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Immunome Research

Paul Zarogoulidis, Lonny Yarmus, Kaid Darwiche, Robert Walter, Haidong Huang, Zhigang Li, Bojan Zaric, Kosmas Tsakiridis, Konstantinos Zarogoulidis
Interleukin 6 is a multifunctional cytokine. Its increased levels have been associated with elevated cancer risk, and also these levels have been found to be a prognostic factor for several cancer types. In addition, increased levels have been found in coronary heart disease, insulin resistant patients, advance stage cancer patients, atopy/asthma and in patients with blood circulating micrometastasis. Additionally several studies with different types of cancers have been performed to identify the correlation between interleukin-6 levels, stage, treatment response and severity of symptoms...
August 12, 2013: Immunome Research
Kerrie Vaughan, Bjoern Peters, Roberto Mallone, Matthias von Herrath, Bart O Roep, Alessandro Sette
BACKGROUND: The Immune Epitope Database (IEDB), originally focused on infectious diseases, was recently expanded to allergy, transplantation and autoimmunity diseases. Here we focus on diabetes, chosen as a prototype autoimmune disease. We utilize a combined tutorial and meta-analysis format, which demonstrates how common questions, related to diabetes epitopes can be answered. RESULTS: A total of 409 references are captured in the IEDB describing >2,500 epitopes from diabetes associated antigens...
2013: Immunome Research
Kerrie Vaughan, Bjoern Peters, Roberto Mallone, Matthias von Herrath, Bart O Roep, Alessandro Sette
Background: The Immune Epitope Database (IEDB), originally focused on infectious diseases, was recently expanded to allergy, transplantation and autoimmunity diseases. Here we focus on diabetes, chosen as a prototype autoimmune disease. We utilize a combined tutorial and meta-analysis format, which demonstrates how common questions, related to diabetes epitopes can be answered. Results: A total of 409 references are captured in the IEDB describing >2,500 epitopes from diabetes associated antigens. The vast majority of data were derived from GAD, insulin, IA-2/PTPRN, IGRP, ZnT8, HSP, and ICA-1, and the experiments related to T cell epitopes and MHC binding far outnumbers B cell assays...
2013: Immunome Research
Anne S De Groot, Matthew Ardito, Leonard Moise, Eric A Gustafson, Denice Spero, Gloria Tejada, William Martin
BACKGROUND: Biodefense vaccines against Category B bioterror agents Burkholderia pseudomallei (BPM) and Burkholderia mallei (BM) are needed, as they are both easily accessible to terrorists and have strong weaponization potential. Burkholderia cepaciae (BC), a related pathogen, causes chronic lung infections in cystic fibrosis patients. Since BPM, BM and BC are all intracellular bacteria, they are excellent targets for T cell-based vaccines. However, the sheer volume of available genomic data requires the aid of immunoinformatics for vaccine design...
May 2011: Immunome Research
Timothy J Messitt, Frances Terry, Leonard Moise, William Martin, Anne S De Groot
BACKGROUND: Methods for identifying physiologically relevant T-cell epitopes are critically important for development of vaccines and the design of therapeutic proteins. As the number of proteins that are being evaluated for putative immunogenicity expands, rapid and accurate tools are in great demand. Several methods to identify T-cell epitopes have been developed, the most recent of which is a cell free system consisting of a minimal set of proteases incubated with HLA DRB1*0101, HLA-DM and whole antigen...
May 2011: Immunome Research
Lars Rønn Olsen, Guang Lan Zhang, Ellis L Reinherz, Vladimir Brusic
BACKGROUND: The flavivirus genus is unusually large, comprising more than 70 species, of which more than half are known human pathogens. It includes a set of clinically relevant infectious agents such as dengue, West Nile, yellow fever, and Japanese encephalitis viruses. Although these pathogens have been studied extensively, safe and efficient vaccines lack for the majority of the flaviviruses. RESULTS: We have assembled a database that combines antigenic data of flaviviruses, specialized analysis tools, and workflows for automated complex analyses focusing on applications in immunology and vaccinology...
2011: Immunome Research
Michael T Zimmermann, Aris Skliros, Andrzej Kloczkowski, Robert L Jernigan
Motions of the IgG structure are evaluated using normal mode analysis of an elastic network model to detect hinges, the dominance of low frequency modes, and the most important internal motions. One question we seek to answer is whether or not IgG hinge motions facilitate antigen binding. We also evaluate the protein crystal and packing effects on the experimental temperature factors and disorder predictions. We find that the effects of the protein environment on the crystallographic temperature factors may be misleading for evaluating specific functional motions of IgG...
