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Zhang, W.

Publications and source records attributed to Zhang, W..

At least 433 records · Page 24Linked to original sources

Repeat and haplotype aware error correction in nanopore sequencing reads with DeChat

Error self-correction is a pivotal first step in the analysis of long-read sequencing data. However, most existing methods for this purpose are primarily tailored for noisy sequencing data with error rates exceeding 5%, often collapsing true variants in repeats and haplotypes. Alternatively, some methods are heavily optimized for PacBio HiFi reads, leaving a gap in methods specifically designed for Nanopore R10 reads basecalled with high accuracy or super accuracy models, which typically have error rates below 2%. Here, we introduce DeChat, a novel approach specifically designed for Nanopore R10 reads. DeChat enables repeat- and haplotype-aware error correction, leveraging the strengths of both de Bruijn graphs and variant-aware multiple sequence alignment to create a synergistic approach. This approach avoids read overcorrection, ensuring that variants in repeats and haplotypes are preserved while sequencing errors are accurately corrected. Benchmarking experiments reveal that reads corrected using DeChat exhibit substantially fewer errors, ranging from several times to two orders of magnitude lower, compared to the current state-of-the-art approaches. Furthermore, the application of DeChat for error correction significantly improves genome assembly across various aspects. DeChat is implemented as a highly efficient, standalone, and user-friendly software and is publicly available at https://github.com/LuoGroup2023/DeChat.

bioinformatics↗

Contraction-induced endocardial id2b plays a dual role in regulating myocardial contractility and valve formation

Biomechanical cues play an essential role in sculpting organ formation. Comprehending how cardiac cells perceive and respond to biomechanical forces is a biological process with significant medical implications that remains poorly understood. Here we show that biomechanical forces activate endocardial id2b (inhibitor of DNA binding 2b) expression, thereby promoting cardiac contractility and valve formation. Taking advantage of the unique strengths of zebrafish, particularly the viability of embryos lacking heartbeats, we systematically compared the transcriptomes of hearts with impaired contractility to those of control hearts. This comparison identified id2b as a gene sensitive to blood flow. By generating a knockin reporter line, our results unveiled the presence of id2b in the endocardium, and its expression is sensitive to both pharmacological and genetic perturbations of contraction. Furthermore, id2b loss-of-function resulted in progressive heart malformation and early lethality. Combining RNA-seq analysis, electrophysiology, calcium imaging, and echocardiography, we discovered profound impairment in atrioventricular (AV) valve formation and defective excitation-contraction coupling in id2b mutants. Mechanistically, deletion of id2b reduced AV endocardial cell proliferation and led to a progressive increase in retrograde blood flow. In the myocardium, id2b directly interacted with the bHLH component tcf3b (transcription factor 3b) to restrict its activity. Inactivating id2b unleashed its inhibition on tcf3b, resulted in enhanced repressor activity of tcf3b, which subsequently suppressed the expression of nrg1 (neuregulin 1), an essential mitogen for heart development. Overall, our findings identify id2b as an endocardial cell-specific, biomechanical signaling-sensitive gene, which mediates intercellular communications between endocardium and myocardium to sculpt heart morphogenesis and function.

developmental biology↗

Chronic fluoxetine treatment desensitizes serotoninergic inhibition of GABA inputs and the intrinsic excitability of dorsal raphe serotonin neurons

Dorsal raphe serotonin (5-hydroxytryptamine, 5-HT) neurons are spontaneously active and release 5-HT that is critical to normal brain function such mood and emotion. Serotonin reuptake inhibitors (SSRIs) increase the synaptic and extracellular 5-HT level and are effective in treating depression. Treatment of two weeks or longer is often required for SSRIs to exert clinical benefits. The cellular mechanism underlying this delay was not fully understood. Here we show that the GABAergic inputs inhibit the spike firing of raphe 5-HT neurons; this GABAergic regulation was reduced by 5-HT, which was prevented by G-protein-activated inwardly rectifying potassium (Girk) channel inhibitor tertiapin-Q, indicating a contribution of 5-HT activation of Girk channels in GABAergic presynaptic axon terminals. Equally important, after 14 days of treatment of fluoxetine, a widely used SSRI type antidepressant, this 5-HT inhibition of GABAergic inputs was substantially downregulated. Furthermore, the chronic fluoxetine treatment substantially downregulated the 5-HT activation of the inhibitory Girk current in 5-HT neurons. Taken together, our results suggest that chronic fluoxetine administration, by blocking 5-HT reuptake and hence increasing the extracellular 5-HT level, can downregulate the function of 5-HT1B receptors on the GABAergic afferent axon terminals synapsing onto 5-HT neurons, allowing extrinsic, behaviorally important GABA neurons to more effectively influence 5-HT neurons; simultaneously, chronic fluoxetine treatment also downregulate somatic 5-HT autoreceptor-activated Girk channel-mediated hyperpolarization and decrease in input resistance and intrinsic excitability, rendering 5-HT neurons resistant to autoinhibition and leading to increased 5-HT neuron activity, potentially contributing to the antidepressant effect of SSRIs.

