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  1. Article ; Online: tidytcells: standardizer for TR/MH nomenclature.

    Nagano, Yuta / Chain, Benjamin

    Frontiers in immunology

    2023  Volume 14, Page(s) 1276106

    Abstract: T cell receptors (TR) underpin the diversity and specificity of T cell activity. As such, TR repertoire data is valuable both as an adaptive immune biomarker, and as a way to identify candidate therapeutic TR. Analysis of TR repertoires relies heavily on ...

    Abstract T cell receptors (TR) underpin the diversity and specificity of T cell activity. As such, TR repertoire data is valuable both as an adaptive immune biomarker, and as a way to identify candidate therapeutic TR. Analysis of TR repertoires relies heavily on computational analysis, and therefore it is of vital importance that the data is standardized and computer-readable. However in practice, the usage of different abbreviations and non-standard nomenclature in different datasets makes this data pre-processing non-trivial. tidytcells is a lightweight, platform-independent Python package that provides easy-to-use standardization tools specifically designed for TR nomenclature. The software is open-sourced under the MIT license and is available to install from the Python Package Index (PyPI). At the time of publishing, tidytcells is on version 2.0.0.
    MeSH term(s) Receptors, Antigen, T-Cell ; Publishing ; Software
    Chemical Substances Receptors, Antigen, T-Cell
    Language English
    Publishing date 2023-10-25
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1276106
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Climate Change Affects Health: Are We Listening?

    Chain, Gabriel S / Chain, Benjamin M / Pelliccia, Frances B

    Global pediatric health

    2022  Volume 9, Page(s) 2333794X221091799

    Language English
    Publishing date 2022-04-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2785531-4
    ISSN 2333-794X ; 2333-794X
    ISSN (online) 2333-794X
    ISSN 2333-794X
    DOI 10.1177/2333794X221091799
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Application of T cell receptor (TCR) repertoire analysis for the advancement of cancer immunotherapy.

    Joshi, Kroopa / Milighetti, Martina / Chain, Benjamin M

    Current opinion in immunology

    2021  Volume 74, Page(s) 1–8

    Abstract: T cell receptor (TCR) sequencing has emerged as a powerful new technology in analysis of the host-tumour interaction. The advances in NextGen sequencing technologies, coupled with powerful novel bioinformatic tools, allow quantitative and reproducible ... ...

    Abstract T cell receptor (TCR) sequencing has emerged as a powerful new technology in analysis of the host-tumour interaction. The advances in NextGen sequencing technologies, coupled with powerful novel bioinformatic tools, allow quantitative and reproducible characterisation of repertoires from tumour and blood samples from an increasing number of patients with a variety of solid cancers. In this review, we consider how global metrics such as T cell clonality and diversity can be extracted from these repertoires and used to give insight into the mechanism of action of immune checkpoint blockade. Furthermore, we explore how the analysis of TCR overlap between repertories can help define spatial and temporal heterogeneity of the anti-tumoural immune response. Finally, we review how analysis of TCR sequence and structure, either of individual TCRs or from sets of related TCRs can be used to annotate the antigenic specificity, with important implications for the development of personalised adoptive cellular immunotherapies.
    MeSH term(s) Humans ; Immunotherapy ; Immunotherapy, Adoptive ; Neoplasms/therapy ; Receptors, Antigen, T-Cell/genetics ; T-Lymphocytes
    Chemical Substances Receptors, Antigen, T-Cell
    Language English
    Publishing date 2021-08-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2021.07.006
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2773: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  4. Article ; Online: Are patients with lung cystic fibrosis at increased risk of severe and fatal COVID-19? Interleukin 6 as a predictor of COVID-19 outcomes.

    Marcinkiewicz, Janusz / Mazurek, Henryk / Majka, Grzegorz / Chain, Benjamin

    Polish archives of internal medicine

    2020  Volume 130, Issue 10, Page(s) 919–920

    MeSH term(s) Betacoronavirus ; COVID-19 ; Coronavirus ; Coronavirus Infections ; Cystic Fibrosis ; Humans ; Immune System ; Interleukin-6 ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2
    Chemical Substances Interleukin-6
    Keywords covid19
    Language English
    Publishing date 2020-10-05
    Publishing country Poland
    Document type Letter ; Comment
    ZDB-ID 123500-x
    ISSN 1897-9483 ; 0032-3772
    ISSN (online) 1897-9483
    ISSN 0032-3772
    DOI 10.20452/pamw.15630
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 360: Show issues Location:
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  5. Article ; Online: The sequence of sequencers: The history of sequencing DNA.

    Heather, James M / Chain, Benjamin

    Genomics

    2016  Volume 107, Issue 1, Page(s) 1–8

    Abstract: Determining the order of nucleic acid residues in biological samples is an integral component of a wide variety of research applications. Over the last fifty years large numbers of researchers have applied themselves to the production of techniques and ... ...

