An Interdisciplinary Perspective on Artificial Immune Systems
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Recombination and the Evolution of Mutational Robustness
ARTICLE IN PRESS Journal of Theoretical Biology 241 (2006) 707–715 www.elsevier.com/locate/yjtbi Recombination and the evolution of mutational robustness Andy Gardnera,b,c,Ã, Alex T. Kalinkaa aInstitute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK bDepartment of Mathematics & Statistics, Queen’s University, Kingston, Ont., Canada K7L 3N6 cDepartment of Biology, Queen’s University, Kingston, Ont., Canada K7L 3N6 Received 25 July 2005; received in revised form 8 December 2005; accepted 5 January 2006 Available online 20 February 2006 Abstract Mutational robustness is the degree to which a phenotype, such as fitness, is resistant to mutational perturbations. Since most of these perturbations will tend to reduce fitness, robustness provides an immediate benefit for the mutated individual. However, robust systems decay due to the accumulation of deleterious mutations that would otherwise have been cleared by selection. This decay has received very little theoretical attention. At equilibrium, a population or asexual lineage is expected to have a mutation load that is invariant with respect to the selection coefficient of deleterious alleles, so the benefit of robustness (at the level of the population or asexual lineage) is temporary. However, previous work has shown that robustness can be favoured when robustness loci segregate independently of the mutating loci they act upon. We examine a simple two-locus model that allows for intermediate rates of recombination and inbreeding to show that increasing the effective recombination rate allows for the evolution of greater mutational robustness. r 2006 Elsevier Ltd. All rights reserved. Keywords: Canalization; Epistasis; Linkage disequilibrium; Multilocus methodology; Mutation–selection balance 1. -
Editorial Computational and Bioinformatics Techniques for Immunology
Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 263189, 2 pages http://dx.doi.org/10.1155/2014/263189 Editorial Computational and Bioinformatics Techniques for Immunology Francesco Pappalardo,1 Vladimir Brusic,2 Filippo Castiglione,3 and Christian Schönbach2 1 Department of Drug Sciences, University of Catania, 95125 Catania, Italy 2School of Science and Technology, Nazarbayev University, Astana 010000, Kazakhstan 3Istituto Applicazioni del Calcolo “M. Picone”, Consiglio Nazionale delle Ricerche, Via dei Taurini 19, 00185 Rome, Italy Correspondence should be addressed to Francesco Pappalardo; [email protected] Received 22 July 2014; Accepted 22 July 2014; Published 31 December 2014 Copyright © 2014 Francesco Pappalardo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Computational immunology and immunological bioinfor- biology spanning different scales: an open challenge”by matics are well-established and rapidly evolving research F. Castiglione et al. fields. Whereas the former aims to develop mathematical Exploring the connections between classical mathemat- and/or computational methods to study the dynamics of ical modeling (at different scales) and bioinformatics pre- cellular and molecular entities during the immune response dictions of omic scope along with specific aspects of the [1–4], the latter targets proposing methods to analyze large immune system in combination with concepts and methods genomic and proteomic immunological-related datasets and like computer simulations, mathematics and statistics for the derive (i.e., predict) new knowledge mainly by statistical discovery, design, and optimization of drugs, vaccines, and inference and machine learning algorithms. -
Antigen-Receptor Degeneracy and Immunological Paradigms Irun R