neuroscience↗

Singular Odorant Receptor Expression Orchestrated by Promoter Activation Specificity in Apis Mellifera Olfactory Sensory Neurons

Honeybee, positioned as an outgroup of flies and mosquitos, have exhibited intriguing duplications and expansions of OR genes in genomic studies. However, little is known about how the OR genes are expressed and regulated in honeybee olfactory sensory neurons (OSNs). In this study, we utilized a single-cell multi-omics approach to profile the transcriptome and chromatin accessibility in Apis mellifera antennal nuclei, aiming to elucidate OR gene expression and its underlying regulatory mechanisms. Our systematical analysis unveiled a similar singular expression pattern of ligand-specific receptors in Apis mellifera OSNs, parallel with those observed in Drosophila melanogaster. Mechanistically, we discovered that promoter activation of OR genes orchestrates receptor expression patterns. For instance, although multiple adjacent OR genes are co-expressed with a single active promoter through polycistronic transcription, only the first OR gene could produce functional receptor protein, as supported by transcriptome quantification in OSNs. Additionally, we found that co-expression of receptor proteins might occur only when co-expressed OR genes possess multiple accessible promoters. This scenario is less common than expected, considering the number and evolutionary age of OR genes in Apis mellifera, suggesting a selection favoring the specialization of rapidly expanded OR genes in Apis mellifera. Overall, our study provides significant insights into the insect olfaction system and the regulatory mechanisms of OR genes expression.

neuroscience↗

Peripheral B Lymphocyte Serves as A Reservoir for The Persistently Covert Infection of Mandarinfish Siniperca chuatsi Ranavirus

Genus Ranavirus in family Iridoviridae is composed of large members with various genomic sizes and viral gene contents, infecting a variety of ectothermic vertebrates including reptile, amphibians and bony fish worldwide. Mandarinfish ranavirus (MRV) is a very distinctive member among genus Ranavirus. Persistently convert infection of MRV were previously observed in natural outbreak of MRV, but the underlying mechanism remains unclear. We here evidenced that mandarinfish peripheral B lymphocytes are implemented as viral reservoirs to maintain persistent and covert infection. When mandarinfish were infected with sublethal dosage of MRV under nonpermissive temperature (19 {o}C) and permissive temperature (26 {o}C), respectively, all fish in 19 {o}C group survived and entered persistent phase of infection characterized with very low viral load in white blood cell, whereas partial fish died of MRV infection in 26 {o}C group, and the survivals then initiated persistent status. Gradually raising temperature, vaccination and dexamethasone treatment can reactivate the quiescent MRV to replicate and result in partial mortality. The viral reservoir investigates showed that IgM+-labelled B lymphocytes but not CD3{Delta}+-labelled T lymphocytes and MRC-1+-labelled macrophages are target cells for the persistent infection of MRV. Moreover, the quiescent MRV could not be reactivated by heat-killed Escherichia coli, indicating a very different reactivation mechanism from that of other known rannaviral member. Collectively, we are the first to confirm the presence of B cell-dependent persistent and covert infection of ranavirus, and provide a new clue for better understanding the complex infection mechanism of vertebrate iridovirus, especially regarding ranavirus. IMPORTANCEViruses known as HIV, HBV and EBV etc. evade host immune clearance by establishing long-term even lifelong persistent or latent infection. In vertebrate iridovirus, FV3, the type species of genus Ranavirus was evidenced to establish persistent infection by using Xenopus peritoneal macrophages as reservoirs. MRV is a very distinctive ranavirus from FV3 with very different genomic content and host species. We here uncovered MRV establishes persistent and covert infection by using peripheral B lymphocytes as virus reservoirs. During persistent infection, very low copies of quiescent MRV were harbored in peripheral B lymphocytes. Water temperature stress, vaccination stimulation, and dexamethasone treatment can reactivate quiescent MRV to replicate in abundance via a non-TLR5-mediated manner, and results in recurrence of MRV disease. Our finding suggests the diversity and complexity of the pathogenic mechanisms among ranaviruses, and also has important scientific significance for in-depth understanding of the infection and immunity interaction of vertebrate iridoviruses.

