Biology subjects

Turner, J.

Publications and source records attributed to Turner, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Stage-specific checkpoint signalling by ATM, ATR and DNA-PK safeguards oocyte genome integrity

In somatic cells, DNA double-strand breaks (DSBs) are potentially catastrophic lesions that activate phosphatidylinositol 3-kinase-related kinase (PIKK) signalling to promote DNA repair or eliminate damaged cells. During meiosis, however, DSBs are deliberately generated as essential intermediates in homologous recombination, raising the question of how DNA damage signalling distinguishes programmed recombination from genome instability. To define how PIKK signalling is adapted to these distinct contexts, we resolved the function of the three PIKKs ATM, ATR and DNA-PK in physiological meiotic recombination and the response to postnatal DNA damage in mouse oocytes. Following postnatal irradiation, ATM functions as the dominant response kinase, with ATR and DNA-PK acting redundantly to eliminate damaged oocytes. In contrast, meiotic surveillance is mediated by ATR, with ATR removal rescuing oocyte loss in response to asynapsis and, independently, to persistent meiotic DSBs. Our findings demonstrate that DNA damage signalling is developmentally reconfigured during oogenesis and highlight distinct pathways of oocyte elimination that may ultimately inform strategies to maintain the ovarian reserve in mammals.

molecular biology↗

bioRxiv2025

Chart Builder: An Interactive Tool for User Driven Data Visualization in the Electron Microscopy Data Bank

The cryogenic sample-electron microscopy (cryoEM) field has generated significant amounts of 3D Electron Microscopy (3DEM) volumetric data and associated metadata, now comprehensively archived in the Electron Microscopy Data Bank (EMDB - www.emdatabank.org) and the Electron Microscopy Public Image Archive (EMPIAR - www.empiar.org). Harnessing the full potential of these resources requires robust, flexible, and publicly accessible tools for data exploration, analysis and retrieval. Here, we present Chart Builder, an interactive web-based platform that enables researchers to create customizable, publication-quality visualizations directly from archival metadata, validation assessments, and cross-reference annotations. Chart Builder integrates the same query-driven and flexible Solr search system as EMDB search, into a user interface with tools to assist users to filter, group, and compare data without programming expertise. It supports multiple chart types (including line, bar, area, scatter (2D and 3D), histogram, bubble, pie, geographic and Venn diagrams) with customizable axes, data series, and statistical operators. Users can apply global filters, define temporal, categorical, or custom query-based axes, and explore multi-dimensional relationships interactively. Chart data-points are linked to their underlying datasets, such that visualisation interaction opens entry-level or archive-level search results for inspection and datasets from charts may be exported in several ways. Findability, accessibility, interoperability and reusability of data are facilitated by these direct access and export mechanisms, including HTML embedding, persistent URL sharing and chart/data download options. By combining interactivity and ease of use with up-to-date access to the EMDB and EMPIAR archive metadata, both computational and experimental communities may explore and visualize current metadata and export to formats for further analysis or as publication-ready figures. Chart Builder promotes community-driven data analysis and empowers users to evaluate trends in the biological 3DEM field. Chart Builder is freely accessible and fully integrated into the EMDB website at https://www.ebi.ac.uk/emdb/statistics/builder/.

biophysics↗

bioRxiv2025

JAG2-related muscular dystrophy and Notch signaling dysfunction in muscle stem cells

We previously identified a muscular dystrophy caused by biallelic variants in JAG2, whose protein product Jagged2 is a canonical Notch ligand. However, the disease mechanism remains unclear, particularly with respect to muscle stem cell (MuSC) function and muscle regeneration. We examined the consequences of JAG2 deficiency and modeled pathogenic JAG2 variants in vitro and in vivo, the latter in mouse and fly models and with particular attention to the MuSC-muscle endothelial cell (MuEC) niche. We found that both Jag2 deficiency and overexpression of pathogenic JAG2 variants impaired Notch signaling and myogenic self-renewal and differentiation. Hypomorphic Jag2 mutant (Jag2sm) mice display depleted MuSCs, corresponding with impaired muscle regeneration in those mice. Co-culture experiments and the examination of cell-type-specific Jag2 conditional knockout mice demonstrated that MuEC-specific Jag2 knockout resulted in reduced MuSC self-renewal, while MuSC-specific Jag2 knockout resulted in reduced myogenic differentiation. Human reference JAG2, but not human pathogenic variants of JAG2, rescued the deficiency of Serrate (Ser), the Drosophila ortholog of JAG2. Therefore, pathogenic variants in JAG2 impair muscle development and regeneration through disrupted cell-autonomous cis- inhibition and non-autonomous trans-activation involving Notch signaling dysfunction. Our findings indicate that optimizing JAG2-mediated Notch signaling is a potential therapeutic approach for JAG2-related muscular dystrophy.