Molecular Immunology 40 (2004) 993–996 Antigen-receptor degeneracy and immunological paradigms Irun R. Cohen a,∗, Uri Hershberg b, Sorin Solomon c a The Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100 Israel b Interdisciplinary Center for Neuronal Computation, The Hebrew University of Jerusalem, Jerusalem, Israel c The Racah Institute of Physics, The Hebrew University of Jerusalem, Jerusalem, Israel Abstract This paper discusses some consequences of the discovery that antigen receptors are degenerate: Immune specificity, in contrast to the tenets of the clonal selection paradigm, must be generated by the immune response down-stream of initial antigen recognition; and specificity is a property of a collective of cells and not of single clones. © 2003 Elsevier Ltd. All rights reserved. Keywords: T cells; T-cell receptor; Inflammation; Specificity; Degeneracy; Clonal selection; Cognitive paradigm 1. Degeneracy problems characterized by extreme poly-clonality; in fact, most nat- ural T-cell responses are oligo-clonal (Douek et al., 2003). Degeneracy, in the present discourse, refers to the capac- So, there must be a mechanism or mechanisms that operate ity of any single antigen receptor to bind and respond to to restrict poly-clonality in wild-type adaptive immune sys- (recognize) many different ligands. The Oxford English Dic- tems. The inherent potential for extreme poly-clonality, in tionary (Second Edition, 1989) defines the primary meaning practice, may be tempered by clonal competition. Compe- of degeneracy as: tition among clones for access, energy or space will most likely reward the fast and the avid. Since the best clones Having lost the qualities proper to the race or kind; having should win, clonal competition does not threaten the logic declined from a higher to a lower type; hence, declined of the clonal selection theory (CST) of adaptive immunity. -
Multiple Receptor Tyrosine Kinases Are Expressed in Adult Rat Retinal Ganglion Cells As Revealed by Single-Cell Degenerate Primer Polymerase Chain Reaction
Upsala Journal of Medical Sciences. 2010; 115: 65–80 ORIGINAL ARTICLE Multiple receptor tyrosine kinases are expressed in adult rat retinal ganglion cells as revealed by single-cell degenerate primer polymerase chain reaction NICLAS LINDQVIST1, ULRIKA LÖNNGREN1, MARTA AGUDO2,3, ULLA NÄPÄNKANGAS1, MANUEL VIDAL-SANZ2 & FINN HALLBÖÖK1 1Department of Neuroscience, Unit for Developmental Neuroscience, Biomedical Center, Uppsala University, 75123 Uppsala, Sweden, 2Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain, and 3Fundación para la Formación e Investigación Sanitaria de la Región de Murcia, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain Abstract Background. To achieve a better understanding of the repertoire of receptor tyrosine kinases (RTKs) in adult retinal ganglion cells (RGCs) we performed polymerase chain reaction (PCR), using degenerate primers directed towards conserved sequences in the tyrosine kinase domain, on cDNA from isolated single RGCs univocally identified by retrograde tracing from the superior colliculi. Results. All the PCR-amplified fragments of the expected sizes were sequenced, and 25% of them contained a tyrosine kinase domain. These were: Axl, Csf-1R, Eph A4, Pdgfrb, Ptk7, Ret, Ros, Sky, TrkB, TrkC, Vegfr-2, and Vegfr-3. Non-RTK sequences were Jak1 and 2. Retinal expression of Axl, Csf-1R, Pdgfrb, Ret, Sky, TrkB, TrkC, Vegfr-2, and Vegfr-3, as well as Jak1 and 2, was confirmed by PCR on total retina cDNA. Immunodetection of Csf-1R, Pdgfra/b, Ret, Sky, TrkB, and Vegfr-2 on retrogradely traced retinas demonstrated that they were expressed by RGCs. Co-localization of Vegfr-2 and Csf-1R, of Vegfr-2 and TrkB, and of Csf-1R and Ret in retrogradely labelled RGCs was shown. -
Degeneracy in Hippocampal Physiology and Plasticity
