Parallel pair-wise interaction for multi-agent immune systems modelling

Agent Based Modelling (ABM), is an approach for modelling dynamic systems and studying complex and emergent behaviour. ABM approach is a very common technique in biological domain due to high demand for a large scale analysis tool to collect and interpret information to solve biological problems. However, simulating large scale cellular level models (i.e. large number of agents/entities) require a high degree of computational power which is achievable through parallel computing methods such as Graphics Processing Units (GPUs). The use of parallel approaches in ABMs is growing rapidly specifically when modelling in continuous space system (particle based). Parallel implementation of particle based simulation within continuum space where agents contain quantities of chemicals/substances is very challenging. Pair-wise interactions are different abstraction to continuous space (particle) models which is commonly used for immune system modelling. This paper describes an approach to parallelising the key component of biological and immune system models (pair-wise interactions) within an ABM model. Our performance results demonstrate the applicability of this method to a broader class of biological systems with the same type of cell interactions and that it can be used as the basis for developing complete immune system models on parallel hardware

Randomly Evolving Idiotypic Networks: Structural Properties and Architecture

We consider a minimalistic dynamic model of the idiotypic network of B-lymphocytes. A network node represents a population of B-lymphocytes of the same specificity (idiotype), which is encoded by a bitstring. The links of the network connect nodes with complementary and nearly complementary bitstrings, allowing for a few mismatches. A node is occupied if a lymphocyte clone of the corresponding idiotype exists, otherwise it is empty. There is a continuous influx of new B-lymphocytes of random idiotype from the bone marrow. B-lymphocytes are stimulated by cross-linking their receptors with complementary structures. If there are too many complementary structures, steric hindrance prevents cross-linking. Stimulated cells proliferate and secrete antibodies of the same idiotype as their receptors, unstimulated lymphocytes die. Depending on few parameters, the autonomous system evolves randomly towards patterns of highly organized architecture, where the nodes can be classified into groups according to their statistical properties. We observe and describe analytically the building principles of these patterns, which allow to calculate number and size of the node groups and the number of links between them. The architecture of all patterns observed so far in simulations can be explained this way. A tool for real-time pattern identification is proposed.Comment: 19 pages, 15 figures, 4 table

PI-FLAME: A parallel immune system simulator using the FLAME graphic processing unit environment

Agent-based models (ABMs) are increasingly being used to study population dynamics in complex systems, such as the human immune system. Previously, Folcik et al. (The basic immune simulator: an agent-based model to study the interactions between innate and adaptive immunity. Theor Biol Med Model 2007; 4: 39) developed a Basic Immune Simulator (BIS) and implemented it using the Recursive Porous Agent Simulation Toolkit (RePast) ABM simulation framework. However, frameworks such as RePast are designed to execute serially on central processing units and therefore cannot efficiently handle large model sizes. In this paper, we report on our implementation of the BIS using FLAME GPU, a parallel computing ABM simulator designed to execute on graphics processing units. To benchmark our implementation, we simulate the response of the immune system to a viral infection of generic tissue cells. We compared our results with those obtained from the original RePast implementation for statistical accuracy. We observe that our implementation has a 13× performance advantage over the original RePast implementation

Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates

The management of infectious diseases has become more critical due to the development of novel pathogenic strains with enhanced resistance. Prevotella melaninogenica, a gram-negative bacterium, was found to be involved in various infections of the respiratory tract, aerodigestive tract, and gastrointestinal tract. The need to explore novel drug and vaccine targets against this pathogen was triggered by the emergence of antimicrobial resistance against reported antibiotics to combat P. melaninogenica infections. The study involves core genes acquired from 14 complete P. melaninogenica strain genome sequences, where promiscuous drug and vaccine candidates were explored by state-of-the-art subtractive proteomics and reverse vaccinology approaches. A stringent bioinformatics analysis enlisted 18 targets as novel, essential, and non-homologous to humans and having druggability potential. Moreover, the extracellular and outer membrane proteins were subjected to antigenicity, allergenicity, and physicochemical analysis for the identification of the candidate proteins to design multi-epitope vaccines. Two candidate proteins (ADK95685.1 and ADK97014.1) were selected as the best target for the designing of a vaccine construct. Lead B- and T-cell overlapped epitopes were joined to generate potential chimeric vaccine constructs in combination with adjuvants and linkers. Finally, a prioritized vaccine construct was found to have stable interactions with the human immune cell receptors as confirmed by molecular docking and MD simulation studies. The vaccine construct was found to have cloning and expression ability in the bacterial cloning system. Immune simulation ensured the elicitation of significant immune responses against the designed vaccine. In conclusion, our study reported novel drug and vaccine targets and designed a multi-epitope vaccine against the P. melaninogenica infection. Further experimental validation will help open new avenues in the treatment of this multi-drug-resistant pathogen

Targeting alternative splicing in cancer immunotherapy

Tumor immunotherapy has made great progress in cancer treatment but still faces several challenges, such as a limited number of targetable antigens and varying responses among patients. Alternative splicing (AS) is an essential process for the maturation of nearly all mammalian mRNAs. Recent studies show that AS contributes to expanding cancer-specific antigens and modulating immunogenicity, making it a promising solution to the above challenges. The organoid technology preserves the individual immune microenvironment and reduces the time/economic costs of the experiment model, facilitating the development of splicing-based immunotherapy. Here, we summarize three critical roles of AS in immunotherapy: resources for generating neoantigens, targets for immune-therapeutic modulation, and biomarkers to guide immunotherapy options. Subsequently, we highlight the benefits of adopting organoids to develop AS-based immunotherapies. Finally, we discuss the current challenges in studying AS-based immunotherapy in terms of existing bioinformatics algorithms and biological technologies

Emergent networks in immune system shape space

The development of a computational model is reported which facilitates the study of emergent principles of human immune system effector T cell clonotype repertoire and its distribution and differentiation. In particular, the question of systemic self-organisation is addressed. The model represents an extension to earlier immune system shape space formalism, such that each activated effector T cell clonotype and respective immunogenic viral epitope is represented as a node in a two-dimensional network space, and edges between nodes models the affinity and clearance pressure applied to the antigen presenting cell bearing the target epitope. As the model is repeatedly exposed to infection by heterologous or mutating viruses, a distinct topology of the network shape space emerges which may offer a theoretical explanation of recent biological experimental results in the field of murine (mouse) cytotoxic T cell activation, apoptosis, crossreactivity, and memory - especially with respect to repeated reinfection. In the past, most discrete computational models of immune response to vira l infections have used separate real space or shape space formalisms. In this work, however, we have developed a model based on a combination of the two, with the objective of demonstrating how emergent behaviour and principles of self organisation may arise from a many-particle microscopic system. This is achieved by using a stochastic model of the lymphatic system as stimulus to a networ