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  • articleNo Access

    LOVE KILLS: SIMULATIONS IN PENNA AGEING MODEL

    The standard Penna ageing model with sexual reproduction is enlarged by adding additional bit-strings for love: Marriage happens only if the male love strings are sufficiently different from the female ones. We simulate at what level of required difference the population dies out.

  • chapterOpen Access

    Computational KIR copy number discovery reveals interaction between inhibitory receptor burden and survival

    Natural killer (NK) cells have increasingly become a target of interest for immunotherapies. NK cells express killer immunoglobulin-like receptors (KIRs), which play a vital role in immune response to tumors by detecting cellular abnormalities. The genomic region encoding the 16 KIR genes displays high polymorphic variability in human populations, making it difficult to resolve individual genotypes based on next generation sequencing data. As a result, the impact of polymorphic KIR variation on cancer phenotypes has been understudied. Currently, labor-intensive, experimental techniques are used to determine an individual’s KIR gene copy number profile. Here, we develop an algorithm to determine the germline copy number of KIR genes from whole exome sequencing data and apply it to a cohort of nearly 5000 cancer patients. We use a k-mer based approach to capture sequences unique to specific genes, count their occurrences in the set of reads derived from an individual and compare the individual’s k-mer distribution to that of the population. Copy number results demonstrate high concordance with population copy number expectations. Our method reveals that the burden of inhibitory KIR genes is associated with survival in two tumor types, highlighting the potential importance of KIR variation in understanding tumor development and response to immunotherapy.

  • chapterNo Access

    APPLICATION COMPUTATIONAL INTELLIGENCE FOR DEVELOPMENT OF SYNTHETIC PEPTIDE VACCINE FROM HUMAN ADENOVIRUS-5

    Human Adenovirus-5 causes systemic infections leading to be an obligatory step in infection. Peptide fragments of capsid protein can be used to select nonamers for use in rational vaccine design and to increase the understanding of roles of the immune system in infectious diseases. Analysis shows MHC class II binding peptides of capsid protein from Human Adenovirus-5 are important determinant for protection of host form viral infection. In this assay, we used PSSM and SVM algorithms for antigen design and predicted the binding affinity of capsid protein having 951 amino acids, which shows 944 nonamers. Binding ability prediction of antigen peptides to major histocompatibility complex (MHC) class I & II molecules is important in vaccine development from Human Adenovirus-5.

  • chapterNo Access

    MACHINE INTELLIGENT APPROACH FOR MAPPING OF MHC CLASS BINDING NONAMERS

    Functional analysis of the binding ability of Hpv11 e2 tad protein antigen peptides to major histocompatibility complex (MHC) class molecules is important in vaccine development. Antigenic epitopes of Hpv11 e2 tad protein form Human papilloma virus-11 are important determinant for protection of many host form viral infection. We used PSSM and SVM algorithms for antigen design, which represented predicted binders as MHCII-IAb, MHCII-IAd, MHCII-IAg7, and MHCII- RT1.B nonamers from viral Hpv11 e2 tad crystal structure. These peptide nonamers are from a set of aligned peptides known to bind to a given MHC molecule as the predictor of MHC-peptide binding. Analysis shows potential drug targets to identify active sites against diseases.

  • chapterNo Access

    APPLICATION OF DATA MINING FOR DEVELOPMENT OF SYNTHETIC VACCINE FROM SCORPION TOXIN

    Mesobuthus tamulus involved multiple antigenic components to direct and empower the immune system to protect the host from infection. MHC molecules are cell surface proteins, which take active part in host immune reactions and involvement of MHC class in response to almost all antigens and it give effects on specific sites. This theme is implemented in designing subunit and synthetic peptide vaccines. In this study we used data mining for sequence analysis method and is allows potential drug targets to identify active sites, which form antibodies against or spider venom infection. The method integrates prediction of peptide MHC class binding; proteosomal C terminal cleavage, TAP transport efficiency and epitopes are important antigenic determinants against the scorpion venom infections. Keywords- neurotoxin, MHC, data mining, SVM, PSSM, synthetic vaccine

  • chapterNo Access

    EVIDENCE OF BIOMECHANICS-RESPONDING EVOLUTIONARY THEORY BY USING BIOCERAMICS

    Bioceramics01 Oct 1999

    Trilateral research methods are developed by the author integrating morphology, molecular biology (physiology and biochemistry), and molecular genetics of remodeling by means of biomechanics. Through this research method the author develops artificial bone marrow chamber using bioceramics.

    The author discovers through studies on evolution of hemopoiesis that the morphology of an organism can be changed by vicissitudes of inner or outer stimuli of biomechanics, i.e., environmental factors, which act to the organism, and if these vicissitudes of biomechanical stimuli are transmitted to the next generation morphological changes can be transmitted. Through this discovery the use and disuse theory of Lamarck can be explained biomechanically in molecular genetics.

    Experimental evolutionary studies are carried out as follows: developing artificial bone marrow biochambers, the author has implanted them into archetype vertebrates as well as mammals, compared them each other, and analyzed them. Developments of hemopoiesis in bone marrow chambers in phylogeny are evident as the action of the gravity in terrestrialization, which is converted into heightening of blood pressure in chondrichthyes. As conclusion use and disuse theory is evidenced in second revolution of vertebrates for the gravity to trigger genetic expression in mesenchymal cells not only producing hemopoiesis conjugated with ossification of the cartilage but inducing major histocompatibility complex (MHC).