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Immunogenomics

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https://www.readbyqxmd.com/read/27828772/toward-a-reference-gene-catalog-of-human-primary-monocytes
#1
Hoda Mirsafian, Adiratna Mat Ripen, Thamilvaani Manaharan, Saharuddin Bin Mohamad, Amir Feisal Merican
Transcriptome analyses based on high-throughput RNA sequencing (RNA-Seq) provide powerful and quantitative characterization of cell types and in-depth understanding of biological systems in health and disease. In this study, we present a comprehensive transcriptome profile of human primary monocytes, a crucial component of the innate immune system. We performed deep RNA-Seq of monocytes from six healthy subjects and integrated our data with 10 other publicly available RNA-Seq datasets of human monocytes. A total of 1...
November 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27799140/endogenous-neoantigen-specific-cd8-t-cells-identified-in-two-glioblastoma-models-using-a-cancer-immunogenomics-approach
#2
Tanner M Johanns, Jeffrey P Ward, Christopher A Miller, Courtney Wilson, Dale K Kobayashi, Diane Bender, Yujie Fu, Anton Alexandrov, Elaine R Mardis, Maxim N Artyomov, Robert D Schreiber, Gavin P Dunn
The "cancer immunogenomics" paradigm has facilitated the search for tumor-specific antigens over the last 4 years by applying comprehensive cancer genomics to tumor antigen discovery. We applied this methodology to identify tumor-specific "neoantigens" in the C57BL/6-derived GL261 and VM/Dk-derived SMA-560 tumor models. Following DNA whole-exome and RNA sequencing, high-affinity candidate neoepitopes were predicted and screened for immunogenicity by ELISPOT and tetramer analyses. GL261 and SMA-560 harbored 4,932 and 2,171 nonsynonymous exome mutations, respectively, of which less than half were expressed...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27683556/immunogenomics-of-hypermutated-glioblastoma-a-patient-with-germline-pole-deficiency-treated-with-checkpoint-blockade-immunotherapy
#3
Tanner M Johanns, Christopher A Miller, Ian G Dorward, Christina Tsien, Edward Chang, Arie Perry, Ravindra Uppaluri, Cole Ferguson, Robert E Schmidt, Sonika Dahiya, George Ansstas, Elaine R Mardis, Gavin P Dunn
: We present the case of a patient with a left frontal glioblastoma with primitive neuroectodermal tumor features and hypermutated genotype in the setting of a POLE germline alteration. During standard-of-care chemoradiation, the patient developed a cervical spine metastasis and was subsequently treated with pembrolizumab. Shortly thereafter, the patient developed an additional metastatic spinal lesion. Using whole-exome DNA sequencing and clonal analysis, we report changes in the subclonal architecture throughout treatment...
November 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27531490/immunogenomic-engineering-of-a-plug-and-dis-play-hybridoma-platform
#4
Mark Pogson, Cristina Parola, William J Kelton, Paul Heuberger, Sai T Reddy
Hybridomas, fusions of primary mouse B cells and myelomas, are stable, rapidly-proliferating cell lines widely utilized for antibody screening and production. Antibody specificity of a hybridoma clone is determined by the immunoglobulin sequence of the primary B cell. Here we report a platform for rapid reprogramming of hybridoma antibody specificity by immunogenomic engineering. Here we use CRISPR-Cas9 to generate double-stranded breaks in immunoglobulin loci, enabling deletion of the native variable light chain and replacement of the endogenous variable heavy chain with a fluorescent reporter protein (mRuby)...
2016: Nature Communications
https://www.readbyqxmd.com/read/27516546/network-pharmacology-of-jak-inhibitors
#5
Devapregasan Moodley, Hideyuki Yoshida, Sara Mostafavi, Natasha Asinovski, Adriana Ortiz-Lopez, Peter Symanowicz, Jean-Baptiste Telliez, Martin Hegen, James D Clark, Diane Mathis, Christophe Benoist
Small-molecule inhibitors of the Janus kinase family (JAKis) are clinically efficacious in multiple autoimmune diseases, albeit with increased risk of certain infections. Their precise mechanism of action is unclear, with JAKs being signaling hubs for several cytokines. We assessed the in vivo impact of pan- and isoform-specific JAKi in mice by immunologic and genomic profiling. Effects were broad across the immunogenomic network, with overlap between inhibitors. Natural killer (NK) cell and macrophage homeostasis were most immediately perturbed, with network-level analysis revealing a rewiring of coregulated modules of NK cell transcripts...
