DR61 DataRelease
Release Date: Frebruary 2026
New Studies: 7
Updated Studies: 2
New Studies
| SDY3090: PDI-TCR reveals the dynamics and phenotypes of CD4 T cells in tuberculosis | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | Identifying antigen specificity in T cell receptor (TCR) sequences is challenging because of the diversity of the TCR repertoire and the complexity of TCR:antigen recognition. We developed the Peptide-Driven Identification of TCRs (PDI-TCR) assay, which combines in vitro cell expansion with peptide pools, bulk TCR sequencing, and statistical analysis to identify antigen-specific TCRs from human blood. PDI-TCR can differentiate true antigen-specific TCR clonotypes from TCRs linked to nonspecific bystander activation by comparing responses to non-overlapping peptide pools. We applied PDI-TCR to Tuberculosis (TB) patients, sampling blood at diagnosis and during treatment, as well as to Mycobacterium tuberculosis (Mtb)-sensitized healthy individuals (IGRA+). Mtb-specific T cells exhibited high diversity, with short-lived effector phenotypes only present in TB at diagnosis, while memory phenotypes were sustained throughout treatment. In contrast, expanded nonspecific T cells were more clonally restricted, displayed a cytotoxic phenotype, and persisted during treatment. | |||||||||||||||
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| DOI: | 10.21430/M35YWYAEUK | |||||||||||||||
| Subjects: | 65 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
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| SDY3153: Single Cell Transcriptomics and Immune Profiling in Cutaneous Lyme Disease | |||||||||
| Status: | New | ||||||||
| Description: | The skin lesion erythema migrans (EM) is the first clinical sign of Lyme disease, an infection due to the tick-transmitted bacterium Borrelia burgdorferi (Bb). Previously we used single cell transcriptomics with B cell and T cell receptor sequencing to characterize the cutaneous immune response in the EM lesion, focusing on B cells. Here, in an expanded sample size, we profiled T cell responses in the EM lesions in comparison to autologous uninvolved skin. In addition to CD4+IFNG+ T cell subsets known to be abundant in the EM, we identified clonal expansion of CD8+GZMK+IFNG+ T cells that comprised the only T cell population with significant differential expression of interferon regulated genes. This subset included IFNG+ cells with low cytotoxic gene expression, which may promote inflammation. While FOXP3+ regulatory T cells also were increased in EM, we found that the CD4+FOXP3- effector T cell subset contained cells with the highest differential expression of IL-10. Fibroblasts, endothelial cells, and pericytes expressed a broader array of chemokines than macrophages. These studies represent the first comprehensive interrogation of the cutaneous T cell response to Bb infection using single cell transcriptomics and provide insight into the orchestration of the skin immune response to this vector-borne pathogen. |
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| DOI: | 10.21430/M365I7LZQU | ||||||||
| Subjects: | 7 | ||||||||
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| Publications: | None | ||||||||
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| Clinical Assessments: | None | ||||||||
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| SDY3238: Immunostimulatory RNA motifs_1 | |||||||
| Status: | New | ||||||
| Description: | Detection of foreign RNAs is a crucial activation step for innate immunity pathways in response to viral infections. Retinoic acid-inducible gene I (RIG-I) is a cytoplasmic RNA sensor that triggers type I and III interferon (IFN) expression and activates the antiviral response. The activating ligand for RIG-I has been shown to be 5’-triphosphated blunt-ended double stranded(ds) RNA, but questions remain on the molecular mechanisms for RIG-I activation during viral infections. We have previously determined that the RNA that most robustly activates RIG-I signaling during Sendai Virus (SeV) infection is a copy-back viral genome (cbVG). CbVGs contain complementary ends long predicted to form a blunt-ended dsRNA PAMP with a 5’ triphosphate, characteristic of the canonical RIG-I ligand. However, detailed folding analyses of the most prominent cbVG from SeV (cbVG 546) revealed a much more complex folding of the molecule, including a stem loop that is necessary for strong activation of the RIG-I pathway to stimulate IFN expression. This stem loop is comprised of nucleotides 70-114 of cbVG 546, and when transferred to inert RNAs, it significantly enhanced the immunostimulatory capability of the RNA. Interestingly, the removal of stem loop 70-114 from cbVG 546 severely decreased RIG-I activation even though the cbVG still contained the 5’ triphosphate and blunt-end dsRNA. It is unknown how SeV 70-114 enhanced RIG-I activity or whether other RIG-I stimulatory cbVGs contain stem loops similar to SeV 70-114. We therefore sought to determine if other viral cbVGs contain RNA stem loops that can transfer RIG-I stimulatory activity to otherwise inert RNAs and identify features of these RNA stem loops that are necessary for robust RIG-I activation. We identified multiple sequences in cbVGs from human respiratory syncytial virus (RSV) and Nipah virus (NiV) infections that can transfer RIG-I stimulatory activity to the inert X RNA from the hepatitis C virus. Through mutation of the terminal loop sequences of the cbVG-derived RNAs, we discovered that specific nucleotides in the terminal loop of the RNA are necessary for strong activation of RIG-I signaling in cells. Lastly, in vivo administration of the cbVG-derived RNA loops activated innate immune signaling pathways, suggesting their potential use as immunostimulants for vaccines and immunotherapies. | ||||||