2011: Immunome Research
Matthew Ardito, Joanna Fueyo, Ryan Tassone, Frances Terry, Kristen DaSilva, Songhua Zhang, William Martin, Anne S De Groot, Steven F Moss, Leonard Moise
BACKGROUND: One useful application of pattern matching algorithms is identification of major histocompatability complex (MHC) ligands and T-cell epitopes. Peptides that bind to MHC molecules and interact with T cell receptors to stimulate the immune system are critical antigens for protection against infectious pathogens. We describe a genomes-to-vaccine approach to H. pylori vaccine design that takes advantage of immunoinformatics algorithms to rapidly identify T-cell epitope sequences from large genomic datasets...
2011: Immunome Research
Chen Yanover, Effie W Petersdorf, Mari Malkki, Ted Gooley, Stephen Spellman, Andrea Velardi, Peter Bardy, Alejandro Madrigal, Jean-Denis Bignon, Philip Bradley
The success of hematopoietic cell transplantation from an unrelated donor depends in part on the degree of Human Histocompatibility Leukocyte Antigen (HLA) matching between donor and patient. We present a structure-based analysis of HLA mismatching, focusing on individual amino acid mismatches and their effect on peptide binding specificity. Using molecular modeling simulations of HLA-peptide interactions, we find evidence that amino acid mismatches predicted to perturb peptide binding specificity are associated with higher risk of mortality in a large and diverse dataset of patient-donor pairs assembled by the International Histocompatibility Working Group in Hematopoietic Cell Transplantation consortium...
2011: Immunome Research
Michal Barak, Guy Eilat, Ron Unger, Ramit Mehr
BACKGROUND: The extraordinary diversity characterizing the antibody repertoire is generated by both evolution and lymphocyte development. Much of this diversity is due to the existence of immunoglobulin (Ig) variable region gene segment libraries, which were diversified during evolution and, in higher vertebrates, are used in generating the combinatorial diversity of antibody genes. The aim of the present study was to address the following questions: What evolutionary parameters affect the size and structure of gene libraries? Are the number of genes in libraries of contemporary species, and the corresponding gene locus structure, a random result of evolutionary history, or have these properties been optimized with respect to individual or population fitness? If a larger number of genes or different genome structures do not increase the fitness, then the current structure is probably optimized...
2010: Immunome Research
Hua Cong, Ernest J Mui, William H Witola, John Sidney, Jeff Alexander, Alessandro Sette, Ajesh Maewal, Rima McLeod
BACKGROUND: Toxoplasmosis causes loss of life, cognitive and motor function, and sight. A vaccine is greatly needed to prevent this disease. The purpose of this study was to use an immmunosense approach to develop a foundation for development of vaccines to protect humans with the HLA-A03 supertype. Three peptides had been identified with high binding scores for HLA-A03 supertypes using bioinformatic algorhythms, high measured binding affinity for HLA-A03 supertype molecules, and ability to elicit IFN-γ production by human HLA-A03 supertype peripheral blood CD8+ T cells from seropositive but not seronegative persons...
2010: Immunome Research
Robert J Milewski, Yutaro Kumagai, Katsumasa Fujita, Daron M Standley, Nicholas I Smith
BACKGROUND: Macrophages represent the front lines of our immune system; they recognize and engulf pathogens or foreign particles thus initiating the immune response. Imaging macrophages presents unique challenges, as most optical techniques require labeling or staining of the cellular compartments in order to resolve organelles, and such stains or labels have the potential to perturb the cell, particularly in cases where incomplete information exists regarding the precise cellular reaction under observation...
2010: Immunome Research
Duccio Cavalieri, Damariz Rivero, Luca Beltrame, Sonja I Buschow, Enrica Calura, Lisa Rizzetto, Sandra Gessani, Maria C Gauzzi, Walter Reith, Andreas Baur, Roberto Bonaiuti, Marco Brandizi, Carlotta De Filippo, Ugo D'Oro, Sorin Draghici, Isabelle Dunand-Sauthier, Evelina Gatti, Francesca Granucci, Michaela Gündel, Matthijs Kramer, Mirela Kuka, Arpad Lanyi, Cornelis Jm Melief, Nadine van Montfoort, Renato Ostuni, Philippe Pierre, Razvan Popovici, Eva Rajnavolgyi, Stephan Schierer, Gerold Schuler, Vassili Soumelis, Andrea Splendiani, Irene Stefanini, Maria G Torcia, Ivan Zanoni, Raphael Zollinger, Carl G Figdor, Jonathan M Austyn
BACKGROUND: The advent of Systems Biology has been accompanied by the blooming of pathway databases. Currently pathways are defined generically with respect to the organ or cell type where a reaction takes place. The cell type specificity of the reactions is the foundation of immunological research, and capturing this specificity is of paramount importance when using pathway-based analyses to decipher complex immunological datasets. Here, we present DC-ATLAS, a novel and versatile resource for the interpretation of high-throughput data generated perturbing the signaling network of dendritic cells (DCs)...