August 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27399422/143%C3%A2-identification-of-neoantigen-specific-cd8-t-cells-in-two-murine-orthotopic-glioblastoma-models-using-cancer-immunogenomics
#6
Tanner M Johanns, Jeffrey Ward, Courtney Wilson, Dale K Kobayashi, Diane Bender, Yujie Fu, Anton Alexandrov, Maxim N Artyomov, Chris A Miller, Elaine R Mardis, Gavin P Dunn
INTRODUCTION: Our understanding of how immune-based strategies designed to enhance T-cell activation might effectively control glioblastoma progression has been limited by our ability to identify and monitor tumor-specific T cells. The "cancer immunogenomics" approach has facilitated the search for tumor-specific antigens over the past 4 years by applying comprehensive cancer genomics to tumor antigen discovery. We applied this methodology to identify tumor-specific "neoantigens" in preclinical brain tumor models susceptible to checkpoint immunotherapy...
August 2016: Neurosurgery
https://www.readbyqxmd.com/read/27387842/immunogenomics-of-gastrointestinal-nematode-infection-in-ruminants-breeding-for-resistance-to-produce-food-sustainably-and-safely
#7
REVIEW
T Sweeney, J P Hanrahan, M T Ryan, B Good
Gastrointestinal nematode (GIN) infection of ruminants represents a major health and welfare challenge for livestock producers worldwide. The emergence of anthelmintic resistance in important GIN species and the associated animal welfare concerns have stimulated interest in the development of alternative and more sustainable strategies aimed at the effective management of the impact of GINs. These integrative strategies include selective breeding using genetic/genomic tools, grazing management, biological control, nutritional supplementation, vaccination and targeted selective treatment...
September 2016: Parasite Immunology
https://www.readbyqxmd.com/read/27297497/vdjviz-a-versatile-browser-for-immunogenomics-data
#8
Dmitriy V Bagaev, Ivan V Zvyagin, Ekaterina V Putintseva, Mark Izraelson, Olga V Britanova, Dmitriy M Chudakov, Mikhail Shugay
BACKGROUND: The repertoire of T- and B-cell receptor sequences encodes the antigen specificity of adaptive immunity system, determines its present state and guides its ability to mount effective response against encountered antigens in future. High throughput sequencing of immune repertoires (Rep-Seq) is a promising technique that allows to profile millions of antigen receptors of an individual in a single experiment. While a substantial number of tools for mapping and assembling Rep-Seq data were published recently, the field still lacks an intuitive and flexible tool that can be used by researchers with little or no computational background for in-depth analysis of immune repertoire profiles...
2016: BMC Genomics
https://www.readbyqxmd.com/read/27153063/a-brief-review-of-computer-assisted-approaches-to-rational-design-of-peptide-vaccines
#9
REVIEW
Ashesh Nandy, Subhash C Basak
The growing incidences of new viral diseases and increasingly frequent viral epidemics have strained therapeutic and preventive measures; the high mutability of viral genes puts additional strains on developmental efforts. Given the high cost and time requirements for new drugs development, vaccines remain as a viable alternative, but there too traditional techniques of live-attenuated or inactivated vaccines have the danger of allergenic reactions and others. Peptide vaccines have, over the last several years, begun to be looked on as more appropriate alternatives, which are economically affordable, require less time for development and hold the promise of multi-valent dosages...
May 4, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27084102/cytokine-like-1-chemoattracts-monocytes-macrophages-via-ccr2
#10
Xiaolin Wang, Ting Li, Wenyan Wang, Wanqiong Yuan, Huihui Liu, Yingying Cheng, Pingzhang Wang, Yu Zhang, Wenling Han
Cytokine-like 1 (CYTL1) is a novel potential cytokine that was first identified in CD34(+) cells derived from bone marrow and cord blood, and it was also found using our immunogenomics strategy. The immunobiological functions of CYTL1 remain largely unknown, and its potential receptor(s) has not been identified. A previous proposed hypothesis suggested that CYTL1 had structural similarities with CCL2 and that CCR2 was a potential receptor of CYTL1. In this study, we verify that CYTL1 possesses chemotactic activity and demonstrate that its functional receptor is CCR2B using a series of experiments performed in HEK293 cells expressing CCR2B or CCR2B-EGFP, including chemotaxis, receptor internalization, and radioactive binding assays...
