Investigating biocomplexity through the agent-based paradigm.

Capturing the dynamism that pervades biological systems requires a computational approach that can accommodate both the continuous features of the system environment as well as the flexible and heterogeneous nature of component interactions. This presents a serious challenge for the more traditional mathematical approaches that assume component homogeneity to relate system observables using mathematical equations. While the homogeneity condition does not lead to loss of accuracy while simulating various continua, it fails to offer detailed solutions when applied to systems with dynamically interacting heterogeneous components. As the functionality and architecture of most biological systems is a product of multi-faceted individual interactions at the sub-system level, continuum models rarely offer much beyond qualitative similarity. Agent-based modelling is a class of algorithmic computational approaches that rely on interactions between Turing-complete finite-state machines--or agents--to simulate, from the bottom-up, macroscopic properties of a system. In recognizing the heterogeneity condition, they offer suitable ontologies to the system components being modelled, thereby succeeding where their continuum counterparts tend to struggle. Furthermore, being inherently hierarchical, they are quite amenable to coupling with other computational paradigms. The integration of any agent-based framework with continuum models is arguably the most elegant and precise way of representing biological systems. Although in its nascence, agent-based modelling has been utilized to model biological complexity across a broad range of biological scales (from cells to societies). In this article, we explore the reasons that make agent-based modelling the most precise approach to model biological systems that tend to be non-linear and complex

Evolutionary and ecological processes influencing chemical defense variation in an aposematic and mimetic Heliconius butterfly

Chemical defences against predators underlie the evolution of aposematic coloration and mimicry, which are classic examples of adaptive evolution. Surprisingly little is known about the roles of ecological and evolutionary processes maintaining defence variation, and how they may feedback to shape the evolutionary dynamics of species. Cyanogenic Heliconius butterflies exhibit diverse warning color patterns and mimicry, thus providing a useful framework for investigating these questions. We studied intraspecific variation in de novo biosynthesized cyanogenic toxicity and its potential ecological and evolutionary sources in wild populations of Heliconius erato along environmental gradients, in common-garden broods and with feeding treatments. Our results demonstrate substantial intraspecific variation, including detectable variation among broods reared in a common garden. The latter estimate suggests considerable evolutionary potential in this trait, although predicting the response to selection is likely complicated due to the observed skewed distribution of toxicity values and the signatures of maternal contributions to the inheritance of toxicity. Larval diet contributed little to toxicity variation. Furthermore, toxicity profiles were similar along steep rainfall and altitudinal gradients, providing little evidence for these factors explaining variation in biosynthesized toxicity in natural populations. In contrast, there were striking differences in the chemical profiles of H. erato from geographically distant populations, implying potential local adaptation in the acquisition mechanisms and levels of defensive compounds. The results highlight the extensive variation and potential for adaptive evolution in defense traits for aposematic and mimetic species, which may contribute to the high diversity often found in these systems.Peer reviewe

An Evaluation of a Metaheuristic Artificial Immune System for Household Energy Optimization

[EN] Devices in a smart home should be connected in an optimal way; this helps save energy and money. Among numerous optimization models that can be found in the literature, we would like to highlight artificial immune systems, which use special bioinspired algorithms to solve optimization problems effectively. The aim of this work is to present the application of an artificial immune system in the context of different energy optimization problems. Likewise, a case study is performed in which an artificial immune system is incorporated in order to solve an energy management problem in a domestic environment. A thorough analysis of the different strategies is carried out to demonstrate the ability of an artificial immune system to find a successful optima which satisfies the problem constraints

PHYSIOLOGICAL FACTORS AFFECTING THE BACTERICIDAL ACTIVITY OF THE WESTERN FENCE LIZARD (SCELOPORUS OCCIDENTALIS) FOR THE LYME DISEASE SPIROCHETE, BORRELIA BURGDORFERI

