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Repertoire Bioinformatics Immune

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https://www.readbyqxmd.com/read/30072736/profiling-of-the-tcr%C3%AE-repertoire-in-non-model-species-using-high-throughput-sequencing
#1
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
https://www.readbyqxmd.com/read/29995563/massive-parallel-screening-of-phage-libraries-for-the-generation-of-repertoires-of-human-immunomodulatory-monoclonal-antibodies
#2
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...
July 11, 2018: MAbs
https://www.readbyqxmd.com/read/29927104/affinity-maturation-drives-epitope-spreading-and-generation-of-pro-inflammatory-anti-citrullinated-protein-antibodies-in-rheumatoid-arthritis
#3
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 anti-citrullinated protein antibodies (ACPAs), nevertheless, the origin, specificity, and functional properties of ACPAs remain poorly understood. To characterize the evolution of ACPAs, we sequenced the plasmablast antibody repertoire at serial timepoints in subjects with established RA. METHODS: Blood samples were obtained at up to four timepoints from eight anti-CCP+ individuals with established RA. We single-cell sorted CD19+CD3-IgD-CD14-CD20-CD27+CD38++ plasmablasts and co-stained with citrullinated-peptide tetramers to identify ACPA-expressing plasmablasts...
June 21, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29895573/the-mutation-associated-neoantigen-functional-expansion-of-specific-t-cells-manafest-assay-a-sensitive-platform-for-monitoring-antitumor-immunity
#4
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
https://www.readbyqxmd.com/read/29867956/vdjserver-a-cloud-based-analysis-portal-and-data-commons-for-immune-repertoire-sequences-and-rearrangements
#5
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
https://www.readbyqxmd.com/read/29847214/the-human-vaccines-project-towards-a-comprehensive-understanding-of-the-human-immune-response-to-immunization
#6
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...
May 30, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29669518/irprofiler-a-software-toolbox-for-high-throughput-immune-receptor-profiling
#7
Christos Maramis, Athanasios Gkoufas, Anna Vardi, Evangelia Stalika, Kostas Stamatopoulos, Anastasia Hatzidimitriou, Nicos Maglaveras, Ioanna Chouvarda
BACKGROUND: The study of the huge diversity of immune receptors, often referred to as immune repertoire profiling, is a prerequisite for diagnosis, prognostication and monitoring of hematological disorders. In the era of high-throughput sequencing (HTS), the abundance of immunogenetic data has revealed unprecedented opportunities for the thorough profiling of T-cell receptors (TR) and B-cell receptors (BcR). However, the volume of the data to be analyzed mandates for efficient and ease-to-use immune repertoire profiling software applications...
April 18, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29666626/next-generation-immune-repertoire-sequencing-as-a-clue-to-elucidate-the-landscape-of-immune-modulation-by-host-gut-microbiome-interactions
#8
Tatsuo Ichinohe, Takahiko Miyama, Takakazu Kawase, Yasuko Honjo, Kazutaka Kitaura, Hiroyuki Sato, Tadasu Shin-I, Ryuji Suzuki
The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29659703/b-cell-receptor-reconstruction-from-single-cell-rna-seq-with-vdjpuzzle
#9
Simone Rizzetto, David N P Koppstein, Jerome Samir, Mandeep Singh, Joanne H Reed, Curtis H Cai, Andrew R Lloyd, Auda A Eltahla, Christopher C Goodnow, Fabio Luciani
Motivation: The B-cell receptor (BCR) performs essential functions for the adaptive immune system including recognition of pathogen-derived antigens. The vast repertoire and adaptive variation of BCR sequences due to V(D)J recombination and somatic hypermutation (SHM) necessitates single-cell characterization of BCR sequences. Single-cell RNA sequencing (scRNA-seq) presents the opportunity for simultaneous capture of paired BCR heavy and light chains and the transcriptomic signature. Results: We developed VDJPuzzle, a novel bioinformatic tool that reconstructs productive, full-length B-cell receptor sequences of both heavy and light chains and extract somatic mutations on the VDJ region...
April 5, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29650230/production-of-spliced-peptides-by-the-proteasome
#10
Nathalie Vigneron, Vincent Stroobant, Violette Ferrari, Joanna Abi Habib, Benoit J Van den Eynde
CD8+ cytolytic T lymphocytes are essential players of anti-tumor immune responses. On tumors, they recognize peptides of about 8-to-10 amino acids that generally result from the degradation of cellular proteins by the proteasome. Until a decade ago, these peptides were thought to solely correspond to linear fragments of proteins that were liberated after the hydrolysis of the peptide bonds located at their extremities. However, several examples of peptides containing two fragments originally distant in the protein sequence challenged this concept and demonstrated that proteasome could also splice peptides together by creating a new peptide bond between two distant fragments...