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| DOI: | 10.21430/M3H49C0CP5 | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
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| SDY3385: Household Cohort Study in New Zealand | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | New | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description: | To examine transmission of and susceptibility to influenza virus in a longitudinal household cohort study in Wellington, New Zealand. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M39TNF6A3G | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | 3165 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| SDY3403: CyTOF analysis of HER2 expression in PC9 EGFR mutant NSCLC preclinical model following osimertinib treatments. | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Tumours were collected 2 hour post last dose, digested to single cells and stained with platinium viability marker. The samples were barcoded with 20 plex Pd kit and stained with panel of antibodies including HER2. The samples were acquired by the CyTOF XT and live cells were gated. Tumour cells were clustered using HLA-ABC, EpCAM, pan-cytokeratin and E-cadherin. Expression of HER2 was quantified | ||||||||||||
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| DOI: | 10.21430/M3XOEAC30E | ||||||||||||
| Subjects: | 19 | ||||||||||||
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| Publications: | None | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
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| SDY3408: De novo generation of SeV copy-back species | |||||||
| Status: | New | ||||||
| Description: | Copy-back viral genomes (cbVGs) are generated during the replication of negative-sense RNA viruses when the polymerase drops off from the genome and reattaches to the nascent strand. cbVGs have strong immunostimulatory properties and impact infection outcomes. Despite their importance, the composition and mechanisms of de novo cbVG generation and accumulation remain unclear due to challenges in obtaining cbVG-free virus stocks (clean stocks). Here, we obtained several clean stocks by independently rescuing recombinant Sendai virus (SeV) six times and verified their cleanliness through PCR, RNA sequencing, and absence of immunostimulatory activity. High multiplicity-of-infection passaging of clean stocks produced six high-MOI passaged stocks, each with distinct cbVG populations. Among them, polymerase drop-off (break) positions occurred throughout the genome, while polymerase reattachment (rejoin) positions preferentially occurring near the trailer end. Few common breaks were observed between stocks, while there was a hot rejoin region near the trailer end. In each stock, a few cbVGs species dominated and remained stable across passages, all conforming to the ‘rule of six’, regardless of length. Low-abundance cbVGs were variable across passages, indicating the continuous generation of new cbVGs, despite the stabilization of a subset of species. Intriguingly, cbVG species which originated from polymerase drop-off at or close to nucleotide 1 were present in all stocks, suggesting that cbVG species originating at the 3’ end of the genome are conserved products of SeV replication | ||||||
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| DOI: | 10.21430/M3AHP0C2JC | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
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| SDY3419: Flow Cytometry of Immune populations in tumor tissue | |||||||
| Status: | New | ||||||
| Description: | During the last years, it became more and more apparent that the immune system greatly affects the activity of many anticancer therapies, often resulting in enhanced therapy efficacy. The drug class of anticancer thiosemicarbazones (TSCs) has been studied in several clinical trials including a promising combination with the regularly used chemotherapy cisplatin and radiation therapy, which are both known to modulate the immune system in a favorable way. However, no investigations regarding the effect of TSCs on the anticancer immune response were conducted so far. Consequently, the aim of this study is to assess the role of the immune system in TSC activity. Our preliminary results already indicated that especially the adaptive arm of the immune system is crucial for TSC anticancer activity. Therefore, in this study, the underlying mechanisms will be elaborated in more detail. In addition, we will investigate whether the clinical combination of TSCs with cisplatin results in an even higher enhancement of the