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Repertoire Bioinformatics Immune

Lauren E Higdon, Steven Schaffert, Purvesh Khatri, Jonathan S Maltzman
Recently developed single-cell profiling technologies hold promise to provide new insights including analysis of population heterogeneity and linkage of antigen receptors with gene expression. These technologies produce complex data sets that require knowledge of bioinformatics for appropriate analysis. In this minireview, we discuss several single-cell immune profiling technologies for gene and protein expression, including cytometry by time-of-flight, RNA sequencing, and antigen receptor sequencing, as well as key considerations for analysis that apply to each...
February 15, 2019: American Journal of Transplantation
Véronique Adoue, Bénédicte Binet, Agathe Malbec, Joanna Fourquet, Paola Romagnoli, Joost P M van Meerwijk, Sebastian Amigorena, Olivier P Joffre
Upon activation, naive CD4+ T cells differentiate into distinct T cell subsets via processes reliant on epigenetically regulated, lineage-specific developmental programs. Here, we examined the function of the histone methyltransferase SETDB1 in T helper (Th) cell differentiation. Setdb1-/- naive CD4+ T cells exhibited exacerbated Th1 priming, and when exposed to a Th1-instructive signal, Setdb1-/- Th2 cells crossed lineage boundaries and acquired a Th1 phenotype. SETDB1 did not directly control Th1 gene promoter activity but relied instead on deposition of the repressive H3K9me3 mark at a restricted and cell-type-specific set of endogenous retroviruses (ERVs) located in the vicinity of genes involved in immune processes...
January 31, 2019: Immunity
Wei Zhang, Xinyue Li, Longlong Wang, Jianxiang Deng, Liya Lin, Lei Tian, Jinghua Wu, Chenling Tang, Huanming Yang, Jian Wang, Ping Qiu, Tong-Ming Fu, Nitin K Saksena, I-Ming Wang, Xiao Liu
The rhesus macaque is a valuable preclinical animal model to estimate vaccine effectiveness and is also important for understanding Ab maturation and B cell repertoire evolution responding to vaccination. However, incomplete mapping of rhesus Ig germline genes hinders the research efforts. To address this deficiency, we sequenced the BCR repertoires of 75 Indian rhesus macaques. Using a bioinformatic method that has been validated with BCR repertoire analysis of three human donors, we were able to infer rhesus variable (V) and joint (J) germline alleles...
January 30, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Zachary Sethna, Yuval Elhanati, Curtis G Callan, Aleksandra M Walczak, Thierry Mora
Motivation: High-throughput sequencing of large immune repertoires has enabled the development of methods to predict the probability of generation by V(D)J recombination of T- and B-cell receptors of any specific nucleotide sequence. These generation probabilities are very non-homogeneous, ranging over 20 orders of magnitude in real repertoires. Since the function of a receptor really depends on its protein sequence, it is important to be able to predict this probability of generation at the amino acid level...
January 18, 2019: Bioinformatics
Zhixiong Zhong, Heming Wu, Qifeng Zhang, Wei Zhong, Pingsen Zhao
BACKGROUND: T cells are key regulators of immunity and one of the cells recruited in atherosclerosis and participated in various stages of the development of atherosclerosis. Characterizing T-cell receptor (TCR) repertoires is a priority of great scientific interest and potential clinical utility for the early diagnosis, risk stratification and prognostic evaluation of acute myocardial infarction (AMI). METHODS: The TCR repertoires in 21 subjects including 7 patients with non-ST-segment elevation myocardial infarction (NSTEMI), 6 patients with ST-segment elevation myocardial infarction (STEMI) and 8 subjects with normal coronary artery (NCA) as control were characterized by using high-throughput sequencing...
January 11, 2019: Journal of Translational Medicine
Vincent Maibach, Linda Vigilant
BACKGROUND: The highly polymorphic genes of the major histocompatibility complex (MHC) class I are involved in defense against viruses and other intracellular pathogens. Although several studies found reduced MHC class I diversity in bonobos in comparison to the closely related chimpanzee, it is unclear if this lower diversity also influences the functional ability of MHC class I molecules in bonobos. Here, we use a bioinformatic approach to analyze the viral peptide binding ability of all published bonobo MHC class I molecules (n = 58) in comparison to all published chimpanzee MHC class I molecules (n = 161) for the class I loci A, B, C and A-like...
January 10, 2019: BMC Evolutionary Biology
Ronit Rosenfeld, Anat Zvi, Eitan Winter, Ronen Hope, Ofir Israeli, Ohad Mazor, Gur Yaari
Recombinant antibodies serve as therapeutic molecules for a broad range of applications. High affinity antibodies are typically isolated following an active and effective immunization. Human-like antibodies may be obtained from immunized nonhuman primates (NHP), such as rhesus macaque, when immunized human origin is not available. For the isolation of such antibodies, strategies like phage and yeast display, are employed. These strategies are primarily based on the amplification of the rearranged variable (V) regions coded by mRNA, obtained from lymphatic source of immunized animals...