    Abstract Determining the order of nucleic acid residues in biological samples is an integral component of a wide variety of research applications. Over the last fifty years large numbers of researchers have applied themselves to the production of techniques and technologies to facilitate this feat, sequencing DNA and RNA molecules. This time-scale has witnessed tremendous changes, moving from sequencing short oligonucleotides to millions of bases, from struggling towards the deduction of the coding sequence of a single gene to rapid and widely available whole genome sequencing. This article traverses those years, iterating through the different generations of sequencing technology, highlighting some of the key discoveries, researchers, and sequences along the way.
    MeSH term(s) High-Throughput Nucleotide Sequencing/history ; High-Throughput Nucleotide Sequencing/methods ; History, 20th Century ; History, 21st Century ; Nanotechnology/methods ; Sequence Analysis, DNA/history ; Sequence Analysis, DNA/methods
    Language English
    Publishing date 2016-01
    Publishing country United States
    Document type Historical Article ; Journal Article ; Review
    ZDB-ID 356334-0
    ISSN 1089-8646 ; 0888-7543
    ISSN (online) 1089-8646
    ISSN 0888-7543
    DOI 10.1016/j.ygeno.2015.11.003
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    Zs.A 2367: Show issues Location:
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  6. Article ; Online: The "Achilles' Heel" of Cancer and Its Implications for the Development of Novel Immunotherapeutic Strategies.

    Joshi, Kroopa / Chain, Benjamin M / Peggs, Karl S / Quezada, Sergio A

    Cold Spring Harbor perspectives in medicine

    2018  Volume 8, Issue 1

    Abstract: Over the last century, scientists have embraced the idea of mobilizing antitumor immune responses in patients with cancer. In the last decade, we have seen the rebirth of cancer immunotherapy and its validation in a series of high profile clinical trials ...

    Abstract Over the last century, scientists have embraced the idea of mobilizing antitumor immune responses in patients with cancer. In the last decade, we have seen the rebirth of cancer immunotherapy and its validation in a series of high profile clinical trials following the discovery of several immune-regulatory receptors. Recent studies point toward the tumor mutational load and resulting neoantigen burden as being crucial to tumor cell recognition by the immune system, highlighting a potentially targetable Achilles' heel in cancer. In this review, we explore the key mechanisms that underpin the recognition of cancerous cells by the immune system and discuss how we may advance immunotherapeutic strategies to target the cancer mutanome to stimulate tumor-specific immune responses, ultimately, to improve the clinical outcome for patients with cancer.
    MeSH term(s) Animals ; Antigens, Neoplasm/immunology ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; Humans ; Immunity, Humoral ; Immunologic Surveillance ; Immunotherapy/methods ; Mutation/immunology ; Neoplasms/immunology ; Neoplasms/therapy ; Tumor Microenvironment
    Chemical Substances Antigens, Neoplasm ; Antineoplastic Agents, Immunological
    Language English
    Publishing date 2018-01-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 2157-1422
    ISSN (online) 2157-1422
    DOI 10.1101/cshperspect.a027086
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  7. Article: X-ray crystallographic studies of RoAb13 bound to PIYDIN, a part of the N-terminal domain of C-C chemokine receptor 5.

    Govada, Lata / Saridakis, Emmanuel / Kassen, Sean C / Bin-Ramzi, Ahmad / Morgan, Rhodri Marc / Chain, Benjamin / Helliwell, John R / Chayen, Naomi E

    IUCrJ

    2021  Volume 8, Issue Pt 4, Page(s) 678–683

    Abstract: C-C chemokine receptor 5 (CCR5) is a major co-receptor molecule used by HIV-1 to enter cells. This led to the hypothesis that stimulating an antibody response would block HIV with minimal toxicity. Here, X-ray crystallographic studies of the anti-CCR5 ... ...

    Abstract C-C chemokine receptor 5 (CCR5) is a major co-receptor molecule used by HIV-1 to enter cells. This led to the hypothesis that stimulating an antibody response would block HIV with minimal toxicity. Here, X-ray crystallographic studies of the anti-CCR5 antibody RoAb13 together with two peptides were undertaken: one peptide is a 31-residue peptide containing the PIYDIN sequence and the other is the PIDYIN peptide alone, where PIYDIN is part of the N-terminal region of CCR5 previously shown to be important for HIV entry. In the presence of the longer peptide (the complete N-terminal domain), difference electron density was observed at a site within a hypervariable CDR3 binding region. In the presence of the shorter core peptide PIYDIN, difference electron density is again observed at this CDR3 site, confirming consistent binding for both peptides. This may be useful in the design of a new biomimetic to stimulate an antibody response to CCR5 in order to block HIV infection.
    Language English
    Publishing date 2021-07-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2754953-7
    ISSN 2052-2525
    ISSN 2052-2525
    DOI 10.1107/S2052252521005340
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  8. Article ; Online: Clonal expansion under the microscope: studying lymphocyte activation and differentiation using live-cell imaging.

    Polonsky, Michal / Chain, Benjamin / Friedman, Nir

    Immunology and cell biology

    2015  Volume 94, Issue 3, Page(s) 242–249

    Abstract: Clonal expansion of lymphocytes is a hallmark of vertebrate adaptive immunity. A small number of precursor cells that recognize a specific antigen proliferate into expanded clones, differentiate and acquire various effector and memory phenotypes, which ... ...