April 9, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29568935/integrated-analysis-of-b%C3%A2-cell-and-t%C3%A2-cell-receptors-by-high%C3%A2-throughput-sequencing-reveals-conserved-repertoires-in-iga-nephropathy
#11
Minglin Ou, Fengping Zheng, Xinzhou Zhang, Song Liu, Donge Tang, Peng Zhu, Jingjun Qiu, Yong Dai
Immunoglobulin A nephropathy (IgAN) is a type of glomerular disorder associated with immune dysregulation, and understanding B‑/T‑cell receptors (BCRs/TCRs) may be valuable for the development of specific immunotherapeutic interventions. In the present study, B and T cells were isolated from IgAN patients and healthy controls, and the composition of the BCR/TCR complementarity‑determining region (CDR)3 was analyzed by multiplex polymerase chain reaction, high‑throughput sequencing and bioinformatics...
May 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29563531/virulence-factors-of-moraxella-catarrhalis-outer-membrane-vesicles-are-major-targets-for-cross-reactive-antibodies-and-have-adapted-during-evolution
#12
Daria Augustyniak, Rafał Seredyński, Siobhán McClean, Justyna Roszkowiak, Bartosz Roszniowski, Darren L Smith, Zuzanna Drulis-Kawa, Paweł Mackiewicz
Moraxella catarrhalis is a common human respiratory tract pathogen. Its virulence factors associated with whole bacteria or outer membrane vesicles (OMVs) aid infection, colonization and may induce specific antibodies. To investigate pathogen-host interactions, we applied integrated bioinformatic and immunoproteomic (2D-electrophoresis, immunoblotting, LC-MS/MS) approaches. We showed that OMV proteins engaged exclusively in complement evasion and colonization strategies, but not those involved in iron transport and metabolism, are major targets for cross-reacting antibodies produced against phylogenetically divergent M...
March 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29459861/in-depth-analysis-of-human-neonatal-and-adult-igm-antibody-repertoires
#13
Binbin Hong, Yanling Wu, Wei Li, Xun Wang, Yumei Wen, Shibo Jiang, Dimiter S Dimitrov, Tianlei Ying
Although high-throughput sequencing and associated bioinformatics technologies have enabled the in-depth, sequence-based characterization of human immune repertoires, only a few studies on a relatively small number of sequences explored the characteristics of antibody repertoires in neonates, with contradictory conclusions. To gain a more comprehensive understanding of the human IgM antibody repertoire, we performed Illumina sequencing and IMGT/HighV-QUEST analysis of IgM heavy chain repertoire of the B lymphocytes from the cord blood (CB) of neonates, as well as the repertoire from peripheral blood of healthy human adults (HH)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29454089/genome-wide-gene-expression-analysis-of-45-days-pregnant-fetal-cotyledons-vis-a-vis-non-pregnant-caruncles-in-buffalo-bubalus-bubalis
#14
Masoud Lotfan, Syed Azmal Ali, Munna Lal Yadav, Suman Choudhary, Manoj Kumar Jena, Sudarshan Kumar, Ashok Kumar Mohanty
The crosstalk between fetus and mother starts with the onset of placental attachment to the uterus. The cotyledons and caruncles are the two anatomically distinct structures that play a crucial role in this physiological communication. Using Agilent Gene Chip Genome microarray, we measured the expression profile of pregnancy cotyledons in comparison to caruncular reminiscence of the uteri in non-pregnant buffalo (Bubalus bubalis) for the detection of the early post-pregnancy rapid changes in cellular expression of mRNA transcripts...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29325279/-characteristics-of-igh-cdr3-repertoire-of-peripheral-b-cells-in-a-patient-with-primary-biliary-cholangitis-a-preliminary-study-using-high-throughput-sequencing
#15
D T Zhao, C L Guo, H P Yan, H Y Liao, Y M Liu, H P Zhang, L S An, C Y Huang, Y Han, Y Zhao
Objective: To analyze the characteristics of immunoglobulin heavy chain complementarity-determining region (IgH-CDR3) repertoire of peripheral B cells in a patient with primary biliary cholangitis (PBC) and to investigate the diversity of the immune system. Methods: Arm-PCR was used to amplify the IgH-CDR3 region of circulating B cells isolated from a PBC patient, and high-throughput sequencing was used to analyze the amplified product. The characteristics of immune repertoire were analyzed by bioinformatics...