microbiology↗

NK Cell Exhaustion in Wilson's Disease Revealed by Single-cell RNA Sequencing Predicts the Prognosis of Cholecystitis

Metabolic abnormalities associated with liver disease have a significant impact on the risk and prognosis of cholecystitis. However, the underlying mechanism is complicated and remains to be elucidated. In particular, the effect of metabolic abnormalities on the progression of cholecystitis through the regulation of immune cell function is poorly understood. In this study, we investigated this issue using Wilsons disease (WD) as a model. Wilsons disease is a genetic disorder characterized by impaired mitochondrial function and abnormal copper metabolism. Our retrospective clinical study of over 600 patients with WD found that they have a significantly higher incidence of cholecystitis and a poorer prognosis. The immune cell landscape in the hepatic mesenchymal stromal microenvironment of WD patients was shown using single-cell RNA. A major change is the constitution and function of the innate immune system, including enhanced antigen presentation process, activation of the immune response, and activation of lymphocytes. The proportion of mononuclear phagocytes and natural killer (NK) cells is increased, and the primary characteristic and function of macrophage, Kupffer cell, neutrophil, and NK cell are altered. Exhaustion of NK cell is the fundamental factor, supported by an increase in the expression of the inhibitory receptors KLRC1 and TIGIT and a decrease in the expression of cytotoxic molecules. Clinical tissue and blood samples verified increased KLRC1+ and TIGIT+ NK cells and decreased IFN{gamma}+ NK cells in WD. Further bioinformatic analysis has confirmed a positive correlation between NK cell exhaustion and poor prognosis in cholecystitis and other inflammatory diseases. The study demonstrated abnormal function of liver mesenchymal immune cells triggered by specific metabolic dysfunction in WD, with a focus on the correlation between NK cell exhaustion and poor healing of cholecystitis. Our findings highlight the immune cell dysfunction due to metabolic changes in hepatocytes and provide new insights into the improvement of inflammatory diseases by assessing immune cell function.

immunology↗

Formation of multinucleated osteoclasts depends on an oxidized species of cell surface associated La protein

The bone-resorbing activity of osteoclasts plays a critical role in the life-long remodeling of our bones that is perturbed in many bone loss diseases. Multinucleated osteoclasts are formed by the fusion of precursor cells, and larger cells - generated by an increased number of cell fusion events - have higher resorptive activity. We find that osteoclast fusion and bone-resorption are promoted by reactive oxygen species (ROS) signaling and by an unconventional low molecular weight species of La protein, located at the osteoclast surface. Here, we develop the hypothesis that Las unique regulatory role in osteoclast multinucleation and function is controlled by a ROS switch in La trafficking. Using antibodies that recognize reduced or oxidized species of La, we find that differentiating osteoclasts enrich an oxidized species of La at the cell surface, which is distinct from the reduced La species conventionally localized within cell nuclei. ROS signaling triggers the shift from reduced to oxidized La species, its dephosphorylation and delivery to the surface of osteoclasts, where La promotes multinucleation and resorptive activity. Moreover, intracellular ROS signaling in differentiating osteoclasts oxidizes critical cysteine residues in the C-terminal half of La, producing this unconventional La species that promotes osteoclast fusion. Our findings suggest that redox signaling induces changes in the location and function of La and may represent a promising target for novel skeletal therapies.

cell biology↗

Glutamate (E299) is a key residue in the evolutionarily divergence of the SAM-dependent methyltransferases DnrK and RdmB in anthracycline biosynthesis