2010: Immunome Research
Morten Nielsen, Sune Justesen, Ole Lund, Claus Lundegaard, Søren Buus
BACKGROUND: Binding of peptides to Major Histocompatibility class II (MHC-II) molecules play a central role in governing responses of the adaptive immune system. MHC-II molecules sample peptides from the extracellular space allowing the immune system to detect the presence of foreign microbes from this compartment. Predicting which peptides bind to an MHC-II molecule is therefore of pivotal importance for understanding the immune response and its effect on host-pathogen interactions. The experimental cost associated with characterizing the binding motif of an MHC-II molecule is significant and large efforts have therefore been placed in developing accurate computer methods capable of predicting this binding event...
2010: Immunome Research
Johannes Söllner, Andreas Heinzel, Georg Summer, Raul Fechete, Laszlo Stipkovits, Susan Szathmary, Bernd Mayer
BACKGROUND: The last years have seen a renaissance of the vaccine area, driven by clinical needs in infectious diseases but also chronic diseases such as cancer and autoimmune disorders. Equally important are technological improvements involving nano-scale delivery platforms as well as third generation adjuvants. In parallel immunoinformatics routines have reached essential maturity for supporting central aspects in vaccinology going beyond prediction of antigenic determinants. On this basis computational vaccinology has emerged as a discipline aimed at ab-initio rational vaccine design...
2010: Immunome Research
Galina F Denisova, Dimitri A Denisov, Jonathan L Bramson
To properly characterize protective polyclonal antibody responses, it is necessary to examine epitope specificity. Most antibody epitopes are conformational in nature and, thus, cannot be identified using synthetic linear peptides. Cyclic peptides can function as mimetics of conformational epitopes (termed mimotopes), thereby providing targets, which can be selected by immunoaffinity purification. However, the management of large collections of random cyclic peptides is cumbersome. Filamentous bacteriophage provides a useful scaffold for the expression of random peptides (termed phage display) facilitating both the production and manipulation of complex peptide libraries...
2010: Immunome Research
Samuel Ojosnegros, Niko Beerenwinkel
Viruses are fast evolving pathogens that continuously adapt to the highly variable environments they live and reproduce in. Strategies devoted to inhibit virus replication and to control their spread among hosts need to cope with these extremely heterogeneous populations and with their potential to avoid medical interventions. Computational techniques such as phylogenetic methods have broadened our picture of viral evolution both in time and space, and mathematical modeling has contributed substantially to our progress in unraveling the dynamics of virus replication, fitness, and virulence...
2010: Immunome Research
Darren R Flower, Kanchan Phadwal, Isabel K Macdonald, Peter V Coveney, Matthew N Davies, Shunzhou Wan
Atomistic Molecular Dynamics provides powerful and flexible tools for the prediction and analysis of molecular and macromolecular systems. Specifically, it provides a means by which we can measure theoretically that which cannot be measured experimentally: the dynamic time-evolution of complex systems comprising atoms and molecules. It is particularly suitable for the simulation and analysis of the otherwise inaccessible details of MHC-peptide interaction and, on a larger scale, the simulation of the immune synapse...
2010: Immunome Research
Claus Lundegaard, Ilka Hoof, Ole Lund, Morten Nielsen
Sequence based T-cell epitope predictions have improved immensely in the last decade. From predictions of peptide binding to major histocompatibility complex molecules with moderate accuracy, limited allele coverage, and no good estimates of the other events in the antigen-processing pathway, the field has evolved significantly. Methods have now been developed that produce highly accurate binding predictions for many alleles and integrate both proteasomal cleavage and transport events. Moreover have so-called pan-specific methods been developed, which allow for prediction of peptide binding to MHC alleles characterized by limited or no peptide binding data...
2010: Immunome Research
Yasser El-Manzalawy, Vasant Honavar
Identification of epitopes that invoke strong responses from B-cells is one of the key steps in designing effective vaccines against pathogens. Because experimental determination of epitopes is expensive in terms of cost, time, and effort involved, there is an urgent need for computational methods for reliable identification of B-cell epitopes. Although several computational tools for predicting B-cell epitopes have become available in recent years, the predictive performance of existing tools remains far from ideal...
2010: Immunome Research
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