The Western Fence Lizard (Sceloporus occidentalis) is a major host of juvenile stages of the Western Black-legged Tick (Ixodes pacificus), which is the vector for the Lyme disease causative spirochete bacterium Borrelia burgdorferi in the western United States. Because S. occidentalis is reservoir incompetent and capable of eliminating spirochetes from infected ticks, it has been implicated as a major factor in the ecology of Lyme disease in the West. Although complement proteins in lizard blood have been established as the borreliacidal factor, no studies have examined intraspecific variability in host lizard borreliacidal capacity. In Chapter 1 of this thesis, we introduce the complexity of the Borrelia burgdorferi transmission cycle and it’s implications for transmission risk. In Chapter 2 we tested the hypothesis that host lizard physiological condition impacts their borreliacidal capacity. Blood plasma of lizards in varying physiological conditions was challenged against cultured B. burgdorferi, and the complement-mediated inactivation of spirochetes was quantified. Adult lizards had higher bactericidal activity than first-year juveniles, suggesting that complement-mediated inactivation develops with maturity and/or exposure to spirochete antigens. Also, bactericidal activity was positively associated with lizard tick load and body condition. Adult lizard sex did not significantly affect spirochete mortality. Lizards from an inland site with little exposure to ticks had higher bactericidal activity than lizards from a coastal population that is heavily parasitized by ticks

Biophysical characterization of affinity maturation in the human response to anthrax vaccine

Affinity maturation increases the affinity of B-cell derived antibodies to their cognate antigens. In this study, we characterized the kinetic, structural, dynamic and thermodynamic evolution of antibodies during affinity maturation. Through single B-cell cell sorting, paired heavy and light chain sequencing, phylogenetic analysis, antibody expression, and physicochemical characterization, we were able to longitudinally analyze the stages of affinity maturation of anti-PA (B.anthracis protective antigen) antibodies. Following repeated immunizations, we observed up to an 10,000-fold increase in antibody affinity, mainly through a decrease in the off-rates. For detailed maturation analysis, we chose three antibodies lying along a single clonal branch--the clone’s unmutated common ancestor (UCA), a medium affinity antibody (MAAb) appearing after second immunization, and a high-affinity antibody (HAAb) appearing after third immunization. Most of the mutations that occur between the UCA and HAAb resulted in key changes to structural conformation. In particular, mutations change residues in the CDR-H3 region inducing the folding of the CDR-loops into a conformation that is more complementary to PA. This advantageous new antibody conformation is preserved in the unbound state, indicating that though the UCA and MAAb appear to use an induced fit and/or conformational selection mechanism, the HAAb is more rigidly lock-and-key. Thermodynamic results support this interpretation. In the first maturation step from UCA to MAAb, enthalpic improvement indicates optimization of noncovalent interactions. The second step from MAAb to HAAb predominantly involves entropic improvement by which the advantageous conformation made accessible in the first step is made more dominant via the narrowing of effectively accessible conformations, which allows better contact with PA. This is also reflected by a less significant improvement in the enthalpic component of PA-binding. Studies examining the evolving protein-dynamic characteristics further support this interpretation. In summary, we observed that a single energetic component is not responsible for increased affinity in the maturation pathways we studied. From UCA to MAAb, affinity increases through optimization of noncovalent interactions. From MAAb to HAAb, affinity increase is achieved through changes that stabilize the favorable conformation in the unbound state. A better understanding of affinity maturation can have implications for antibody engineering and vaccine development

Using MapReduce Streaming for Distributed Life Simulation on the Cloud

Distributed software simulations are indispensable in the study of large-scale life models but often require the use of technically complex lower-level distributed computing frameworks, such as MPI. We propose to overcome the complexity challenge by applying the emerging MapReduce (MR) model to distributed life simulations and by running such simulations on the cloud. Technically, we design optimized MR streaming algorithms for discrete and continuous versions of Conway’s life according to a general MR streaming pattern. We chose life because it is simple enough as a testbed for MR’s applicability to a-life simulations and general enough to make our results applicable to various lattice-based a-life models. We implement and empirically evaluate our algorithms’ performance on Amazon’s Elastic MR cloud. Our experiments demonstrate that a single MR optimization technique called strip partitioning can reduce the execution time of continuous life simulations by 64%. To the best of our knowledge, we are the first to propose and evaluate MR streaming algorithms for lattice-based simulations. Our algorithms can serve as prototypes in the development of novel MR simulation algorithms for large-scale lattice-based a-life models.https://digitalcommons.chapman.edu/scs_books/1014/thumbnail.jp

Cell population heterogeneity and evolution towards drug resistance in cancer: Biological and mathematical assessment, theoretical treatment optimisation