A novel sub-class of S-adenosyl-L-methionine (SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines, which include antineoplastic compounds. Intriguingly, the closely related methyltransferases DnrK and RdmB have markedly divergent functions. We investigated their catalytic activities and discovered a previously unknown 10-hydroxylation activity for DnrK and 4-O-methylation activity for RdmB. Isotope-labeling demonstrated that the 10-hydroxy group introduced by DnrK is derived from water molecules while RdmB utilizes O2. A single residue, E299, was the key modulator in the differing catalytic functions of DnrK and RdmB, especially the decarboxylative oxidation activity. Furthermore, the multifunctionality of DnrK was demonstrated to be SAM-tunable and concerted, whereas RdmB activity was cofactor-dependent and stepwise. Our findings expand the versatility and importance of methyltransferases and should aid studies to enrich the structural diversity and bioactivities of anthracyclines.

biochemistry↗

Engineered Ubiquitin Variants Mitigate Pathogenic Bacterial Ubiquitin Ligase Function

During infection some pathogenic gram-negative bacteria, such as Salmonella, manipulate the host ubiquitination system through the delivery of secreted effectors known as novel E3 ubiquitin ligases (NELs). Despite the presence of NELs amongst these well-studied bacterial species, their unique structure has limited the tools that are available to probe their molecular mechanisms and explore their therapeutic potential. In this work, we report the identification of two high affinity engineered ubiquitin variants that can modulate the activity of the Salmonella enterica serovar Typhimurium encoded NEL, SspH1. We show that these ubiquitin variants suppress SspH1-mediated toxicity phenotypes in Saccharomyces cerevisiae. Additionally, we provide microscopic and flow cytometric evidence that SspH1-mediated toxicity is caused by interference with S. cerevisiae cell cycle progression that can be suppressed in the presence of ubiquitin variants. In vitro ubiquitination assays revealed that these ubiquitin variants increased the amount of SspH1-mediated ubiquitin chain formation. Interestingly, despite the increase in ubiquitin chains, we observe a relative decrease in the formation of SspH1-mediated K48-linked ubiquitin chains on its substrate, PKN1. Taken together our findings suggest that SspH1 toxicity in S. cerevisiae occurs through cell cycle interference and that an engineered ubiquitin variant approach can be used to identify modulators of bacterially encoded ubiquitin ligases. Author SummaryNovel E3 ligases (NELs) are a family of secreted effectors found in various pathogenic gram- negative bacteria. During infection these effectors hijack vital host ubiquitin signaling pathways to aid bacterial invasion and persistence. Despite interacting with a protein as highly conserved as ubiquitin, they have a distinct architecture relative to the eukaryotic E3 enzymes. This unique architecture combined with the indispensable role ubiquitin signaling plays in host cell survival has made hindering the contribution of NELs to bacterial infections a difficult task. Here, we applied protein engineering technology to identify two ubiquitin variants (Ubvs) with high affinity for SspH1, a Salmonella-encoded NEL. We provide evidence that these high affinity Ubvs suppress a known SspH1-meidated toxicity phenotype in the eukaryotic model system Saccharomyces cerevisiae. We also show that this suppression occurs without interfering with host ubiquitin signaling. Furthermore, we demonstrate the ability of a Ubv to modulate the activity of SspH1 in vitro, ultimately altering the lysine linkages found in SspH1-mediated ubiquitination. To our knowledge, this is the first evidence that an engineered ubiquitin variant approach can be implemented to modulate the activity of a family of previously untargetable bacterial-encoded E3 ligases.