May 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27070898/harnessing-the-immune-system-for-the-treatment-of-melanoma-current-status-and-future-prospects
#11
Andrea Guennoun, Heba Sidahmed, Cristina Maccalli, Barbara Seliger, Francesco M Marincola, Davide Bedognetti
When malignant melanoma is diagnosed early, surgical resection is the intervention of choice and is often curative, but many patients present with unresectable disease at later stages. Due to its complex etiology paired with well-documented chemoresistance and high metastatic potential, patients with advanced melanoma had a poor prognosis, and the treatment of this disease remained unsatisfactory for many years. Recently, targeted therapy, immune checkpoint inhibition, or combinatory approaches have revolutionized the therapeutic options of melanoma allowing considerable improvement in disease control and survival...
August 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/26934552/immunogenomics-reveal-molecular-circuits-of-diclofenac-induced-liver-injury-in-mice
#12
Eun-Hee Lee, Jung-Hwa Oh, Saravanakumar Selvaraj, Se-Myo Park, Mi-Sun Choi, Reinhard Spanel, Seokjoo Yoon, Jürgen Borlak
Diclofenac is a non-steroidal anti-inflammatory drug and its use can be associated with severe adverse reactions, notably myocardial infarction, stroke and drug-induced liver injury (DILI). In pursue of immune-mediated DILI mechanisms an immunogenomic study was carried out. Diclofenac treatment of mice at 30 mg/kg for 3 days caused significant serum ALT and AST elevations, hepatomegaly and degenerative changes including hepatic glycogen depletion, hydropic swelling, cholesterolosis and eosinophilic hepatocytes with one animal presenting subsegmental infarction due to portal vein thrombosis...
March 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/26819449/pan-cancer-immunogenomic-perspective-on-the-tumor-microenvironment-based-on-pd-l1-and-cd8-t-cell-infiltration
#13
Chan-Young Ock, Bhumsuk Keam, Sehui Kim, Ju-Seog Lee, Miso Kim, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Doo Hyun Chung, Dae Seog Heo
PURPOSE: There is currently no reliable biomarker to predict who would benefit from anti-PD-1/PD-L1 inhibitors. We comprehensively analyzed the immunogenomic properties in The Cancer Genome Atlas (TCGA) according to the classification of tumor into four groups based on PD-L1 status and tumor-infiltrating lymphocyte recruitment (TIL), a combination that has been suggested to be a theoretically reliable biomarker of anti-PD-1/PD-L1 inhibitors. EXPERIMENTAL DESIGN: The RNA expression levels of PD-L1 and CD8A in the samples in the pan-cancer database of TCGA (N = 9,677) were analyzed...
May 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26708359/bridging-immunogenomic-data-analysis-workflow-gaps-bigdawg-an-integrated-case-control-analysis-pipeline
#14
Derek J Pappas, Wesley Marin, Jill A Hollenbach, Steven J Mack
Bridging ImmunoGenomic Data-Analysis Workflow Gaps (BIGDAWG) is an integrated data-analysis pipeline designed for the standardized analysis of highly-polymorphic genetic data, specifically for the HLA and KIR genetic systems. Most modern genetic analysis programs are designed for the analysis of single nucleotide polymorphisms, but the highly polymorphic nature of HLA and KIR data require specialized methods of data analysis. BIGDAWG performs case-control data analyses of highly polymorphic genotype data characteristic of the HLA and KIR loci...
March 2016: Human Immunology
https://www.readbyqxmd.com/read/26582413/immunogenomics-a-foundation-for-intelligent-immune-design
#15
EDITORIAL
Robert A Holt
The complexity of the immune system is now being interrogated using methodologies that generate extensive multi-dimensional data. Effective collection, integration and interpretation of these data remain difficult, but overcoming these important challenges will provide new insights into immune function and opportunities for the rational design of new immune interventions.