Background Drug-induced drug resistance in cancer has been attributed to diverse biological mechanisms at the individual cell or cell population scale, relying on stochastically or epigenetically varying expression of phenotypes at the single cell level, and on the adaptability of tumours at the cell population level. Scope of review We focus on intra-tumour heterogeneity, namely between-cell variability within cancer cell populations, to account for drug resistance. To shed light on such heterogeneity, we review evolutionary mechanisms that encompass the great evolution that has designed multicellular organisms, as well as smaller windows of evolution on the time scale of human disease. We also present mathematical models used to predict drug resistance in cancer and optimal control methods that can circumvent it in combined therapeutic strategies. Major conclusions Plasticity in cancer cells, i.e., partial reversal to a stem-like status in individual cells and resulting adaptability of cancer cell populations, may be viewed as backward evolution making cancer cell populations resistant to drug insult. This reversible plasticity is captured by mathematical models that incorporate between-cell heterogeneity through continuous phenotypic variables. Such models have the benefit of being compatible with optimal control methods for the design of optimised therapeutic protocols involving combinations of cytotoxic and cytostatic treatments with epigenetic drugs and immunotherapies. General significance Gathering knowledge from cancer and evolutionary biology with physiologically based mathematical models of cell population dynamics should provide oncologists with a rationale to design optimised therapeutic strategies to circumvent drug resistance, that still remains a major pitfall of cancer therapeutics. This article is part of a Special Issue entitled “System Genetics” Guest Editor: Dr. Yudong Cai and Dr. Tao Huang

Structural and organisational conditions for the appearance of a functionally integrated organisation in the transition from prokaryotic to eukaryotic cell

211 p.The concept of functional (or physiological) integration is explanatorily relevant to both biology andphilosophy of biology, but it suffers from two main related problems: first, it is an umbrella termencompassing any causal interdependence of functions, thus being unsuitable for characterisingbiological organisations as physiologic units; secondly, it lacks a unified theoretical framework tounderstand this concept. This PhD thesis aims to investigate the relationship between functionalintegration and biological individuality by studying the nature and the role of physiological integration inone of the major evolutionary transitions: the origin of the eukaryotic cell from the prokaryotic one. Themethodology employed is the so-called ¿organizational approach¿ that combines the descriptive approachof the methodological naturalism with the normative evaluation of the epistemic and practicalconsequences of the theoretical frameworks of life sciences. At the core of this work is the examinationof the physic-chemical and structural-functional conditions that allowed the transformation of aprokaryote into a eukaryotic cell and that determined a very specific kind of functionally integratedorganisation in eukaryotes. The thesis puts forward a theoretical proposal for functional integrationconsisting in the global capacity, enabled by specific spatial constraints, of a biological organisation toperform system-level regulation, spatio-temporal coordination of the parts, and system-levelreproduction. This proposal for functional integration has important consequences for understandingimportant issues of theoretical biology and philosophy of biology, such as biological individuality,biological autonomy, and major transitions in evolution

Structural and organisational conditions for the appearance of a functionally integrated organisation in the transition from prokaryotic to eukaryotic cell

211 p.The concept of functional (or physiological) integration is explanatorily relevant to both biology andphilosophy of biology, but it suffers from two main related problems: first, it is an umbrella termencompassing any causal interdependence of functions, thus being unsuitable for characterisingbiological organisations as physiologic units; secondly, it lacks a unified theoretical framework tounderstand this concept. This PhD thesis aims to investigate the relationship between functionalintegration and biological individuality by studying the nature and the role of physiological integration inone of the major evolutionary transitions: the origin of the eukaryotic cell from the prokaryotic one. Themethodology employed is the so-called ¿organizational approach¿ that combines the descriptive approachof the methodological naturalism with the normative evaluation of the epistemic and practicalconsequences of the theoretical frameworks of life sciences. At the core of this work is the examinationof the physic-chemical and structural-functional conditions that allowed the transformation of aprokaryote into a eukaryotic cell and that determined a very specific kind of functionally integratedorganisation in eukaryotes. The thesis puts forward a theoretical proposal for functional integrationconsisting in the global capacity, enabled by specific spatial constraints, of a biological organisation toperform system-level regulation, spatio-temporal coordination of the parts, and system-levelreproduction. This proposal for functional integration has important consequences for understandingimportant issues of theoretical biology and philosophy of biology, such as biological individuality,biological autonomy, and major transitions in evolution