Publications by authors named "Kerry Mullan"

Article Synopsis
  • T cells and their receptors (TCRs) are essential for understanding immune responses but are often overlooked in single-cell analysis, which typically focuses on gene expression.
  • The authors created a comprehensive T cell atlas from 12 major studies, involving 500,000 T cells across various diseases, and found challenges in accurately labeling cell types using standard methods.
  • They propose a TCR-first approach, using a semi-supervised method, to better identify T cell characteristics and dynamics, potentially enhancing immunotherapy and diagnostic strategies.
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  • * A study analyzed genetic data from UK Biobank patients with shingles, focusing on immune responses and risk factors, uncovering significant links between susceptibility and human leukocyte antigens (HLAs).
  • * Key findings indicate that variations in the major histocompatibility complex play a crucial role in developing shingles, alongside increased immune responses related to type I interferon, offering new insights into how VZV reactivation affects the immune system.
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  • Single-cell RNA sequencing (scRNA-seq) is a powerful technique for analyzing gene expression diversity in cells, particularly useful for studying complex cell populations like T cells.
  • Unlike bulk RNA sequencing, scRNA-seq can identify specific subtypes within these populations and recently enables simultaneous analysis of T-cell receptor (TCR) sequences alongside gene expression.
  • However, the analysis of scRNA-seq data faces challenges due to the lack of reliable methods for accurately annotating T-cell subtypes, as existing tools struggle to differentiate between the various T-cell populations effectively.
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The immune system acts as an intricate apparatus that is dedicated to mounting a defense and ensures host survival from microbial threats. To engage this faceted immune response and provide protection against infectious diseases, vaccinations are a critical tool to be developed. However, vaccine responses are governed by levels that, when interrogated, separately only explain a fraction of the immune reaction.

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Allopurinol (ALP) is a successful drug used in the treatment of gout. However, this drug has been implicated in hypersensitivity reactions that can cause severe to life-threatening reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Individuals who carry the human leukocyte antigen (HLA)-B*58:01 allotype are at higher risk of experiencing a hypersensitivity reaction (odds ratios ranging from 5.

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Despite the general agreement on the significance of T cells during SARS-CoV-2 infection, the clinical impact of specific and cross-reactive T-cell responses remains uncertain. Understanding this aspect could provide insights for adjusting vaccines and maintaining robust long-term protection against continuously emerging variants. To characterize CD8+ T-cell response to SARS-CoV-2 epitopes unique to the virus (SC2-unique) or shared with other coronaviruses (CoV-common), we trained a large number of T-cell receptor (TCR) - epitope recognition models for MHC-I-presented SARS-CoV-2 epitopes from publicly available data.

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T cells expressing either alpha-beta or gamma-delta T cell receptors (TCR) are critical sentinels of the adaptive immune system, with receptor diversity being essential for protective immunity against a broad array of pathogens and agents. Programs available to profile TCR clonotypic signatures can be limiting for users with no coding expertise. Current analytical pipelines can be inefficient due to manual processing steps, open to data entry errors and have multiple analytical tools with unique inputs that require coding expertise.

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Article Synopsis
  • Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe skin reactions that can be triggered by certain antiseizure medications, particularly carbamazepine, especially in individuals with the HLA-B*15:02 allele, which is seen in many Asians.
  • Researchers analyzed the genomes of people affected by SJS/TEN and identified nine significant genetic variants that increase the risk of these reactions, some being independent of the HLA-B*15:02 status.
  • The study highlights that genetic variations, particularly in regulatory regions of DNA, may influence susceptibility to SJS/TEN by altering the regulation of genes associated with the disease, indicating a complex relationship between genetics and drug reactions.
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Volcano and other analytical plots (e.g., correlation plots, upset plots, and heatmaps) serve as important data visualization methods for transcriptomic and proteomic analyses.

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Peptide vaccination remains a viable approach to induce T-cell mediated killing of tumors. To identify potential T-cell targets for Triple-Negative Breast Cancer (TNBC) vaccination, we examined the effect of the pro-inflammatory cytokine interferon-γ (IFNγ) on the transcriptome, proteome, and immunopeptidome of the TNBC cell line MDA-MB-231. Using high resolution mass spectrometry, we identified a total of 84,131 peptides from 9,647 source proteins presented by human leukocyte antigen (HLA)-I and HLA-II alleles.

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Adverse drug reactions (ADRs) are a common cause of hospital admissions (up to 19%), with the majority of cases due to off-target predictable drug effects (type A reactions). However, idiosyncratic drug-induced immune activated (type B) reactions contribute to a range of hypersensitivity reactions, with T-cell-mediated type IV hypersensitivity reactions mainly manifesting as cutaneous ADRs (cADRs). Aromatic antiepileptic drugs (AEDs), used in the treatment of epilepsy as well as bipolar disorder or neuropathic pain, have been implicated as culprit drugs in a spectrum of pathologies ranging from mild maculopapular exanthema (MPE) to severe and life-threatening conditions including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

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