November 22, 2018: Journal of Immunological Methods
M Pinto, A González-Díaz, M P Machado, S Duarte, L Vieira, J A Carriço, S Marti, M P Bajanca-Lavado, J P Gomes
The human-restricted bacterium Haemophilus influenzae is responsible for respiratory infections in both children and adults. While colonization begins in the upper airways, it can spread throughout the respiratory tract potentially leading to invasive infections. Although the spread of H. influenzae serotype b (Hib) has been prevented by vaccination, the emergence of infections by other serotypes as well as by non-typeable isolates (NTHi) have been observed, prompting the need for novel prevention strategies...
October 31, 2018: Infection, Genetics and Evolution
Melissah Rowe, Sheri Skerget, Matthew A Rosenow, Timothy L Karr
Spermatozoa exhibit remarkable variability in size, shape, and performance. Our understanding of the molecular basis of this variation, however, is limited, especially in avian taxa. The zebra finch (Taeniopygia guttata) is a model organism in the study of avian sperm biology and sperm competition. Using LC-MS based proteomics, we identify and describe 494 proteins of the zebra finch sperm proteome (ZfSP). Gene ontology and associated bioinformatics analyses revealed a rich repertoire of proteins essential to sperm structure and function, including proteins linked to metabolism and energetics, as well as tubulin binding and microtubule related functions...
October 23, 2018: Journal of Proteomics
Alexander Dimitri Yermanos, Andreas Kevin Dounas, Tanja Stadler, Annette Oxenius, Sai T Reddy
Antibody evolution studies have been traditionally limited to either tracing a single clonal lineage (B cells derived from a single V-(D)-J recombination) over time or examining bulk functionality changes (e.g., tracing serum polyclonal antibody proteins). Studying a single B cell disregards the majority of the humoral immune response, whereas bulk functional studies lack the necessary resolution to analyze the co-existing clonal diversity. Recent advances in high-throughput sequencing (HTS) technologies and bioinformatics have made it possible to examine multiple co-evolving antibody monoclonal lineages within the context of a single repertoire...
2018: Frontiers in Immunology
Pouya Faridi, Chen Li, Sri H Ramarathinam, Julian P Vivian, Patricia T Illing, Nicole A Mifsud, Rochelle Ayala, Jiangning Song, Linden J Gearing, Paul J Hertzog, Nicola Ternette, Jamie Rossjohn, Nathan P Croft, Anthony W Purcell
The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i...
October 12, 2018: Science Immunology
Valerie Odon, Iliana Georgana, Joe Holley, Jordi Morata, Carlos Maluquer de Motes
Ankyrin repeat (ANK) domains are one of the most abundant motifs in eukaryotic proteins. ANK proteins are rare amongst viruses with the exception of poxviruses, which presumably acquired them from the host via horizontal gene transfer. The architecture of poxvirus ANK proteins is however different from their cellular counterparts and this precludes a direct acquisition event. Here we combine bioinformatics analysis and quantitative proteomics to discovera new class of viral ANK proteins with a domain organisation that relates to cellular ANK proteins...
September 26, 2018: Journal of Virology
Patrick V Holec, Joseph Berleant, Mark Bathe, Michael E Birnbaum
Motivation: The study of T cell receptor repertoires has generated new insights into immune system recognition. However, the ability to robustly characterize these populations has been limited by technical barriers and an inability to reliably infer heterodimeric chain pairings for T cell receptors. Results: Here, we describe a novel analytical approach to an emerging immune repertoire sequencing method, improving the resolving power of this low-cost technology...
September 12, 2018: Bioinformatics
Kerry A Ramsbottom, Daniel F Carr, Andrew R Jones, Daniel J Rigden
Adverse drug reactions have been linked with genetic polymorphisms in HLA genes in numerous different studies. HLA proteins have an essential role in the presentation of self and non-self peptides, as part of the adaptive immune response. Amongst the associated drugs-allele combinations, anti-HIV drug Abacavir has been shown to be associated with the HLA-B*57:01 allele, and anti-epilepsy drug Carbamazepine with B*15:02, in both cases likely following the altered peptide repertoire model of interaction. Under this model, the drug binds directly to the antigen presentation region, causing different self peptides to be presented, which trigger an unwanted immune response...