developmental biology↗

bioRxiv2025

Non-obese genetic type 2 diabetes causes brain and behavioral hallmarks of chronic stress

The comorbidity of obesity, type 2 diabetes (T2D), and psychiatric disorders-- particularly anxiety and depression--is well documented. However, it remains unclear whether T2D, independently of obesity, contributes to the development of emotional dysfunctions. Furthermore, alterations in the hypothalamic-pituitary-adrenal (HPA) stress axis are commonly associated with both T2D and depression, but the role of stress in emotional disorders linked to T2D has been poorly explored. This study aimed to investigate the impact of T2D, independent of obesity, on the neuroendocrine stress axis, as well as molecular, cellular, and behavioral indicators of emotional dysfunction. Using the non-obese Goto-Kakizaki (GK) rat model of T2D, we assessed the effects of diabetes on hormonal and neuronal stress responses, molecular and structural markers of stress in the brain, and anxiety- and depressive-like behaviors. We also evaluated the impact of adrenalectomy in GK rats to determine the contribution of glucocorticoids to their behavioral impairments. Our findings reveal that non-obese diabetes leads to heightened endocrine and brain responses to stress, along with upregulation of stress-related molecular markers and structural features indicative of chronic stress, particularly in the medial prefrontal cortex. Additionally, GK rats exhibited pronounced anxiety- and depressive-like behaviors. Importantly, lowering glucocorticoid levels in GK rats helped alleviate some of the metabolic and emotional disturbances. This study suggests that T2D, independent of obesity, induces stress-related brain and behavioral changes, partly mediated by glucocorticoids. HighlightsO_LIT2D disrupts endocrine and neural responses to stress. C_LIO_LIT2D alters stress-related gene expression in the medial prefrontal cortex. C_LIO_LIT2D induces structural changes in the medial prefrontal cortex. C_LIO_LIT2D contributes to anxiety- and depressive-like behaviors. C_LIO_LIReducing corticosterone levels mitigates anxiety-like behavior in diabetic rats. C_LI

neuroscience↗

bioRxiv2025

A human induced pluripotent stem cell toolbox for studying sex chromosome effects

Sex chromosomes shape male (XY) - female (XX) differences in development and disease. These differences can be modelled in vitro by comparing XY and XX human induced pluripotent stem cells (hiPSCs). However, in this system, inter-individual autosomal variation and unstable X-dosage compensation can confound identification of sex chromosomal effects. Here, we utilise sex chromosome loss in XXY fibroblasts to generate XX and XY hiPSCs that are autosomally isogenic and exhibit stable X-dosage compensation. We also create X-monosomic (XO) hiPSCs, to investigate X-Y dosage effects. Using these autosomally isogenic lines, we examine sex differences in pluripotent stem cell expression. Transcriptional differences between XX and XY hiPSCs are surprisingly modest. However, X-haploinsufficiency induces transcriptional deregulation predominantly affecting autosomes. This effect is mediated by Y-genes with broad housekeeping functions that have X-homologues escaping X-inactivation. Our isogenic hiPSC lines provide a resource for exploring sex chromosome effects on development and disease in vitro.

genetics↗

bioRxiv2024

Evidence for white matter intrinsic connectivity networks at rest and during a task: a large-scale study and templates

Understanding white matter (WM) functional connectivity is crucial for unraveling brain function and dysfunction. In this study, we present a novel WM intrinsic connectivity network (ICN) template derived from over 100,000 fMRI scans, identifying 97 robust WM ICNs using spatially constrained independent component analysis (scICA). This WM template, combined with a previously identified gray matter (GM) ICN template from the same dataset, was applied to analyze a resting-state fMRI (rs-fMRI) dataset from the Bipolar-Schizophrenia Network on Intermediate Phenotypes 2 (BSNIP2; 590 subjects) and a task-based fMRI dataset from the MIND Clinical Imaging Consortium (MCIC; 75 subjects). Our analysis highlights distinct spatial maps for WM and GM ICNs, with WM ICNs showing higher frequency profiles. Modular structure within WM ICNs and interactions between WM and GM modules were identified. Task-based fMRI revealed event-related BOLD signals in WM ICNs, particularly within the corticospinal tract, lateralized to finger movement. Notable differences in static functional network connectivity (sFNC) matrices were observed between controls (HC) and schizophrenia (SZ) subjects in both WM and GM networks. This open-source WM NeuroMark template and automated pipeline offer a powerful tool for advancing WM connectivity research across diverse datasets.

