Biology subjects

Rainbow, D. B.

Publications and source records attributed to Rainbow, D. B..

8 recordsLinked to original sources

bioRxiv2026

The Human Gut Cell Atlas v1.0: A Unified, Community-BuiltReference of Cellular Diversity Across the Gut

Single-cell RNA-sequencing (scRNA-seq) studies have transformed our understanding of cellular diversity in the human intestine, but differences in anatomical sampling, experimental processing and cell-type nomenclature limit comparison across datasets. Here, we present the Human Gut Cell Atlas (HGCA) V1, a community-curated reference of 944,390 healthy and disease-adjacent intestinal cells from 502 samples, 265 donors and 24 landmark studies, linked to detailed anatomical, clinical, and technical metadata. As this metadata is of critical importance to human biology, we developed MetaManager, an open source data management framework for standardized metadata collection and tracking. A five-level consensus taxonomy resolves 94 homeostatic cell identities and enables transferrable, high-resolution annotation of new gut datasets. By assembling cell identity, sampling metadata, and independent spatial validation, intestinal segment and radial tissue depth were revealed to systematically shape cellular composition and transcriptional state, enabling inference of the presence of sampling-dependent tissue niches, including lymphoid follicles. Reference mapping accurately and rapidly recovered cohort-level Crohn's disease and treatment signatures without de novo annotation, while mapping human intestinal organoids quantified cell-type-specific identity, regional specification, maturation, and transcriptional fidelity to native tissue. The HGCA V1 provides a standardized cellular, anatomical coordinate, and metadata system for reproducible, high-quality analysis of intestinal biology across healthy tissue, disease-associated remodelling, and experimental models, providing a continuously evolving community reference for cumulative discovery in human intestinal biology.

systems biology↗

bioRxiv2025

Activation of transposable elements is linked to a region- and cell-type-specific interferon response in Parkinson's disease

Parkinsons disease (PD) is a neurodegenerative disorder involving a neuroinflammatory response, the cause of which remains unclear. Transposable elements (TE) have been linked to inflammation, but their potential role in PD remains unexplored. Using bulk- and single-nuclei RNAseq of postmortem brain tissue from four brain regions, we studied TE transcription and its correlation with PD neuroinflammation. Over a thousand TEs, including LINE-1s and ERVs, were expressed in a cell-type and region-specific manner in the human brain. Increased TE expression was found in microglia and neurons in the substantia nigra and putamen of PD brains, but not amygdala or prefrontal cortex, compared to controls. This TE activation correlated with an innate immune response in the same brain regions. The link between an interferon response and TE activation was mechanistically confirmed using human pluripotent stem cell-derived microglia and neurons. Our findings provide insights into TE transcription in the PD brain and suggest TEs may contribute to neuroinflammation and pathological progression in PD. Teaser: Transposable elements are linked to a cell type specific inflammatory state in Parkinsons Disease.

neuroscience↗

bioRxiv2023

Hiding in Plain Sight: Thymic CD8+FOXP3+Tregs sequester CD25 and are enriched in human tissues

For decades, regulatory T cell (Treg) research has focussed on CD4+FOXP3+ Tregs, while characterisation of CD8+FOXP3+ Tregs has been limited due to their scarcity in blood. Here, by analysing 95 tissue samples from 26 deceased transplant organ donors we show that, despite representing less than 5% of circulating Tregs, CD8+ Tregs are enriched in human tissue, particularly in non-lymphoid tissues and bone marrow. We further show that they are fully demethylated at the FOXP3 TSDR, indicating lineage stability, and demonstrate their presence in human thymic tissue and cord blood. Transcriptomic profiling revealed strong similarities to CD4+ Tregs, however at the protein level, they reside in tissue as surface CD25lo/-CD8+CD69+CD103+TLR9+HELIOS+FOXP3+ cells, expressing CD25 intracellularly. Surface CD25 was rapidly regained ex-vivo, allowing us to sort and expand them, and to subsequently demonstrate their therapeutic potential in a humanised mouse model of graft-vs-host disease. Additionally we report increased circulating CD8+Tregs in individuals with SLE and patients early following traumatic brain injury (TBI), underscoring their functional importance. We conclude that these under-studied cells likely play an essential but previously unappreciated role in maintaining peripheral tolerance. One Sentence SummaryFOXP3+CD8+ Tregs, expressing tissue residency markers and intracellular CD25, are enriched in human non-lymphoid tissues.

immunology↗

bioRxiv2023

FlowAtlas.jl: an interactive tool bridging FlowJo with computational tools in Julia