bioRxiv preprint doi: https://doi.org/10.1101/203943; this version posted July 30, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Degeneracy in hippocampal physiology and plasticity * Rahul Kumar Rathour and Rishikesh Narayanan Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India. * Corresponding Author Rishikesh Narayanan, Ph.D. Molecular Biophysics Unit Indian Institute of Science Bangalore 560 012, India. e-mail: [email protected] Phone: +91-80-22933372 Fax: +91-80-23600535 Abbreviated title: Degeneracy in the hippocampus Keywords: hippocampus; degeneracy; learning; memory; encoding; homeostasis; plasticity; physiology; causality; reductionism; holism; structure-function relationships; variability; compensation; intrinsic excitability 1 bioRxiv preprint doi: https://doi.org/10.1101/203943; this version posted July 30, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. ABSTRACT Degeneracy, defined as the ability of structurally disparate elements to perform analogous function, has largely been assessed from the perspective of maintaining robustness of physiology or plasticity. How does the framework of degeneracy assimilate into an encoding system where the ability to change is an essential ingredient for storing new incoming information? Could degeneracy maintain the balance between the apparently contradictory goals of the need to change for encoding and the need to resist change towards maintaining homeostasis? In this review, we explore these fundamental questions with the mammalian hippocampus as an example encoding system. We systematically catalog lines of evidence, spanning multiple scales of analysis, that demonstrate the expression of degeneracy in hippocampal physiology and plasticity. -
Toward Computational Modelling on Immune System Function Francesco Pappalardo1*, Marzio Pennisi2, Pedro A
Pappalardo et al. BMC Bioinformatics 2019, 20(Suppl 6):622 https://doi.org/10.1186/s12859-019-3239-x INTRODUCTION Open Access Toward computational modelling on immune system function Francesco Pappalardo1*, Marzio Pennisi2, Pedro A. Reche3 and Giulia Russo1 From 2nd International Workshop on Computational Methods for the Immune System Function Madrid, Spain. 3–6 December 2018 Abstract The 2nd Computational Methods for the Immune System function Workshop has been held in Madrid in conjunction with the IEEE International Conference on Bioinformatics and Biomedicine (BIBM 2018) in Madrid, Spain, from December 3 to 6, 2018. The workshop has been obtained 100% more submissions in respect to the first edition, highlighting a growing interest for the treated topics. The best papers (9) have been selected for extension in this special issue, with themes about immune system and disease simulation, computer-aided design of novel candidate vaccines, methods for the analysis of immune system involved diseases based on statistical methods, meta-heuristics and game theory, and modelling strategies for improving the simulation of the immune system dynamics. Introduction modeling of the Immune system function, along with their The constant and rapid increasing of computing power application in understanding the pathogenesis of specific has favoured the diffusion of computational methods diseases (e.g., infectious diseases, cancers, hypersensitivi- into immunology, giving the birth to computational ties, autoimmune disorders) has been in our minds for -
Degeneracy and Genetic Assimilation in RNA Evolution Reza Rezazadegan1* and Christian Reidys1,2
Rezazadegan and Reidys BMC Bioinformatics (2018) 19:543 https://doi.org/10.1186/s12859-018-2497-3 RESEARCH ARTICLE Open Access Degeneracy and genetic assimilation in RNA evolution Reza Rezazadegan1* and Christian Reidys1,2 Abstract Background: The neutral theory of Motoo Kimura stipulates that evolution is mostly driven by neutral mutations. However adaptive pressure eventually leads to changes in phenotype that involve non-neutral mutations. The relation between neutrality and adaptation has been studied in the context of RNA before and here we further study transitional mutations in the context of degenerate (plastic) RNA sequences and genetic assimilation. We propose quasineutral mutations, i.e. mutations which preserve an element of the phenotype set, as minimal mutations and study their properties. We also propose a general probabilistic interpretation of genetic assimilation and specialize it to the Boltzmann ensemble of RNA sequences. Results: We show that degenerate sequences i.e. sequences with more than one structure at the MFE level have the highest evolvability among all sequences and are central