand and predict the
properties of complex physical systems. In highly parameterised models there
often exist relationships between parameters over which model predictions are
identical, or nearly so. These are known as structural or practical
unidentifiabilities, respectively. They are hard to diagnose and make reliable
parameter estimation from data impossible. They furthermore imply the existence
of an underlying model simplification. We describe a scalable method for
detecting unidentifiabilities, and the functional relations defining them, for
generic models. This allows for model simplification, and appreciation of which
parameters (or functions thereof) cannot be estimated from data. Our algorithm
can identify features such as redundant mechanisms and fast timescale
subsystems, as well as the regimes in which such approximations are valid. We
base our algorithm on a novel quantification of regional parametric
sensitivity: multiscale sloppiness. Traditionally, the link between parametric
sensitivity and the conditioning of the parameter estimation problem is made
locally, through the Fisher Information Matrix. This is valid in the regime of
infinitesimal measurement uncertainty. We demonstrate the duality between
multiscale sloppiness and the geometry of confidence regions surrounding
parameter estimates made where measurement uncertainty is non-negligible.
Further theoretical relationships are provided linking multiscale sloppiness to
the Likelihood-ratio test. From this, we show that a local sensitivity analysis
(as typically done) is insufficient for determining the reliability of
parameter estimation, even with simple (non)linear systems. Our algorithm
provides a tractable alternative. We finally apply our methods to a
large-scale, benchmark Systems Biology model of NF-B, uncovering
previously unknown unidentifiabilities
Research and Education in Computational Science and Engineering
Over the past two decades the field of computational science and engineering
(CSE) has penetrated both basic and applied research in academia, industry, and
laboratories to advance discovery, optimize systems, support decision-makers,
and educate the scientific and engineering workforce. Informed by centuries of
theory and experiment, CSE performs computational experiments to answer
questions that neither theory nor experiment alone is equipped to answer. CSE
provides scientists and engineers of all persuasions with algorithmic
inventions and software systems that transcend disciplines and scales. Carried
on a wave of digital technology, CSE brings the power of parallelism to bear on
troves of data. Mathematics-based advanced computing has become a prevalent
means of discovery and innovation in essentially all areas of science,
engineering, technology, and society; and the CSE community is at the core of
this transformation. However, a combination of disruptive
developments---including the architectural complexity of extreme-scale
computing, the data revolution that engulfs the planet, and the specialization
required to follow the applications to new frontiers---is redefining the scope
and reach of the CSE endeavor. This report describes the rapid expansion of CSE
and the challenges to sustaining its bold advances. The report also presents
strategies and directions for CSE research and education for the next decade.Comment: Major revision, to appear in SIAM Revie
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