Computational Models of Intracellular and Intercellular Processes in Developmental Biology

Systems biology takes a holistic approach to biological questions as it applies mathematical modeling to link and understand the interaction of components in complex biological systems. Multiscale modeling is the only method that can fully accomplish this aim. Mutliscale models consider processes at different levels that are coupled within the modeling framework. A first requirement in creating such models is a clear understanding of processes that operate at each level. This research focuses on modeling aspects of biological development as a complex process that occurs at many scales. Two of these scales were considered in this work: cellular differentiation, the process of in which less specialized cells acquired specialized properties of mature cell types, and morphogenesis, the process in which an organism develops its shape and tissue architecture. In development, cellular differentiation typically is required for morphogenesis. Therefore, cellular differentiation is at a lower scale than morphogenesis in the overall process of development. In this work, cellular differentiation and morphogenesis were modeled in a variety of biological contexts, with the ultimate goal of linking these different scales of developmental events into a unified model of development. Three aspects of cellular differentiation were investigated, all united by the theme of how the dynamics of gene regulatory networks (GRNs) control differentiation. Two of the projects of this dissertation studied the effect of noise and robustness in switching between cell types during differentiation, and a third deals with the evaluation of hypothetical GRNs that allow the differentiation of specific cell types. All these projects view cell types as high-dimensional attractors in the GRNs and use random Boolean networks as the modeling framework for studying network dynamics. Morphogenesis was studied using the emergence of three-dimensional structures in biofilms as a relatively simple model. Many strains of bacteria form complex structures during growth as colonies on a solid medium. The morphogenesis of these structures was modeled using an agent-based framework and the outcomes were validated using structures of biofilm colonies reported in the literature

Anesthesia management in a pediatric patient with Prune belly syndrome; a case report

Prune belly syndrome (PBS) is a rare congenital disorder, consists of three symptoms: anterior abdominal muscle deficiency, cryptorchidism, and genitourinary malformation. These patients have cardiovascular and musculoskeletal abnormalities, mental retardation, chest deformities, and scoliosis that lead to pulmonary dysfunction. Anesthesia plan in patient needs to rule out any anomalies. For airway management, Laryngeal mask airway (LMA) should be preferred to avoid the use of muscle relaxants. The use of short-acting anesthetics can accelerate recovery from anesthesia.  To reduce postoperative pain, regional techniques are preferred. We report a 6-month- old boy with PBS, and its airway management and anesthesia during surgery

Anesthesia in a pediatric patient with Xeroderma pigmentousoma: A case report

Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder with the following conditions: neurologic disorders that gradually progress and skin hypersensitivity to ultraviolet (UV). Inhalational anesthetic drugs should be avoided in these patients since they may induce DNA damage, also use of muscle relaxants should be kept to a minimum. Thus for XP patients, total intravenous anesthesia (TIVA) is more appropriate for inducing general anesthesia and airway manipulation must be kept to a minimum. We report a 6 year old boy with XP and its airway management and anesthesia during surger

Sensitivity analysis of energy inputs in crop production using artificial neural networks

Sensitivity analysis establishes priorities for research and allows to identify and rank the most important factors which lead to great improvements in output factors. The aim of this study is to examine sensitivity analysis of inputs in grape production. We are proposing to perform sensitivity analysis using partial rank correlation coefficient (PRCC) which is the most reliable and efficient method, and we apply this for the first time in crop production. This research investigates the use of energy in the vineyard of a semi-arid zone of Iran. Energy use efficiency, energy productivity, specific energy and net energy were calculated. Various artificial neural network (ANN) models were developed to predict grape yield with respect to input energies. ANN models consist of a multilayer perceptron (MLP) with seven neurons in the input layer, one and two hidden layer(s) with different number of neurons, and an output layer with one neuron. Input energies were labor, machinery, chemicals, farmyard manure (FYM), diesel, electricity and water for irrigation. Sensitivity analysis was performed on over 100 samples of parameter space generated by Latin hypercube sampling method, which was then fed to the ANN model to predict the yield for each sample. The PRCC between the predicted yield and each parameter value (input) was used to calculate the sensitivity of the model to each input. Results of sensitivity analysis showed that machinery had the greatest impact on grape yield followed by diesel fuel and labor