November 19, 2015: Genome Medicine
https://www.readbyqxmd.com/read/26407912/minimum-information-for-reporting-next-generation-sequence-genotyping-miring-guidelines-for-reporting-hla-and-kir-genotyping-via-next-generation-sequencing
#16
Steven J Mack, Robert P Milius, Benjamin D Gifford, Jürgen Sauter, Jan Hofmann, Kazutoyo Osoegawa, James Robinson, Mathijs Groeneweg, Gregory S Turenchalk, Alex Adai, Cherie Holcomb, Erik H Rozemuller, Maarten T Penning, Michael L Heuer, Chunlin Wang, Marc L Salit, Alexander H Schmidt, Peter R Parham, Carlheinz Müller, Tim Hague, Gottfried Fischer, Marcelo Fernandez-Viňa, Jill A Hollenbach, Paul J Norman, Martin Maiers
The development of next-generation sequencing (NGS) technologies for HLA and KIR genotyping is rapidly advancing knowledge of genetic variation of these highly polymorphic loci. NGS genotyping is poised to replace older methods for clinical use, but standard methods for reporting and exchanging these new, high quality genotype data are needed. The Immunogenomic NGS Consortium, a broad collaboration of histocompatibility and immunogenetics clinicians, researchers, instrument manufacturers and software developers, has developed the Minimum Information for Reporting Immunogenomic NGS Genotyping (MIRING) reporting guidelines...
December 2015: Human Immunology
https://www.readbyqxmd.com/read/26341041/-development-of-new-vaccines
#17
Fernando González-Romo, Juan J Picazo
Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost...
October 2015: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/26319908/histoimmunogenetics-markup-language-1-0-reporting-next-generation-sequencing-based-hla-and-kir-genotyping
#18
Robert P Milius, Michael Heuer, Daniel Valiga, Kathryn J Doroschak, Caleb J Kennedy, Yung-Tsi Bolon, Joel Schneider, Jane Pollack, Hwa Ran Kim, Nezih Cereb, Jill A Hollenbach, Steven J Mack, Martin Maiers
We present an electronic format for exchanging data for HLA and KIR genotyping with extensions for next-generation sequencing (NGS). This format addresses NGS data exchange by refining the Histoimmunogenetics Markup Language (HML) to conform to the proposed Minimum Information for Reporting Immunogenomic NGS Genotyping (MIRING) reporting guidelines (miring.immunogenomics.org). Our refinements of HML include two major additions. First, NGS is supported by new XML structures to capture additional NGS data and metadata required to produce a genotyping result, including analysis-dependent (dynamic) and method-dependent (static) components...
December 2015: Human Immunology
https://www.readbyqxmd.com/read/26142251/the-immunogenetics-of-multiple-sclerosis-a-comprehensive-review
#19
REVIEW
Jill A Hollenbach, Jorge R Oksenberg
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and common cause of non-traumatic neurological disability in young adults. The likelihood for an individual to develop MS is strongly influenced by her or his ethnic background and family history of disease, suggesting that genetic susceptibility is a key determinant of risk. Over 100 loci have been firmly associated with susceptibility, whereas the main signal genome-wide maps to the class II region of the human leukocyte antigen (HLA) gene cluster and explains up to 10...
November 2015: Journal of Autoimmunity
https://www.readbyqxmd.com/read/26140055/a-bioinformatic-framework-for-immune-repertoire-diversity-profiling-enables-detection-of-immunological-status
#20
Victor Greiff, Pooja Bhat, Skylar C Cook, Ulrike Menzel, Wenjing Kang, Sai T Reddy
BACKGROUND: Lymphocyte receptor repertoires are continually shaped throughout the lifetime of an individual in response to environmental and pathogenic exposure. Thus, they may serve as a fingerprint of an individual's ongoing immunological status (e.g., healthy, infected, vaccinated), with far-reaching implications for immunodiagnostics applications. The advent of high-throughput immune repertoire sequencing now enables the interrogation of immune repertoire diversity in an unprecedented and quantitative manner...
2015: Genome Medicine
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