microbiology↗

Targeting IDH1-Mutated Oligodendroglioma with Acid Ceramidase Inhibitors

Oligodendroglioma is genetically defined as a tumor harboring isocitrate dehydrogenase 1 or 2 mutations (IDH1mut/IDH2mut) and 1p/19q co-deletions. Previously, we reported that in IDH1mut gliomas, D-2HG, the product of IDH1 mutant enzyme produces an increase in monounsaturated fatty acid levels that are incorporated into ceramides, tilting the S1P-to-ceramide rheostat toward apoptosis. Herein, we exploited this imbalance to further induce and IDHmut-specific glioma cell death. We report for the first time that the inhibition of acid ceramidase (AC) induces apoptosis and provides a benefit in mice survival in IDH1mut oligodendroglioma. We demonstrated an IDH1mut-specific cytotoxicity of SABRAC, an irreversible inhibitor of AC, in patient-derived oligodendroglioma cells. Exploring the mechanism of action of this drug, we found that SABRAC activates both extrinsic and intrinsic apoptosis in an ER stress-independent manner, pointing to a direct action of AC-related ceramides in mitochondria permeability. The activation of apoptosis detected under SABRAC treatment was associated with up to 30-fold increase in some ceramide levels and its derivatives from the salvage pathway. We propose that this novel enzyme, AC, has the potential to increase survival in oligodendroglioma with IDH1mut and should be considered in the future.

cancer biology↗

CA1i pyramidal neurons mediate the role of NMDA receptor subunit GluN3A in depressive behavior and D-serine anti-depression

The hippocampus is a highly complex structure, defined by profound structural, functional, and molecular heterogeneity. The GluN3A subunit, which forms non-classic N-methyl-D-aspartate receptors (NMDARs), is enriched in the hippocampal CA1 subregion and has a poorly understood functional role, especially in stress-related behavioral regulation. Here, we employed chronic social defeat stress (CSDS) and GluN3A knockout (KO) mouse models combined with behavioral, molecular, genetic, pharmacological, and circuit-level analyses to investigate the role of hippocampal GluN3A in stress coping. We found that CSDS selectively reduced GluN3A expression in the intermediate CA1 (CA1i) region. Decreased GluN3A expression in CA1i, from either stress or genetic deletion, promoted passive coping behaviors, whereas overexpression of GluN3A in CA1i reversed the phenotype under both conditions. Mechanistically, consistent with GluN3A enrichment in pyramidal neurons, c-fos staining and fiber photometry revealed that GluN3A was essential for CA1i pyramidal neuronal activation during coping behaviors. Further chemogenetic manipulations demonstrated that activating CA1i neurons facilitated active coping, while inhibition induced passivity. Moreover, local administration of D-serine, an agonist of GluN3A-containing NMDARs, rapidly shifted coping behavior from passive to active by activating CA1i neurons via GluN3A-dependent mechanisms. Circuit tracing revealed that CA1i neurons project to multiple sub-hippocampal and cortico-limbic regions, and GluN3A overexpression selectively enhanced downstream neuronal activity in CA3 and infralimbic cortex, but not in the nucleus accumbens. Together, these findings identify GluN3A as a key molecule linking hippocampal subregional specialization with adaptive stress coping, and suggest that the rapid, resilience-promoting effects of D-serine are also GluN3A-dependent.

neuroscience↗

Epithelial IL-2 is critical for NK cell-mediated cancer immunosurveillance in mammary glands

Interleukin 2 (IL-2) is the first identified cytokine and its interaction with receptors has been known to shape the immune responses in many lymphoid or non-lymphoid tissues for more than four decades. Active T cells are the primary cellular source for IL-2 production and epithelial cells have never been considered the major cellular source of IL-2 under physiological conditions. It is, however, tempting to speculate that epithelial cells could potentially express IL-2 that regulates the intricate interactions between epithelial cells and lymphocytes. Datamining our recently published single-cell RNAseq in the mouse mammary gland identified IL-2 expression in mammary epithelial cells, which is induced by prolactin via the STAT5 signaling pathway. Furthermore, epithelial IL-2 plays a crucial role in maintaining the physiological functions of natural killer (NK) cells within the mammary glands. IL-2 deletion in the mammary epithelial cells leads to a significant reduction in the number and function of NK cells, which in turn results in defective immunosurveillance, expansion of luminal epithelial cells, and tumor development. Interestingly, T cells in the mammary glands are not changed, indicating the specific regulation of NK cells by epithelial IL-2 production. In agreement, we also found that human epithelial cells express IL-2 and NK cells express the highest level of IL2RB among all the immune cells. Here, we provide the first evidence that epithelial cells produce IL-2, which is critical for maintaining the physiological functions of NK cells in immunosurveillance.

immunology↗

Premature thymic involution in young Foxn1lacz mutant mice causes peripheral T cell phenotypes similar to aging-induced immunosenescence