neuroscience↗

bioRxiv2024

Defining a highly conserved B cell epitope in the receptor binding motif of SARS-CoV-2 spike glycoprotein

SARS-CoV-2 mRNA vaccines induce robust and persistent germinal centre (GC) B cell responses in humans. It remains unclear how the continuous evolution of the virus impacts the breadth of the induced GC B cell response. Using ultrasound-guided fine needle aspiration, we examined draining lymph nodes of nine healthy adults following bivalent booster immunization. We show that 77.8% of the B cell clones in the GC expressed as representative monoclonal antibodies recognized the spike protein, with a third (37.8%) of these targeting the receptor binding domain (RBD). Strikingly, only one RBD-targeting mAb, mAb-52, neutralized all tested SARS- CoV-2 strains, including the recent KP.2 variant. mAb-52 utilizes the IGHV3-66 public clonotype, protects hamsters challenged against the EG.5.1 variant and targets the class I/II RBD epitope, closely mimicking the binding footprint of ACE2. Finally, we show that the remarkable breadth of mAb-52 is due to the somatic hypermutations accumulated within vaccine-induced GC reaction. One Sentence SummaryBooster SARS-CoV-2 mRNA vaccine recruits and broadens GC B cell responses targeting a highly conserved site on receptor binding domain of spike glycoprotein.

immunology↗

bioRxiv2024

Executive dysfunction is associated with altered hippocampal-prefrontal functional connectivity in male 3xTg Alzheimer's model mice

Executive function depends on connectivity between the ventral hippocampus and medial prefrontal cortex (mPFC). How abnormalities in this pathway lead to cognitive dysfunction in Alzheimers disease (AD) have yet to be elucidated. Here, male 3xTg AD mice at 6-months displayed maladaptive decision-making in the rodent 4-Choice Gambling Task measure of executive function. Extracellular field recordings in the infralimbic cortex at this age showed layer-specific reductions in response amplitude and paired-pulse ratio following activation of hippocampal input fibres, indicating changes to short-term hippocampal-prefrontal synaptic plasticity. Bulk RNA sequencing of the mPFC in 6-month-old mice identified differential gene expression changes associated with calcium ion transport, glutamatergic, GABAergic, and dopaminergic neurotransmission. Seven of these genes (Gpm6b, Slc38a5, Ccr5, Kcnj10, Ddah1, Gad1, Slc17a8) were also differentially expressed in 3-month mice. These results reveal a pre-clinical deficit in executive function correlating with synaptic plasticity and gene expression changes in the mPFC of male 3xTg mice.

neuroscience↗

bioRxiv2024

Exploring the Phaeosphere: characterizing the microbiomes of Phaeocystis antarctica colonies from the coastal Southern Ocean and laboratory culture

Interactions between phytoplankton and bacteria play critical roles in shaping marine ecosystems. However, the intricate relationships within these communities--particularly in extreme and rapidly changing environments like the coastal Southern Ocean--remain poorly understood. Here, we apply targeted methods to directly characterize the microbiomes of individual colonies of Phaeocystis antarctica, a keystone phytoplankton species in the Southern Ocean, for the first time. We show that colony microbiomes are consistent in distinct geographic locations at approximately the same time, but shift significantly after a year of laboratory culture. The bacterial orders Alteromonadales, Oceanospirillales, and Sphingomonadales dominated the microbiomes of all field-collected colonies, whereas Caulobacterales, Cellvibrionales, and Rhodobacterales dominated colony microbiomes after culturing. Notably, the most abundant genera in field-collected colony microbiomes, the psychrophiles Paraglaciecola and Colwellia, were lost in culture. The shift in microbiome structure emphasizes the importance of field-based studies to capture the complexity of microbial interactions, especially for species from polar environments that are difficult to replicate in laboratory conditions. Furthermore, the relative abundances of bacterial taxa comprising the majority of field-collected colony microbiomes--e.g., Paraglaciecola sp. (Alteromonadales) and Nitrincolaceae (Oceanospirillales)--were strongly associated with Phaeocystis abundance in surface waters, highlighting their potential roles in bloom dynamics and carbon cycling. This research provides valuable insights into the ecological significance of prokaryotic interactions with a key phytoplankton species and underscores the necessity of considering these dynamics in the context of climate-driven shifts in marine ecosystems.