to evolutionary innovation. Degenerate sequences also tend to cluster together in the sequence space. The selective pressure in an evolutionary simulation causes the population to move towards regions with more degenerate sequences, i.e. regions at the intersection of different neutral networks, and this causes the number of such sequences to increase well beyond the average percentage of degenerate sequences in the sequence space. We also observe that evolution by quasineutral mutations tends to conserve the number of base pairs in structures and thereby maintains structural integrity even in the presence of pressure to the contrary. -
Tyrosine Kinases
KEVANM SHOKAT MINIREVIEW Tyrosine kinases: modular signaling enzymes with tunable specificities Cytoplasmic tyrosine kinases are composed of modular domains; one (SHl) has catalytic activity, the other two (SH2 and SH3) do not. Kinase specificity is largely determined by the binding preferences of the SH2 domain. Attaching the SHl domain to a new SH2 domain, via protein-protein association or mutation, can thus dramatically change kinase function. Chemistry & Biology August 1995, 2:509-514 Protein kinases are one of the largest protein families identified, This is a result of the overlapping substrate identified to date; over 45 new members are identified specificities of many tyrosine kinases, which makes it each year. It is estimated that up to 4 % of vertebrate pro- difficult to dissect the individual signaling pathways by teins are protein kinases [l].The protein kinases are cate- scanning for unique target motifs [2]. gorized by their specificity for serineithreonine, tyrosine, or histidine residues. Protein tyrosine kinases account for The apparent promiscuity of individual tyrosine kinases roughly half of all kinases. They occur as membrane- is a result of their unique structural organization. bound receptors or cytoplasmic proteins and are involved Enzyme specificity is typically programmed by one in a wide variety of cellular functions, including cytokine binding site, which recognizes the substrate and also con- responses, antigen-dependent immune responses, cellular tains exquisitely oriented active-site functional groups transformation by RNA viruses, oncogenesis, regulation that help to lower the energy of the transition state for of the cell cycle, and modification of cell morphology the conversion of specific substrates to products.Tyrosine (Fig. -
Computational Immunology Workshop
Computational Immunology Workshop On the 16th of November, with the support of the Pole Rabelais, the SIRIC Montpellier Cancer, and the IRCM, we organize a 1-day workshop on the theme Computational Immunology. The meeting will take place at IRCM auditorium. We will discuss computational or bioinformatics aspects of immunology and the cancer microenvironment. Recent developments in DNA sequencing and functional proteomics have made possible remarkably successful data driven research in these fields. It requires bioinformatics and computational abilities to transform data into information. The workshop is a unique opportunity to learn from experts who applied such techniques to conduct meaningful biological and translational research. We will welcome prestigious international and French speakers: • Dr Andreas Pichlmair, Max Plank Institute, Munich, innate immunity ; • Dr Fatima Mechta-Grigoriou, Institut Curie, Paris, tumor microenvironment ; • Pr Zlatko Trajanoski, Biocenter, Innsbruck, oncoimmunology ; • Dr Monsef Benkirane, IGH, Montpellier, immunology ; • Pr Marie-Paule Lefranc, IGH, Montpellier, immunoinformatics. Registration is free but mandatory: Inscription In addition, YOU are invited to submit an abstract for an oral or poster presentation (send to [email protected]) and contribute to the success of this workshop. The organizers: Ula Hibner (IGMM), Sofia Kossida (IGH), Jacques Colinge (IRCM). Preliminary Program 08:45 Registration 09:00 Opening and introductory remarks Session 1 Innate and adaptive immunity 09:00 Keynote -
How Do We Evaluate Artificial Immune Systems?