anticancer immune response. To this end, we will employ diverse high-end techniques in a translational scientific network setting. An important part of the project will be the single cell analysis by flow cytometry of immune cells either located in (TSC-treated) tumor tissue or isolated from cell co-cultures with tumor cells. To that end, the identification markers on the surface of the immune cells are labeled with specific fluorescent antibodies to divide them for their different roles and activation states. The labels of each single cell will then be excited by lasers and fluorescence intensities will be measured by the sensitive detectors of flow cytometer. This will give us an overview of the changes occurring in tumor-associated immune cells during TSC therapy. Furthermore, immune cell migration and tumor infiltration will be observed in real-time. For this purpose, a genetically modified model system will be used that possesses immune cells which can be stimulated to produce bioluminescence. For more in-depth analysis, cell culture and biochemical methods will be applied to illuminate the molecular mechanism by which TSCs modulate the immune system. The project will enable us to elucidate the, until now not investigated, role of the immune system in the anticancer activity of clinically developed TSCs, which will result in a better understanding of the mechanism of these anticancer compounds as well as enable the design of improved therapy strategies. | ||||||
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| DOI: | 10.21430/M3BOSX974F | ||||||
| Subjects: | 16 | ||||||
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| Clinical Assessments: | None | ||||||
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Updated Studies
| SDY2187: Microbiome Preterm Birth DREAM Challenge | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Updated | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description: | Globally, every year about 11% of infants are born preterm, defined as a birth prior to 37 weeks of gestation, with significant and lingering health consequences. Multiple studies have related the vaginal microbiome to preterm birth. We present a crowdsourcing approach to predict: (a) preterm or (b) early preterm birth from 9 publicly available vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from raw sequences via an open-source tool, MaLiAmPi. We validated the crowdsourced models on novel datasets representing 331 samples from 148 pregnant individuals. From 318 DREAM challenge participants we received 148 and 121 submissions for our two separate prediction sub-challenges with top-ranking submissions achieving bootstrapped AUROC scores of 0.69 and 0.87, respectively. Alpha diversity, VALENCIA community state types, and composition (via phylotype relative abundance) were important features in the top performing models, most of which were tree based methods. This work serves as the foundation for subsequent efforts to translate predictive tests into clinical practice, and to better understand and prevent preterm birth. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M3JMMPMLSP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | 750 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Assays: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clinical Assessments: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| SDY2507: Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis (StopRA) - ARA08 | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease that affects ~1% of the population, making it one of the most common chronic autoimmune diseases. The hallmark of RA is synovial inflammation (synovitis) that leads to joint destruction. RA primarily affects the joints, with small joints being the primary joints involved; however, multiple other systems including respiratory tract (e.g. interstitial lung disease), cardiovascular system (e.g. myocardial infarction) and bones (e.g. osteoporosis) can be affected. Recent studies have shown that there are markers in the blood called 'autoantibodies' that precede the onset of joint symptoms of RA. Antibodies are commonly made in the blood to fight infections. Sometimes, these antibodies attack one's own body. These are called autoantibodies. The autoantibody known as anti-CCP3 is specific for RA and may predict the development of RA in the future, especially if the level of anti-CCP3 is high. Hydroxychloroquine (HCQ) has been used successfully and safely in the treatment of malaria, lupus and RA. The objective of this study is to determine whether treatment with HCQ in individuals with elevations of anti-CCP3 without joint inflammation may help prevent the future onset of RA. This is a phase 2 multi-center, randomized, placebo-controlled, double-blind, clinical trial to evaluate the effectiveness and safety of intervention with a 12-month course of HCQ to prevent the future onset of clinically-apparent RA | ||||||||||||
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| DOI: | 10.21430/M3H5058PJ3 | ||||||||||||
| Subjects: | 252 | ||||||||||||
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| Publications: | None | ||||||||||||
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