Integrating metabolic networks at the cellular scale into physiologically based pharmacokinetic models at the organism level allows the mechanistic description of drug action, pathogenesis, or adverse events across multiple layers of biological organization. Such multiscale approaches therefore provide the opportunity for novel rational approaches in medical diagnostics and pharmaceutical drug development. The figure illustrates a schematic overview of the approach used in Krauss et al.
Image Credit: Stephan Schaller, Markus Krauss, and Lars Kuepfer.
Editorials
A Future Vision for PLOS Computational Biology
PLOS Computational Biology: published October 4, 2012 | https://doi.org/10.1371/journal.pcbi.1002727
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Seven Years; It's Time for a Change
PLOS Computational Biology: published October 4, 2012 | https://doi.org/10.1371/journal.pcbi.1002728
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Research Articles
Predictive Dynamics of Human Pain Perception
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How Recent History Affects Perception: The Normative Approach and Its Heuristic Approximation
PLOS Computational Biology: published October 25, 2012 | https://doi.org/10.1371/journal.pcbi.1002731
The Effect of Bacterial Recombination on Adaptation on Fitness Landscapes with Limited Peak Accessibility
PLOS Computational Biology: published October 25, 2012 | https://doi.org/10.1371/journal.pcbi.1002735
Next-Generation Sequencing of Human Mitochondrial Reference Genomes Uncovers High Heteroplasmy Frequency
PLOS Computational Biology: published October 25, 2012 | https://doi.org/10.1371/journal.pcbi.1002737
The Role of Social Contacts and Original Antigenic Sin in Shaping the Age Pattern of Immunity to Seasonal Influenza
PLOS Computational Biology: published October 25, 2012 | https://doi.org/10.1371/journal.pcbi.1002741
Modeling Protective Anti-Tumor Immunity via Preventative Cancer Vaccines Using a Hybrid Agent-based and Delay Differential Equation Approach
PLOS Computational Biology: published October 25, 2012 | https://doi.org/10.1371/journal.pcbi.1002742
Incorporating 16S Gene Copy Number Information Improves Estimates of Microbial Diversity and Abundance
PLOS Computational Biology: published October 25, 2012 | https://doi.org/10.1371/journal.pcbi.1002743
Evolutionary Analysis of Human Immunodeficiency Virus Type 1 Therapies Based on Conditionally Replicating Vectors
PLOS Computational Biology: published October 25, 2012 | https://doi.org/10.1371/journal.pcbi.1002744
Emergence of the Mitochondrial Reticulum from Fission and Fusion Dynamics
PLOS Computational Biology: published October 25, 2012 | https://doi.org/10.1371/journal.pcbi.1002745
Integrating Cellular Metabolism into a Multiscale Whole-Body Model
PLOS Computational Biology: published October 25, 2012 | https://doi.org/10.1371/journal.pcbi.1002750
Multiple Spike Time Patterns Occur at Bifurcation Points of Membrane Potential Dynamics
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002615
Evaluating the Adequacy of Gravity Models as a Description of Human Mobility for Epidemic Modelling
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002699
Osteoprotegerin in Bone Metastases: Mathematical Solution to the Puzzle
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002703
CAVER 3.0: A Tool for the Analysis of Transport Pathways in Dynamic Protein Structures
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002708
Probability Fluxes and Transition Paths in a Markovian Model Describing Complex Subunit Cooperativity in HCN2 Channels
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002721
Spatially Pooled Contrast Responses Predict Neural and Perceptual Similarity of Naturalistic Image Categories
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002726
The Dynamics of Naturally Acquired Immunity to Plasmodium falciparum Infection
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002729
Estimating the Hidden Burden of Bovine Tuberculosis in Great Britain
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002730
Linkers of Cell Polarity and Cell Cycle Regulation in the Fission Yeast Protein Interaction Network
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002732
The Laminar Cortex Model: A New Continuum Cortex Model Incorporating Laminar Architecture
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002733
Regulatory Network Structure as a Dominant Determinant of Transcription Factor Evolutionary Rate
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002734
Membrane-Elasticity Model of Coatless Vesicle Budding Induced by ESCRT Complexes
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002736
A Structural Systems Biology Approach for Quantifying the Systemic Consequences of Missense Mutations in Proteins
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002738
Phasic Firing in Vasopressin Cells: Understanding Its Functional Significance through Computational Models
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002740
Determining Host Metabolic Limitations on Viral Replication via Integrated Modeling and Experimental Perturbation
PLOS Computational Biology: published October 18, 2012 | https://doi.org/10.1371/journal.pcbi.1002746
Connecting Macroscopic Observables and Microscopic Assembly Events in Amyloid Formation Using Coarse Grained Simulations
PLOS Computational Biology: published October 11, 2012 | https://doi.org/10.1371/journal.pcbi.1002692
Discovering Relations Between Mind, Brain, and Mental Disorders Using Topic Mapping
PLOS Computational Biology: published October 11, 2012 | https://doi.org/10.1371/journal.pcbi.1002707
Analysis of Slow (Theta) Oscillations as a Potential Temporal Reference Frame for Information Coding in Sensory Cortices
PLOS Computational Biology: published October 11, 2012 | https://doi.org/10.1371/journal.pcbi.1002717
Very Slow Search and Reach: Failure to Maximize Expected Gain in an Eye-Hand Coordination Task
PLOS Computational Biology: published October 11, 2012 | https://doi.org/10.1371/journal.pcbi.1002718
Functional Modules, Structural Topology, and Optimal Activity in Metabolic Networks
PLOS Computational Biology: published October 11, 2012 | https://doi.org/10.1371/journal.pcbi.1002720
Modeling Dynamic Regulatory Processes in Stroke
PLOS Computational Biology: published October 11, 2012 | https://doi.org/10.1371/journal.pcbi.1002722
MOSAIC: A Multiscale Model of Osteogenesis and Sprouting Angiogenesis with Lateral Inhibition of Endothelial Cells
PLOS Computational Biology: published October 11, 2012 | https://doi.org/10.1371/journal.pcbi.1002724
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Prediction and Dissection of Widely-Varying Association Rate Constants of Actin-Binding Proteins
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Ubiquitin Dynamics in Complexes Reveal Molecular Recognition Mechanisms Beyond Induced Fit and Conformational Selection
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Disease-Associated Mutations Disrupt Functionally Important Regions of Intrinsic Protein Disorder
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Molecular Mechanism for the Dual Alcohol Modulation of Cys-loop Receptors
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Random Field Model Reveals Structure of the Protein Recombinational Landscape
PLOS Computational Biology: published October 4, 2012 | https://doi.org/10.1371/journal.pcbi.1002713
A Model of Reward- and Effort-Based Optimal Decision Making and Motor Control
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