52,002 research outputs found
Computational Methods for Identification and Modelling of Complex Biological Systems
3 pages,-- Editorial.-- This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedMathematical and computational models are key tools for
understanding biological phenomena. In the last decades,
scientific and technological advances have facilitated their
evergrowing adoption in biologically oriented research. The
strongly interdisciplinary character of these areas, in which
biologistswork alongwith researchers fromphysical sciences,
engineering, and medicine, fosters the cross-fertilization
between scientific fields. However, the large degree of structural
and parametric uncertainty typically associated with
biological processesmakes it nontrivial to analyze them using
techniques imported from fields in which these issues are
less prevalent. Thus, there is a need for new methodological
developments that fill this gap. The present special issue
addresses this need by providing an overview of current open
problems and presenting recent results regarding mathematical
inference and modelling of biological systemsPeer reviewe
Instantaneous modelling and reverse engineering of data-consistent prime models in seconds!
A theoretical framework that supports automated construction of dynamic prime models purely from experimental time series data has been invented and developed, which can automatically generate (construct) data-driven models of any time series data in seconds. This has resulted in the formulation and formalisation of new reverse engineering and dynamic methods for automated systems modelling of complex systems, including complex biological, financial, control, and artificial neural network systems. The systems/model theory behind the invention has been formalised as a new, effective and robust system identification strategy complementary to process-based modelling. The proposed dynamic modelling and network inference solutions often involve tackling extremely difficult parameter estimation challenges, inferring unknown underlying network structures, and unsupervised formulation and construction of smart and intelligent ODE models of complex systems. In underdetermined conditions, i.e., cases of dealing with how best to instantaneously and rapidly construct data-consistent prime models of unknown (or well-studied) complex system from small-sized time series data, inference of unknown underlying network of interaction is more challenging. This article reports a robust step-by-step mathematical and computational analysis of the entire prime model construction process that determines a model from data in less than a minute
Cyclin-dependent kinases as drug targets for cell growth and proliferation disorders. A role for systems biology approach in drug development. Part II - CDKs as drug targets in hypertrophic cell growth. Modelling of drugs targeting CDKs
Cyclin-dependent kinases (CDKs) are key regulators of cell growth and proliferation. Impaired regulation of their activity leads to various diseases such as cancer and heart hypertrophy. Consequently, a number of CDKs are considered as targets for drug discovery. We review the development of inhibitors of CDK2 as anti-cancer drugs in the first part of the paper and in the second part, respectively, the development of inhibitors of CDK9 as potential therapeutics for heart hypertrophy. We argue that the above diseases are systems biology, or network diseases. In order to fully understand the complexity of the cell growth and proliferation disorders, in addition to experimental sciences, a systems biology approach, involving mathematical and computational modelling ought to be employed
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
Engineering simulations for cancer systems biology
Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions
Qualitative System Identification from Imperfect Data
Experience in the physical sciences suggests that the only realistic means of
understanding complex systems is through the use of mathematical models.
Typically, this has come to mean the identification of quantitative models
expressed as differential equations. Quantitative modelling works best when the
structure of the model (i.e., the form of the equations) is known; and the
primary concern is one of estimating the values of the parameters in the model.
For complex biological systems, the model-structure is rarely known and the
modeler has to deal with both model-identification and parameter-estimation. In
this paper we are concerned with providing automated assistance to the first of
these problems. Specifically, we examine the identification by machine of the
structural relationships between experimentally observed variables. These
relationship will be expressed in the form of qualitative abstractions of a
quantitative model. Such qualitative models may not only provide clues to the
precise quantitative model, but also assist in understanding the essence of
that model. Our position in this paper is that background knowledge
incorporating system modelling principles can be used to constrain effectively
the set of good qualitative models. Utilising the model-identification
framework provided by Inductive Logic Programming (ILP) we present empirical
support for this position using a series of increasingly complex artificial
datasets. The results are obtained with qualitative and quantitative data
subject to varying amounts of noise and different degrees of sparsity. The
results also point to the presence of a set of qualitative states, which we
term kernel subsets, that may be necessary for a qualitative model-learner to
learn correct models. We demonstrate scalability of the method to biological
system modelling by identification of the glycolysis metabolic pathway from
data
Machine Learning and Integrative Analysis of Biomedical Big Data.
Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues
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