microbiology↗

bioRxiv2024

Cellular heterogeneity in hypertrophic burn scars in response to carbon dioxide laser therapy

Fractional carbon dioxide (AFCO2) laser therapy is used for treating pathological scarring, but the clinical outcomes are variable and the mechanisms of scar reduction poorly understood. We investigated the mechanisms underpinning efficacy of AFCO2 laser therapy, performing single-cell RNA sequencing in skin biopsies from patients with hypertrophic scars after AFCO2 laser therapy. Patients with younger scars (Good Responder, GR, <6 years from healing) had better scar reduction than patients with older scars (Poor Responder, PR, >6 years from healing) by various measures of scarring. scRNAseq analysis revealed that genes enriched in GR were associated with extracellular matrix and structure organisation (COL14A1, POSTN, SPARC); whereas genes enriched in PR were related to enhanced immune responses (IL-12, MSTN, HLA-DQA). The groups had distinct intercellular communication networks and differentiation trajectories after AFCO2, with regenerative Mesenchymal fibroblasts associated with a good response and inflammatory Secretory Papillary and Inflammatory Fibroblasts with a poor response.

cell biology↗

bioRxiv2024

In vivo tracking of ex vivo generated 89Zr-oxine labeled plasma cells by PET in a non-human primate model

B cells are an attractive platform for engineering to produce protein-based biologics absent in genetic disorders, and potentially for the treatment of metabolic diseases and cancer. As part of pre-clinical development of B cell medicines, we demonstrate a method to collect, ex vivo expand, differentiate, radioactively label, and track adoptively transferred non-human primate (NHP) B cells. These cells underwent 10- to 15-fold expansion, initiated IgG class switching, and differentiated into antibody secreting cells. Zirconium-89-oxine labeled cells were infused into autologous donors without any preconditioning and tracked by PET/CT imaging. Within 24 hours of infusion, 20% of the initial dose homed to the bone marrow and spleen and distributed stably and equally between the two. Interestingly, approximately half of the dose homed to the liver. Image analysis of the bone marrow demonstrated inhomogeneous distribution of the cells. The subjects experienced no clinically significant side effects or laboratory abnormalities. A second infusion of B cells into one of the subjects resulted in an almost identical distribution of cells, suggesting a non-limiting engraftment niche and feasibility of repeated infusions. This work supports the NHP as a valuable model to assess the potential of B cell medicines as potential treatment for human diseases.

bioengineering↗

bioRxiv2024

Effects of HMGCR deficiency on skeletal muscle development

Pathogenic variants in HMGCR were recently linked to a limb-girdle muscular dystrophy (LGMD) phenotype. The protein product HMG CoA reductase (HMGCR) catalyzes a key component of the cholesterol synthesis pathway. The two other muscle diseases associated with HMGCR, statin-associated myopathy (SAM) and autoimmune anti-HMGCR myopathy, are not inherited in a Mendelian pattern. The mechanism linking pathogenic variants in HMGCR with skeletal muscle dysfunction is unclear. We knocked down Hmgcr in mouse skeletal myoblasts, knocked down hmgcr in Drosophila, and expressed three pathogenic HMGCR variants (c.1327C>T, p.Arg443Trp; c.1522_1524delTCT, p.Ser508del; and c.1621G>A, p.Ala541Thr) in Hmgcr knockdown mouse myoblasts. Hmgcr deficiency was associated with decreased proliferation, increased apoptosis, and impaired myotube fusion. Transcriptome sequencing of Hmgcr knockdown versus control myoblasts revealed differential expression involving mitochondrial function, with corresponding differences in cellular oxygen consumption rates. Both ubiquitous and muscle-specific knockdown of hmgcr in Drosophila led to lethality. Overexpression of reference HMGCR cDNA rescued myotube fusion in knockdown cells, whereas overexpression of the pathogenic variants of HMGCR cDNA did not. These results suggest that the three HMGCR-related muscle diseases share disease mechanisms related to skeletal muscle development.

developmental biology↗

bioRxiv2024

Repeat modules and N-linked glycans define structure and antigenicity of a critical enterotoxigenic E. coli adhesin