As the dimensionality, throughput, and complexity of cytometry data increases, so does the demand for user-friendly, interactive analysis tools that leverage high-performance machine learning frameworks. Here we introduce FlowAtlas.jl: an interactive web application that bridges the user-friendly environment of FlowJo and computational tools in Julia developed by the scientific machine learning community. We demonstrate the capabilities of FlowAtlas using a novel human multi-tissue, multi-donor immune cell dataset, highlighting key immunological findings.

bioinformatics↗

bioRxiv2019

Sharing information between related diseases using Bayesian joint fine mapping increases accuracy and identifies novel associations in six immune mediated diseases

Thousands of genetic variants have been associated with human disease risk, but linkage disequilibrium (LD) hinders fine-mapping the causal variants. We show that stepwise regression, and, to a lesser extent, stochastic search fine mapping can mis-identify as causal, SNPs which jointly tag distinct causal variants. Frequent sharing of causal variants between immune-mediated diseases (IMD) motivated us to develop a computationally efficient multinomial fine-mapping (MFM) approach that borrows information between diseases in a Bayesian framework. We show that MFM has greater accuracy than single disease analysis when shared causal variants exist, and negligible loss of precision otherwise. Applying MFM to data from six IMD revealed causal variants undetected in individual disease analysis, including in IL2RA where we confirm functional effects of multiple causal variants using allele-specific expression in sorted CD4+ T cells from genotype-selected individuals. MFM has the potential to increase fine-mapping resolution in related diseases enabling the identification of associated cellular and molecular phenotypes.

genomics↗

bioRxiv2017

Cells With Treg-Specific FOXP3 Demethylation But Low CD25 Are Prevalent In Autoimmunity

Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3+ cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3+ cells within CD127lowCD25low CD4+ T cells (here defined as CD25lowFOXP3+ T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes. We show that CD25lowFOXP3+ T cells share phenotypic features resembling conventional CD127lowCD25highFOXP3+ Tregs, including demethylation of the Treg-specific epigenetic control region in FOXP3 that is highly enriched in HELIOS+ cells, and lack of IL-2 production. As compared to conventional Tregs, more CD25lowFOXP3+HELIOS+ T cells are in cell cycle (33.0% vs 20.7% Ki-67+; P = 1.3 x 10-9) and express the late-stage inhibitory receptor PD-1 (67.2% vs 35.5%; P = 4.0 x 10-18), while having reduced expression of the early-stage inhibitory receptor CTLA-4, as well as other Treg markers, such as FOXP3 and CD15s. The number of CD25lowFOXP3+ T cells are highly correlated (P = 1.2 x 10-19) with the proportion of CD25highFOXP3+ T cells in cell cycle (Ki-67+). These findings suggest that CD25lowFOXP3+ T cells represent a subset of Tregs that are derived from CD25highFOXP3+ T cells, and are a peripheral marker of recent Treg expansion in response to an autoimmune reaction in tissues.\n\nHighlights- FOXP3+ compartment within CD127lowCD25low T cells is expanded in autoimmune patients.\n\n- Increased numbers of CD25lowFOXP3+ T cells are a circulating marker of autoimmunity.\n\n- CD25lowFOXP3+ HELIOS+ T cells are fully demethylated at the FOXP3 TSDR.\n\n- CD25lowFOXP3+ T cells could represent a terminal stage of regulatory T cells.

immunology↗

bioRxiv2017

A rare IL2RA haplotype identifies SNP rs61839660 as causal for autoimmunity

IL2RA is associated with multiple autoimmune diseases including type 1 diabetes (T1D). Higher expression of IL2RA mRNA and its protein product CD25 in T lymphocytes is associated with a T1D-protective haplotype. Here we show that a rare variation of this haplotype that loses the protective allele at a single SNP, rs61839660, reduces IL2RA expression and T1D protection, identifying it as the causal factor in disease.

genetics↗

bioRxiv2017

Chromosome contacts in activated T cells identify autoimmune disease-candidate genes

BackgroundAutoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4+ T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes.\n\nResultsWithin four hours, activation of CD4+ T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C. By integrating promoter capture Hi-C data with genetic associations for five autoimmune diseases we prioritised 245 candidate genes with a median distance from peak signal to prioritised gene of 153 kb. Just under half (108/245) prioritised genes related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach.\n\nConclusionsOur systematic experimental framework offers an alternative approach to candidate causal gene identification for variants with cell state-specific functional effects, with achievable sample sizes.

genomics↗