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29123524/vertebrate-adaptive-immunity-comparative-insights-from-a-teleost-model
#16
REVIEW
Harry W Dickerson, Robert Craig Findly
The channel catfish ( Ictalurus punctatus ) and the ciliated protozoan parasite Ichthyophthirius multifiliis are used to study pathogen-specific protective immunity. In this review, we briefly describe this host-parasite system and discuss the comparative insights it provides on the adaptive immune response of vertebrates. We include studies related to cutaneous mucosal immunity, B cell memory responses, and analyses of αβ T cell receptor (TCR) repertoires. This host-parasite model has played an important role in elucidating host protective responses to parasite invasion and for comparative studies of vertebrate immunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28823799/drosophila-mir-964-modulates-toll-signaling-pathway-in-response-to-bacterial-infection
#17
Shengjie Li, Jiao Xu, Lianjie Sun, Ruimin Li, Ping Jin, Fei Ma
Recent studies suggest that microRNA (miRNA) plays important roles in the control of immune response and tolerance. We previously found that the expression level of antimicrobial peptide gene Drosomycin (Drs) is decreased in miR-964 overexpressing flies. Here, we further verified that miR-964 deficiency leads to hyper-activation of Drs. In addition, we employed three widely-used bioinformatic algorithms to screen potential miR-964 targets. Finally, we identified that miR-964 modulates Toll signaling pathway, at least in part, by repressing the expression of Drs...
December 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28791125/nkg2c-memory-like-nk-cells-contribute-to-the-control-of-hiv-viremia-during-primary-infection-optiprim-anrs-147
#18
Françoise Gondois-Rey, Antoine Chéret, Samuel Granjeaud, Françoise Mallet, Ghislain Bidaut, Camille Lécuroux, Mickaël Ploquin, Michaela Müller-Trutwin, Christine Rouzioux, Véronique Avettand-Fenoël, Alessandro Moretta, Gilles Pialoux, Cécile Goujard, Laurence Meyer, Daniel Olive
Natural-killer (NK) cells are important immune effectors during a viral infection. Latent CMV infection is widely spread and was demonstrated to shape the NK cell repertoire through the NKG2C receptor. An expansion of NKG2C+ NK cells has been reported during primary HIV infection (PHI), but their role is not known. We previously found a correlation between the maturation state of the NK cell compartment and a lower viral load by studying patients from the ANRS 147 Optiprim trial. We investigated here extensively the NKG2C+ NK cells at the time of PHI and its evolution after 3 months of early antiretroviral therapy (combination antiretroviral therapy (cART))...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28747151/comparative-analysis-of-targeted-long-read-sequencing-approaches-for-characterization-of-a-plant-s-immune-receptor-repertoire
#19
COMPARATIVE STUDY
Michael Giolai, Pirita Paajanen, Walter Verweij, Kamil Witek, Jonathan D G Jones, Matthew D Clark
BACKGROUND: The Oxford Nanopore Technologies MinION™ sequencer is a small, portable, low cost device that is accessible to labs of all sizes and attractive for in-the-field sequencing experiments. Selective breeding of crops has led to a reduction in genetic diversity, and wild relatives are a key source of new genetic resistance to pathogens, usually via NLR immune receptor-encoding genes. Recent studies have demonstrated how crop NLR repertoires can be targeted for sequencing on Illumina or PacBio (RenSeq) and the specific gene conveying pathogen resistance identified...
July 26, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28706301/a-haystack-heuristic-for-autoimmune-disease-biomarker-discovery-using-next-gen-immune-repertoire-sequencing-data
#20
Leonard Apeltsin, Shengzhi Wang, H-Christian von Büdingen, Marina Sirota
Large-scale DNA sequencing of immunological repertoires offers an opportunity for the discovery of novel biomarkers for autoimmune disease. Available bioinformatics techniques however, are not adequately suited for elucidating possible biomarker candidates from within large immunosequencing datasets due to unsatisfactory scalability and sensitivity. Here, we present the Haystack Heuristic, an algorithm customized to computationally extract disease-associated motifs from next-generation-sequenced repertoires by contrasting disease and healthy subjects...
July 13, 2017: Scientific Reports
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