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of cases of infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, in children, as well as human volunteers challenged with ETEC, diarrheal severity is significantly increased severity in blood group A (bgA) individuals. EtpA, is a secreted glycoprotein adhesin that functions as a blood group A lectin to promote critical interactions between ETEC and blood group A glycans on intestinal epithelia for effective bacterial adhesion and toxin delivery. EtpA is highly immunogenic resulting in robust antibody responses following natural infection and experimental challenge of human volunteers with ETEC. To understand how EtpA directs ETEC-blood group A interactions and stimulates adaptive immunity, we mutated EtpA, mapped its glycosylation by mass-spectrometry (MS), isolated polyclonal (pAbs) and monoclonal antibodies (mAbs) from vaccinated mice and ETEC-infected human volunteers, and determined structures of antibody-EtpA complexes by cryo-electron microscopy. Both bgA and mAbs that inhibited EtpA-bgA interactions and ETEC adhesion, bound to the C-terminal repeat domain highlighting this region as crucial for ETEC pathogen-host interaction. MS analysis uncovered extensive and heterogeneous N-linked glycosylation of EtpA and cryo-EM structures revealed that mAbs directly engage these unique glycan containing epitopes. Finally, electron microscopy-based polyclonal epitope mapping revealed antibodies targeting numerous distinct epitopes on N and C-terminal domains, suggesting that EtpA vaccination generates responses against neutralizing and decoy regions of the molecule. Collectively, we anticipate that these data will inform our general understanding of pathogen-host glycan interactions and adaptive immunity relevant to rational vaccine subunit design. Author summaryEnterotoxigenic E. coli (ETEC), a leading cause of diarrhea disproportionately affecting young children in low-income regions, are a priority for vaccine development. Individuals possessing A blood-type are more susceptible to severe cholera-like disease. EtpA, a secreted, immunogenic, blood group A binding protein, is a current vaccine target antigen. Here, we determined the atomic structure of EtpA in complex with protective as well as non-protective monoclonal antibodies targeting two different domains of the protein, allowing us to pinpoint key regions involved in blood-group A antigen recognition and uncover the mechanism of antibody-based protection. In addition, we show through mass-spectrometry that EtpA is extensively and heterogeneously glycosylated at surface-exposed asparagine residues by a promiscuous and low-fidelity glycosyltransferase, EtpC, and that this unique form of bacterial glycosylation is critical for to development of protective immune responses. Lastly, polyclonal antibodies from vaccinated mice as well as monoclonal antibodies obtained from ETEC-infected human volunteers revealed that the highly antigenic surface of EtpA exhibits both protective and non-protective epitopes. These results greatly expand our understanding of ETEC pathogenesis, and the immune responses elicited by these common infections, providing valuable information to aid in the rational design and testing of subunit vaccines.

microbiology↗

bioRxiv2024

Impact of the elderly lung mucosa on Mycobacterium tuberculosis metabolic adaptation during infection of alveolar epithelial cells

BackgroundTuberculosis (TB) is one of the top leading causes of death due to a single infectious agent. Upon infection, Mycobacterium tuberculosis (M.tb) is deposited in the alveoli and encounters the lung mucosa or alveolar lining fluid (ALF). We previously determined that increased M.tb replication in human macrophages and alveolar epithelial cells (ATs) is mediated by age-associated changes in human ALF. Here we determine the transcriptional profile of M.tb when exposed to healthy ALF from adult (A-ALF) or elderly (E-ALF) individuals before and during infection of ATs. ResultsPrior to infection, exposure to E-ALF upregulates M.tb genes associated with the ESX-4 secretion system, immunomodulatory proteins from the ESX-5 system, and genes encoding phospholipases, phosphatases, and proteases. During infection, E-ALF exposure upregulates key M.tb genes from the ESX-5 secretion system, genes associated with PDIMs biosynthesis and transport, and genes linked to bacterial oxidative stress defense mechanisms. ConclusionsThese findings demonstrate how altered ALF in old age can impact the metabolic status of M.tb, enabling greater adaptation to the host and potentially explaining Mtbs increased survival within host cells. Importantly, we present the first transcriptomic analysis on the impact of the elderly lung mucosa on M.tb pathogenesis during intracellular replication in ATs.

microbiology↗

bioRxiv2024

Mitochondrial Transplantation promotes protective effector and memory CD4+ T cell response during Mycobacterium tuberculosis infection and diminishes exhaustion and senescence in elderly CD4+ T cells