September 2018: Molecular Immunology
Magdalena Migalska, Alvaro Sebastian, Jacek Radwan
In recent years, immune repertoire profiling with high-throughput sequencing (HTS) has advanced our understanding of adaptive immunity. However, fast progress in the field applied mostly to human and mouse research, with only few studies devoted to other model vertebrates. We present the first in-depth characterization of the T-cell receptor (TCR) repertoire in a non-model mammal (bank vole, Myodes glareolus), widely used in ecological and evolutionary research. We used RNA from spleens, 5'RACE and HTS to describe V and J segments of TCRβ, qualitatively characterize preferential V-J segment usage and CDR3 length distribution...
August 2, 2018: Scientific Reports
Emanuele Sasso, Chiara D'Avino, Margherita Passariello, Anna Morena D'Alise, Daniela Siciliano, Maria Luisa Esposito, Guendalina Froechlich, Riccardo Cortese, Elisa Scarselli, Nicola Zambrano, Alfredo Nicosia, Claudia De Lorenzo
Immune checkpoints are emerging as novel targets for cancer therapy, and antibodies against them have shown remarkable clinical efficacy with potential for combination treatments to achieve high therapeutic index. This work aims at providing a novel approach for the generation of several novel human immunomodulatory antibodies capable of binding their targets in their native conformation and useful for therapeutic applications. We performed a massive parallel screening of phage libraries by using for the first time activated human lymphocytes to generate large collections of single-chain variable fragments (scFvs) against 10 different immune checkpoints: LAG-3, PD-L1, PD-1, TIM3, BTLA, TIGIT, OX40, 4-1BB, CD27 and ICOS...
October 2018: MAbs
Serra E Elliott, Sarah Kongpachith, Nithya Lingampalli, Julia Z Adamska, Bryan J Cannon, Rong Mao, Lisa K Blum, William H Robinson
OBJECTIVE: Rheumatoid arthritis (RA) is characterized by the presence of anti-citrullinated protein antibodies (ACPAs); nevertheless, the origin, specificity, and functional properties of ACPAs remain poorly understood. The aim of this study was to characterize the evolution of ACPAs by sequencing the plasmablast antibody repertoire at serial time points in patients with established RA. METHODS: Blood samples were obtained at up to 4 serial time points from 8 individuals with established RA who were positive for ACPAs by the anti-cyclic citrullinated peptide test...
December 2018: Arthritis & Rheumatology
Ludmila Danilova, Valsamo Anagnostou, Justina X Caushi, John-William Sidhom, Haidan Guo, Hok Yee Chan, Prerna Suri, Ada Tam, Jiajia Zhang, Margueritta El Asmar, Kristen A Marrone, Jarushka Naidoo, Julie R Brahmer, Patrick M Forde, Alexander S Baras, Leslie Cope, Victor E Velculescu, Drew M Pardoll, Franck Housseau, Kellie N Smith
Mutation-associated neoantigens (MANA) are a target of antitumor T-cell immunity. Sensitive, simple, and standardized assays are needed to assess the repertoire of functional MANA-specific T cells in oncology. Assays analyzing in vitro cytokine production such as ELISpot and intracellular cytokine staining have been useful but have limited sensitivity in assessing tumor-specific T-cell responses and do not analyze antigen-specific T-cell repertoires. The FEST (Functional Expansion of Specific T cells) assay described herein integrates T-cell receptor sequencing of short-term, peptide-stimulated cultures with a bioinformatic platform to identify antigen-specific clonotypic amplifications...
August 2018: Cancer Immunology Research
Scott Christley, Walter Scarborough, Eddie Salinas, William H Rounds, Inimary T Toby, John M Fonner, Mikhail K Levin, Min Kim, Stephen A Mock, Christopher Jordan, Jared Ostmeyer, Adam Buntzman, Florian Rubelt, Marco L Davila, Nancy L Monson, Richard H Scheuermann, Lindsay G Cowell
Background: Recent technological advances in immune repertoire sequencing have created tremendous potential for advancing our understanding of adaptive immune response dynamics in various states of health and disease. Immune repertoire sequencing produces large, highly complex data sets, however, which require specialized methods and software tools for their effective analysis and interpretation. Results: VDJServer is a cloud-based analysis portal for immune repertoire sequence data that provide access to a suite of tools for a complete analysis workflow, including modules for preprocessing and quality control of sequence reads, V(D)J gene segment assignment, repertoire characterization, and repertoire comparison...
2018: Frontiers in Immunology
Stacey L Wooden, Wayne C Koff
Although the success of vaccination to date has been unprecedented, our inadequate understanding of the details of the human immune response to immunization has resulted in several recent vaccine failures and significant delays in the development of high-need vaccines for global infectious diseases and cancer. Because of the need to better understand the immense complexity of the human immune system, the Human Vaccines Project was launched in 2015 with the mission to decode the human immune response to accelerate development of vaccines and immunotherapies for major diseases...
2018: Human Vaccines & Immunotherapeutics
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