The thymus is a primary lymphoid organ generating self-restricted and self-tolerant naive T-cells. Early in life the thymus starts to involute, resulting in decreased naive T-cell output which may be more self-reactive, leading to an increased prevalence of autoimmunity. A decrease in the transcription factor FOXN1 is an early event in thymic involution. Using the Foxn1lacz model, we studied how premature thymic involution affects the thymic microenvironment, thymocytes, and peripheral T cell immunity. We found that early thymic involution led to aged-like thymic epithelial cells that resulted in aged-like thymocyte phenotypes, with a significant decrease in CD4+ single-positive T-cells. We also observed severe lymphopenia in Foxn1lacz mice caused by the premature decrease in T-cell production, resulting in a peripheral T-cell phenotype similar to de novo aged peripheral T-cells. Moreover, following T cell receptor stimulation, Foxn1lacz peripheral T cells had reduced IL-2 secretion and strong initial IFN-g responses, resembling aged wild-type peripheral T-cell responses. Lastly, influenza response in Foxn1lacz had a reduction in some aspects of T cell responses to influenza infection, similar to thymectomized mice. Our study shows an independent and direct impact of premature thymic involution on both thymopoiesis and peripheral immune niches likely contributing to immunosenescence and inflammaging as observed in the elderly population.

immunology↗

Targeting the sphingolipid rheostat in IDH1mut glioma alters cholesterol homeostasis and triggers apoptosis via membrane degradation

The cross-regulation of metabolism and trafficking is not well understood for the vital sphingolipids and cholesterol constituents of cellular compartments. While reports are starting to surface on how sphingolipids like sphingomyelin (SM) dysregulate cholesterol levels in different cellular compartments (Jiang et al., 2022), limited research is available on the mechanisms driving the relationship between sphingolipids and cholesterol homeostasis, or its biological implications. Previously, we have identified sphingolipid metabolism as a unique vulnerability for IDH1mut gliomas via a rational drug design. Herein, we show how modulating sphingolipid levels affects cholesterol homeostasis in brain tumors. However, we unexpectedly discovered for the first time that C17 sphingosine and NDMS addition to cancer cells alters cholesterol homeostasis by impacting its cellular synthesis, uptake, and efflux leading to a net decrease in cholesterol levels and inducing apoptosis. Our results reflect a reverse correlation between the levels of sphingosines, NDMS, and unesterified, free cholesterol in the cells. We show that increasing sphingosine and NDMS (a sphingosine analog) levels alter not only the trafficking of cholesterol between membranes but also the efflux and synthesis of cholesterol. We also demonstrate that despite the effort to remove free cholesterol by ABCA1-mediated efflux or by suppressing machinery for the influx (LDLR) and biosynthetic pathway (HMGCR), apoptosis is inevitable for IDH1mut glioma cells. This is the first study that shows how altering sphingosine levels directly affects cholesterol homeostasis in cancer cells and can be used to manipulate this relationship to induce apoptosis in IDH1mut gliomas.

cancer biology↗

SAMP: Identifying Antimicrobial Peptides by an Ensemble Learning Model Based on Proportionalized Split Amino Acid Composition

AbstractIt is projected that 10 million deaths could be attributed to drug-resistant bacteria infections in 2050. To address this concern, identifying new-generation antibiotics is an effective way. Antimicrobial peptides (AMPs), a class of innate immune effectors, have received significant attention for their capacity to eliminate drug-resistant pathogens, including viruses, bacteria, and fungi. Recent years have witnessed widespread applications of computational methods especially machine learning (ML) and deep learning (DL) for discovering AMPs. However, existing methods only use features including compositional, physiochemical, and structural properties of peptides, which cannot fully capture sequence information from AMPs. Here, we present SAMP, an ensemble random projection (RP) based computational model that leverages a new type of features called Proportionalized Split Amino Acid Composition (PSAAC) in addition to conventional sequence-based features for AMP prediction. With this new feature set, SAMP captures the residue patterns like sorting signals at around both the N-terminus and the C-terminus, while also retaining the sequence order information from the middle peptide fragments. Benchmarking tests on different balanced and imbalanced datasets demonstrate that SAMP consistently outperforms existing state-of-the-art methods, such as iAMPpred and AMPScanner V2, in terms of accuracy, MCC, G-measure and F1-score. In addition, by leveraging an ensemble RP architecture, SAMP is scalable to processing large-scale AMP identification with further performance improvement, compared to those models without RP. To facilitate the use of SAMP, we have developed a Python package freely available at https://github.com/wan-mlab/SAMP.