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (M.tb), remains a significant health concern worldwide, especially in populations with weakened or compromised immune systems, such as the elderly. Proper adaptive immune function, particularly a CD4+ T cell response, is central to host immunity against M.tb. Chronic infections, such as M.tb, as well as aging promote T cell exhaustion and senescence, which can impair immune control and promote progression to TB disease. Mitochondrial dysfunction contributes to T cell dysfunction, both in aging and chronic infections and diseases. Mitochondrial perturbations can disrupt cellular metabolism, enhance oxidative stress, and impair T-cell signaling and effector functions. This study examined the impact of mitochondrial transplantation (mito-transfer) on CD4+ T cell differentiation and function using aged mouse models and human CD4+ T cells from elderly individuals. Our study revealed that mito-transfer in naive CD4+ T cells promoted the generation of protective effector and memory CD4+ T cells during M.tb infection in mice. Further, mito-transfer enhanced the function of elderly human T cells by increasing their mitochondrial mass and modulating cytokine production, which in turn reduced exhaustion and senescence cell markers. Our results suggest that mito-transfer could be a novel strategy to reestablish aged CD4+ T cell function, potentially improving immune responses in the elderly and chronic TB patients, with a broader implication for other diseases where mitochondrial dysfunction is linked to T cell exhaustion and senescence.

immunology↗

bioRxiv2024

Drivers of Bird Communities in an Urban Neighborhood Vary by Scale

Given the accelerated pace of global biodiversity loss and rapid urbanization, it is becoming increasingly urgent to identify ways to minimize the costs and maximize the benefits of urban environments for wild flora and fauna. For instance, it has been estimated that 48% of all bird species are experiencing population declines. One of the main drivers of these declines is habitat loss and degradation associated with urbanization. Increased urbanization necessitates a better understanding of how to conserve birds in urban areas. Although relationships between urbanization and bird communities have been explored extensively, few studies have been conducted in residential neighborhoods, and the influence of urban environmental conditions, particularly air pollution, on bird communities remains unclear. In this study, we examined relationships between bird community metrics and environmental measures related to vegetation and air pollution within a residential neighborhood at multiple spatial scales. We found that bird species richness and the average number of native species were positively related to greenness (as measured by the normalized difference vegetation index; NDVI) within 50 m, and negatively associated with ambient levels of NO2 at 200 m. Similarly, we found the Hill-Shannon diversity index was positively associated with canopy cover, but negatively associated with NO2 at 200 m. The average number of invasive bird species, however, was negatively correlated with canopy cover at 50 m. The average number of native birds was negatively related to ultrafine particle (<100 nm in diameter) concentration. Unlike native bird abundances, invasive bird abundances were not sensitive to NO2 or ultrafine particles. Thus, our research suggests that reductions in air pollution, in combination with greening efforts that increase NDVI and canopy cover via the restoration of vegetation within urban neighborhoods, are likely to increase bird diversity and the abundances of native birds while reducing the abundance of invasive birds.

ecology↗

bioRxiv2023

Cross-species imputation and comparison of single-cell transcriptomic profiles

Cross-species comparison and prediction of gene expression profiles are important to understand regulatory changes during evolution and to transfer knowledge learned from model organisms to humans. Single-cell RNA-seq (scRNA-seq) profiles enable us to capture gene expression profiles with respect to variations among individual cells; however, cross-species comparison of scRNA-seq profiles is challenging because of data sparsity, batch effects, and the lack of one-to-one cell matching across species. Moreover, single-cell profiles are challenging to obtain in certain biological contexts, limiting the scope of hypothesis generation. Here we developed Icebear, a neural network framework that decomposes single-cell measurements into factors representing cell identity, species, and batch factors. Icebear enables accurate prediction of single-cell gene expression profiles across species, thereby providing high-resolution cell type and disease profiles in under-characterized contexts. Icebear also facilitates direct cross-species comparison of single-cell expression profiles for conserved genes that are located on the X chromosome in eutherian mammals but on autosomes in chicken. This comparison, for the first time, revealed evolutionary and diverse adaptations of X-chromosome upregulation in mammals.

bioinformatics↗

bioRxiv2023

EMDB - The Electron Microscopy Data Bank

The Electron Microscopy Data Bank (EMDB) is the archive of three-dimensional electron microscopy (3DEM) maps of biological specimens. As of 2021, EMDB has been managed by the Worldwide Protein Data Bank (wwPDB) as a wwPDB Core Archive. Today, the EMDB houses over 29,000 entries with maps containing cells, organelles, viruses, complexes and macromolecules. Herein, we provide an overview of the rapidly growing EMDB archive, including its current holdings, recent updates, and future plans.

bioinformatics↗