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

From Simple to Complex and Ultra-complex Systems:\ud A Paradigm Shift Towards Non-Abelian Systems Dynamics

Atoms, molecules, organisms distinguish layers of reality because of the causal links that govern their behavior, both horizontally (atom-atom, molecule-molecule, organism-organism) and vertically (atom-molecule-organism). This is the first intuition of the theory of levels. Even if the further development of the theory will require imposing a number of qualifications to this initial intuition, the idea of a series of entities organized on different levels of complexity will prove correct. Living systems as well as social systems and the human mind present features remarkably different from those characterizing non-living, simple physical and chemical systems. We propose that super-complexity requires at least four different categorical frameworks, provided by the theories of levels of reality, chronotopoids, (generalized) interactions, and anticipation

From Simple to Complex and Ultra-complex Systems:\ud A Paradigm Shift Towards Non-Abelian Systems Dynamics

Atoms, molecules, organisms distinguish layers of reality because of the causal links that govern their behavior, both horizontally (atom-atom, molecule-molecule, organism-organism) and vertically (atom-molecule-organism). This is the first intuition of the theory of levels. Even if the further development of the theory will require imposing a number of qualifications to this initial intuition, the idea of a series of entities organized on different levels of complexity will prove correct. Living systems as well as social systems and the human mind present features remarkably different from those characterizing non-living, simple physical and chemical systems. We propose that super-complexity requires at least four different categorical frameworks, provided by the theories of levels of reality, chronotopoids, (generalized) interactions, and anticipation

Categorical Ontology of Complex Systems, Meta-Systems and Theory of Levels: The Emergence of Life, Human Consciousness and Society

Single cell interactomics in simpler organisms, as well as somatic cell interactomics in multicellular organisms, involve biomolecular interactions in complex signalling pathways that were recently represented in modular terms by quantum automata with ‘reversible behavior’ representing normal cell cycling and division. Other implications of such quantum automata, modular modeling of signaling pathways and cell differentiation during development are in the fields of neural plasticity and brain development leading to quantum-weave dynamic patterns and specific molecular processes underlying extensive memory, learning, anticipation mechanisms and the emergence of human consciousness during the early brain development in children. Cell interactomics is here represented for the first time as a mixture of ‘classical’ states that determine molecular dynamics subject to Boltzmann statistics and ‘steady-state’, metabolic (multi-stable) manifolds, together with ‘configuration’ spaces of metastable quantum states emerging from complex quantum dynamics of interacting networks of biomolecules, such as proteins and nucleic acids that are now collectively defined as quantum interactomics. On the other hand, the time dependent evolution over several generations of cancer cells --that are generally known to undergo frequent and extensive genetic mutations and, indeed, suffer genomic transformations at the chromosome level (such as extensive chromosomal aberrations found in many colon cancers)-- cannot be correctly represented in the ‘standard’ terms of quantum automaton modules, as the normal somatic cells can. This significant difference at the cancer cell genomic level is therefore reflected in major changes in cancer cell interactomics often from one cancer cell ‘cycle’ to the next, and thus it requires substantial changes in the modeling strategies, mathematical tools and experimental designs aimed at understanding cancer mechanisms. Novel solutions to this important problem in carcinogenesis are proposed and experimental validation procedures are suggested. From a medical research and clinical standpoint, this approach has important consequences for addressing and preventing the development of cancer resistance to medical therapy in ongoing clinical trials involving stage III cancer patients, as well as improving the designs of future clinical trials for cancer treatments.\ud \ud \ud KEYWORDS: Emergence of Life and Human Consciousness;\ud Proteomics; Artificial Intelligence; Complex Systems Dynamics; Quantum Automata models and Quantum Interactomics; quantum-weave dynamic patterns underlying human consciousness; specific molecular processes underlying extensive memory, learning, anticipation mechanisms and human consciousness; emergence of human consciousness during the early brain development in children; Cancer cell ‘cycling’; interacting networks of proteins and nucleic acids; genetic mutations and chromosomal aberrations in cancers, such as colon cancer; development of cancer resistance to therapy; ongoing clinical trials involving stage III cancer patients’ possible improvements of the designs for future clinical trials and cancer treatments. \ud \u