MultiCellDS : a community-developed standard for curating microenvironment-dependent multicellular data

Exchanging and understanding scientific data and their context represents a significant barrier to advancing research, especially with respect to information siloing. Maintaining information provenance and providing data curation and quality control help overcome common concerns and barriers to the effective sharing of scientific data. To address these problems in and the unique challenges of multicellular systems, we assembled a panel composed of investigators from several disciplines to create the MultiCellular Data Standard (MultiCellDS) with a use-case driven development process. The standard includes (1) digital cell lines, which are analogous to traditional biological cell lines, to record metadata, cellular microenvironment, and cellular phenotype variables of a biological cell line, (2) digital snapshots to consistently record simulation, experimental, and clinical data for multicellular systems, and (3) collections that can logically group digital cell lines and snapshots. We have created a MultiCellular DataBase (MultiCellDB) to store digital snapshots and the 200+ digital cell lines we have generated. MultiCellDS, by having a fixed standard, enables discoverability, extensibility, maintainability, searchability, and sustainability of data, creating biological applicability and clinical utility that permits us to identify upcoming challenges to uplift biology and strategies and therapies for improving human health

第942回千葉医学会例会・第31回肺癌研究施設例会

Example of CellPD’s outputs. This folder contains two examples of the outputs generated by CellPD (using the data from Fig. 2 and Additional file 6). (ZIP 36462 kb

MultiCellDS: a community-developed standard for curating microenvironment-dependent multicellular data

Exchanging and understanding scientific data and their context represents a significant barrier to advancing research, especially with respect to information siloing. Maintaining information provenance and providing data curation and quality control help overcome common concerns and barriers to the effective sharing of scientific data. To address these problems in and the unique challenges of multicellular systems, we assembled a panel composed of investigators from several disciplines to create the MultiCellular Data Standard (MultiCellDS) with a use-case driven development process. The standard includes (1) digital cell lines, which are analogous to traditional biological cell lines, to record metadata, cellular microenvironment, and cellular phenotype variables of a biological cell line, (2) digital snapshots to consistently record simulation, experimental, and clinical data for multicellular systems, and (3) collections that can logically group digital cell lines and snapshots. We have created a MultiCellular DataBase (MultiCellDB) to store digital snapshots and the 200+ digital cell lines we have generated. MultiCellDS, by having a fixed standard, enables discoverability, extensibility, maintainability, searchability, and sustainability of data, creating biological applicability and clinical utility that permits us to identify upcoming challenges to uplift biology and strategies and therapies for improving human health

MultiCellDS: a standard and a community for sharing multicellular data

Cell biology is increasingly focused on cellular heterogeneity and multicellular systems. To make the fullest use of experimental, clinical, and computational efforts, we need standardized data formats, community-curated "public data libraries", and tools to combine and analyze shared data. To address these needs, our multidisciplinary community created MultiCellDS (MultiCellular Data Standard): an extensible standard, a library of digital cell lines and tissue snapshots, and support software. With the help of experimentalists, clinicians, modelers, and data and library scientists, we can grow this seed into a community-owned ecosystem of shared data and tools, to the benefit of basic science, engineering, and human health

Comparing individual-based approaches to modelling the self-organization of multicellular tissues.

The coordinated behaviour of populations of cells plays a central role in tissue growth and renewal. Cells react to their microenvironment by modulating processes such as movement, growth and proliferation, and signalling. Alongside experimental studies, computational models offer a useful means by which to investigate these processes. To this end a variety of cell-based modelling approaches have been developed, ranging from lattice-based cellular automata to lattice-free models that treat cells as point-like particles or extended shapes. However, it remains unclear how these approaches compare when applied to the same biological problem, and what differences in behaviour are due to different model assumptions and abstractions. Here, we exploit the availability of an implementation of five popular cell-based modelling approaches within a consistent computational framework, Chaste (http://www.cs.ox.ac.uk/chaste). This framework allows one to easily change constitutive assumptions within these models. In each case we provide full details of all technical aspects of our model implementations. We compare model implementations using four case studies, chosen to reflect the key cellular processes of proliferation, adhesion, and short- and long-range signalling. These case studies demonstrate the applicability of each model and provide a guide for model usage