How Do We Evaluate Artificial Immune Systems? Simon M. Garrett [email protected] Computational Biology Group, Department of Computer Science, University of Wales, Aberystwyth, Wales, SY23 3DB. UK Abstract The field of Artificial Immune Systems (AIS) concerns the study and development of computationally interesting abstractions of the immune system. This survey tracks the development of AIS since its inception, and then attempts to make an assessment of its usefulness, defined in terms of ‘distinctiveness’ and ‘effectiveness.’ In this paper, the standard types of AIS are examined—Negative Selection, Clonal Selection and Im- mune Networks—as well as a new breed of AIS, based on the immunological ‘danger theory.’ The paper concludes that all types of AIS largely satisfy the criteria outlined for being useful, but only two types of AIS satisfy both criteria with any certainty. Keywords Artificial immune systems, critical evaluation, negative selection, clonal selection, im- mune network models, danger theory. 1 Introduction What is an artificial immune system (AIS)? One answer is that an AIS is a model of the immune system that can be used by immunologists for explanation, experimentation and prediction activities that would be difficult or impossible in ‘wet-lab’ experiments. This is also known as ‘computational immunology.’ Another answer is that an AIS is an abstraction of one or more immunological processes. Since these processes protect us on a daily basis, from the ever-changing onslaught of biological and biochemical entities that seek to prosper at our expense, it is reasoned that they may be computa- tionally useful. It is this form of AIS—methods based on immune abstractions—that will be studied here. -
Quantitative Immunology for Physicists
bioRxiv preprint doi: https://doi.org/10.1101/696567; this version posted July 28, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Quantitative Immunology for Physicists Gr´egoireAltan-Bonnet,1, ∗ Thierry Mora,2, ∗ and Aleksandra M. Walczak2, ∗ 1Immunodynamics Section, Cancer & Inflammation Program, National Cancer Institute, Bethesda MD 20892, USA 2Laboratoire de physique de l'Ecole´ normale sup´erieure (PSL University), CNRS, Sorbonne Universit´e,Universit´ede Paris, 75005 Paris, France Abstract. The adaptive immune system is a dynamical, self-organized multiscale system that protects vertebrates from both pathogens and internal irregularities, such as tumours. For these reason it fascinates physicists, yet the multitude of different cells, molecules and sub-systems is often also petrifying. Despite this complexity, as experiments on different scales of the adaptive immune system become more quantitative, many physicists have made both theoretical and experimental contributions that help predict the behaviour of ensembles of cells and molecules that participate in an immune response. Here we review some recent contributions with an emphasis on quantitative questions and methodologies. We also provide a more general methods section that presents some of the wide array of theoretical tools used in the field. CONTENTS A. Cytokine signaling and the JAK-STAT pathway 14 I. Introduction 2 1. Cytokine binding and signaling at equilibrium 15 II. Physical chemistry of ligand-receptor 2. Tunability of cytokine responses. 15 interaction: specificity, sensitivity, kinetics. 4 3. Regulation by cytokine consumption 17 A. Diffusion-limited reaction rates 4 4. -
A Numerical Representation and Classification of Codons To
bioRxiv preprint doi: https://doi.org/10.1101/2020.03.02.971036; this version posted March 3, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. A Numerical Representation and Classication of Codons to Investigate Codon Alternation Patterns during Genetic Mutations on Disease Pathogenesis Antara Senguptaa, Pabitra Pal Choudhuryd, Subhadip Chakrabortyb,e, Swarup Royc,∗∗, Jayanta Kumar Dasd,∗, Ditipriya Mallicke, Siddhartha S Janae aDepartment of Master of Computer Applications, MCKV Institute of Engineering, Liluah, India bDepartment of Botany, Nabadwip Vidyasagar College, Nabadwip, India cDepartment of Computer Applications,Sikkim University, Gangtok, Sikkim, India dApplied Statistical Unit, Indian Statistical Institute, Kolkata, India eSchool of Biological Sciences, Indian Association for the Cultivation of Science, Kolkata, India 1. Introduction Genes are the functional units of heredity [4]. It is mainly responsible for the structural and functional changes and for the variation in organisms which could be good or bad. DNA (Deoxyribose Nucleic Acid) sequences build the genes of organisms which in turn encode for particular protein us- ing codon. Any uctuation in this sequence (codons), for example, mishaps during DNA transcription, might lead to a change in the genetic code which alter the protein synthesis. This change is called mutation. Mutation diers from Single Nucleotide Polymorphism(SNP) in many ways [23]. For instance, occurrence of mutation in a population should be less than 1% whereas SNP occurs with greater than 1%. Mutation always occurs in diseased group whereas SNP is occurs in both diseased and control population. Mutation is responsible for some disease phenotype but SNP may or may not be as- sociated with disease phenotype.