bioinformatics↗

ExpOmics: a comprehensive web platform empowering biologists with robust multi-omics data analysis capabilities

MotivationHigh-throughput technologies have yielded a broad spectrum of multi-omics datasets, offering unparalleled insights into complex biological systems. However, effectively analyzing this diverse array of data presents challenges, given factors such as species diversity, data types, costs, and limitations of available tools. ResultsWe propose ExpOmics, a comprehensive web platform featuring seven applications and four toolkits with 28 customizable analysis functions, spanning various aspects of differential expression, co-expression, WGCNA analysis, feature selection, and functional enrichment analysis. ExpOmics empowers users to effortlessly upload and explore multi-omics data without organism restriction, supporting a wide array of data types including gene, mRNA, lncRNA, miRNA, circRNA, piRNA, and protein expression data. It is compatible with diverse gene nomenclatures and expression value types. Moreover, ExpOmics enables users to comprehensive analysis of 22,427 transcriptomic datasets sourced from 63 projects and 196 cancer subtypes in TCGA, discovering cancer biomarkers and targets. The analysis results from ExpOmics are visually presented in high-quality graphical formats suitable for publication, available for free download. In summary, ExpOmics can serves as a robust platform for global researchers to delve into diverse expression datasets, gain biological insights, and formulate testable hypotheses. Availability and implementationExpOmics is available at http://www.biomedical-web.com/expomics.

bioinformatics↗

Microbiota from young mice counteracts susceptibility to age-related gout through modulating butyric acid levels in aged mice

Gout is a prevalent form of inflammatory arthritis that occurs due to high levels of uric acid in the blood leading to the formation of urate crystals in and around the joints, particularly affecting the elderly. Recent research has provided evidence of distinct differences in the gut microbiota of patients with gout and hyperuricemia when compared to healthy individuals. However, the link between gut microbiota and age-related gout remained underexplored. Our study found that gut microbiota plays a crucial role in determining susceptibility to age-related gout. Specifically, we observed that age-related gut microbiota regulated the activation of the NLRP3 inflammasome pathway and modulated uric acid metabolism. More scrutiny highlighted the positive impact of "younger" microbiota on the gut microbiota structure of old or aged mice, enhancing butanoate metabolism and butyric acid content. Experimentation with butyrate supplementation indicated that butyric acid exerts a dual effect, inhibiting inflammation in acute gout and reducing serum uric acid levels. These insights emphasize the potential of gut microbiome rejuvenation in mitigating senile gout, unraveling the intricate dynamics between microbiota, aging, and gout. It potentially serves as a therapeutic target for senile gout-related conditions.

microbiology↗

Bioinformatics Copilot 1.0: A Large Language Model-powered Software for the Analysis of Transcriptomic Data

The field of single-cell transcriptomics has been producing extensive datasets, advancing our understanding of cellular functions in various tissues, and empowering diagnosis, prognosis, and drug development. However, parsing through this data has been a monumental task, often stretching weeks to months. This bottleneck arises due to the sheer volume of data generated--ranging from hundreds of gigabytes to tens of terabytes--that demands extensive time for analysis. Moreover, the data analysis involves an intricate series of steps utilizing various software packages, creating a steep learning curve for biologists. Additionally, the iterative nature of data analysis in this domain necessitates a deep biological insight to formulate relevant questions, conduct analysis, interpret results, and refine hypotheses. This iterative loop has required close collaboration between biologists and bioinformaticians, which is hampered by protracted communication cycles. To address these challenges, we present a large language model-powered software, Bioinformatics Copilot 1.0. It allows users to analyze data through an intuitive natural language interface, without requiring proficiency in programming languages such as Python or R. It is engineered for cross-platform functionality, with support for Mac, Windows, and Linux. Importantly, it facilitates local data analysis, ensuring adherence to stringent data management regulations that govern the use of patient samples in medical and research institutions. We anticipate that this tool will expedite the data analysis workflow in numerous research endeavors, thereby accelerating advancements in the biomedical sciences.

bioinformatics↗