    Abstract Clonal expansion of lymphocytes is a hallmark of vertebrate adaptive immunity. A small number of precursor cells that recognize a specific antigen proliferate into expanded clones, differentiate and acquire various effector and memory phenotypes, which promote effective immune responses. Recent studies establish a large degree of heterogeneity in the level of expansion and in cell state between and within expanding clones. Studying these processes in vivo, while providing insightful information on the level of heterogeneity, is challenging due to the complex microenvironment and the inability to continuously track individual cells over extended periods of time. Live cell imaging of ex vivo cultures within micro fabricated arrays provides an attractive methodology for studying clonal expansion. These experiments facilitate continuous acquisition of a large number of parameters on cell number, proliferation, death and differentiation state, with single-cell resolution on thousands of expanding clones that grow within controlled environments. Such data can reveal stochastic and instructive mechanisms that contribute to observed heterogeneity and elucidate the sequential order of differentiation events. Intercellular interactions can also be studied within these arrays by following responses of a controlled number of interacting cells, all trapped within the same microwell. Here we describe implementations of live-cell imaging within microwell arrays for studies of lymphocyte clonal expansion, portray insights already gained from these experiments and outline directions for future research. These tools, together with in vivo experiments tracking single-cell responses, will expand our understanding of adaptive immunity and the ways by which it can be manipulated.
    MeSH term(s) Animals ; Cell Communication ; Cell Differentiation ; Cell Tracking/methods ; Clonal Evolution ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Lymphocyte Activation/immunology ; Lymphocytes/cytology ; Lymphocytes/physiology ; Microscopy/methods ; Single-Cell Analysis/methods
    Language English
    Publishing date 2015-12-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1038/icb.2015.104
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    Uc I Zs.175: Show issues Location:
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  9. Article ; Online: Executable network of SARS-CoV-2-host interaction predicts drug combination treatments.

    Howell, Rowan / Clarke, Matthew A / Reuschl, Ann-Kathrin / Chen, Tianyi / Abbott-Imboden, Sean / Singer, Mervyn / Lowe, David M / Bennett, Clare L / Chain, Benjamin / Jolly, Clare / Fisher, Jasmin

    NPJ digital medicine

    2022  Volume 5, Issue 1, Page(s) 18

    Abstract: The COVID-19 pandemic has pushed healthcare systems globally to a breaking point. The urgent need for effective and affordable COVID-19 treatments calls for repurposing combinations of approved drugs. The challenge is to identify which combinations are ... ...

    Abstract The COVID-19 pandemic has pushed healthcare systems globally to a breaking point. The urgent need for effective and affordable COVID-19 treatments calls for repurposing combinations of approved drugs. The challenge is to identify which combinations are likely to be most effective and at what stages of the disease. Here, we present the first disease-stage executable signalling network model of SARS-CoV-2-host interactions used to predict effective repurposed drug combinations for treating early- and late stage severe disease. Using our executable model, we performed in silico screening of 9870 pairs of 140 potential targets and have identified nine new drug combinations. Camostat and Apilimod were predicted to be the most promising combination in effectively supressing viral replication in the early stages of severe disease and were validated experimentally in human Caco-2 cells. Our study further demonstrates the power of executable mechanistic modelling to enable rapid pre-clinical evaluation of combination therapies tailored to disease progression. It also presents a novel resource and expandable model system that can respond to further needs in the pandemic.
    Language English
    Publishing date 2022-02-14
    Publishing country England
    Document type Journal Article
    ISSN 2398-6352
    ISSN (online) 2398-6352
    DOI 10.1038/s41746-022-00561-5
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  10. Article ; Online: Hybrid epidemics--a case study on computer worm conficker.

    Zhang, Changwang / Zhou, Shi / Chain, Benjamin M

    PloS one

    2015  Volume 10, Issue 5, Page(s) e0127478

    Abstract: Conficker is a computer worm that erupted on the Internet in 2008. It is unique in combining three different spreading strategies: local probing, neighbourhood probing, and global probing. We propose a mathematical model that combines three modes of ... ...

    Abstract Conficker is a computer worm that erupted on the Internet in 2008. It is unique in combining three different spreading strategies: local probing, neighbourhood probing, and global probing. We propose a mathematical model that combines three modes of spreading: local, neighbourhood, and global, to capture the worm's spreading behaviour. The parameters of the model are inferred directly from network data obtained during the first day of the Conficker epidemic. The model is then used to explore the tradeoff between spreading modes in determining the worm's effectiveness. Our results show that the Conficker epidemic is an example of a critically hybrid epidemic, in which the different modes of spreading in isolation do not lead to successful epidemics. Such hybrid spreading strategies may be used beneficially to provide the most effective strategies for promulgating information across a large population. When used maliciously, however, they can present a dangerous challenge to current internet security protocols.
    MeSH term(s) Computer Security ; Epidemics ; Internet ; Models, Theoretical
    Language English
    Publishing date 2015-05-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0127478
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