Biology subjects

Wang, C.

Publications and source records attributed to Wang, C..

At least 397 records · Page 22Linked to original sources

bioRxiv2024

TIRE-seq: an Integrated Sample Extraction and Transcriptomics Workflow for High Throughput Perturbation Studies

RNA sequencing (RNA-seq) is widely used in biomedical research, advancing our understanding of gene expression across biological systems. Traditional methods require upstream RNA extraction from biological inputs, adding time and expense to workflows. We developed TIRE-seq (Turbocapture Integrated RNA Expression Sequencing) to address these challenges. TIRE-seq integrates mRNA purification directly into library preparation, eliminating the need for a separate extraction step. This streamlined approach reduces turnaround time, minimizes sample loss, and improves data quality. A comparative study with the widely used Prime-seq protocol demonstrates TIRE-seqs superior sequencing efficiency with crude cell lysates as inputs. TIRE-seqs utility was demonstrated across three biological applications. It captured transcriptional changes in stimulated human T cells, revealing activation-associated gene expression profiles. It also identified key genes driving murine dendritic cell differentiation, providing insights into lineage commitment. Lastly, TIRE-seq analyzed the dose-response and time-course effects of temozolomide on patient-derived neurospheres, identifying differentially expressed genes and enriched pathways linked to the drugs mechanism of action. With its simplified workflow and high sequencing efficiency, TIRE-seq offers a cost-effective solution for large-scale gene expression studies across diverse biological systems.

genomics↗

bioRxiv2024

scCompass: An integrated cross-species scRNA-seq database for AI-ready

Emerging single-cell sequencing technology has generated large amounts of data, allowing analysis of cellular dynamics and gene regulation at the single-cell resolution. Advances in artificial intelligence enhance life sciences research by delivering critical insights and optimizing data analysis processes. However, inconsistent data processing quality and standards remain to be a major challenge. Here we propose scCompass, which provides a data quality solution to build a large-scale, cross-species and model-friendly single-cell data collection. By applying standardized data pre-processing, scCompass integrates and curates transcriptomic data from 13 species and nearly 105 million single cells. Using this extensive dataset, we are able to archieve stable expression genes (SEGs) and organ-specific expression genes (OSGs) in human and mouse. We provide different scalable datasets that can be easily adapted for AI model training and the pretrained checkpoints with state-of-the-art (SOTA) single-cell foundataion models. In summary, the AI-readiness of scCompass, which combined with user-friendly data sharing, visualization and online analysis, greatly simplifies data access and exploitation for researchers in single cell biology(http://www.bdbe.cn/kun).

bioinformatics↗

bioRxiv2024

Nanoparticle-Supported, Rapid, Digital Quantification of Neutralizing Antibodies Against SARS-CoV-2 Variants

The measurement of neutralizing immune responses to viral infection is essential, given the heterogeneity of human immunity and the emergence of new virus strains. However, neutralizing antibody (nAb) assays often require high-level biosafety containment, sophisticated instrumentation, and long detection times. Here, as a proof-of-principle, we designed a nanoparticle-supported, rapid, electronic detection (NasRED) assay to assess the neutralizing potency of monoclonal antibodies (mAbs) against SARS-CoV-2. The gold nanoparticles (AuNPs) coated with human angiotensin-converting enzyme 2 (ACE2) protein as nAb potency reporters were mixed with the mAbs to be tested, as well as streptavidin-conjugated multivalent spike (S) protein or their receptor binding domains (RBD). High-affinity and ACE2-competitive nAbs alter the S (or RBD)-to-ACE2 binding level and modulate AuNP cluster formation and precipitation. The amount of free-floating AuNP reporters is quantified by a semiconductor-based readout system that measures the AuNPs optical extinction, producing nAb signals that can differentiate SARS-CoV-2 variants (Wuhan-Hu-1, Gamma, and Omicron). The modular design nature, short assay time (less than 30 minutes), and portable and inexpensive readout system make this NasRED-nAb assay applicable to measuring vaccine potency, immune responses to infection, and the efficacy of antibody-based therapies.

immunology↗

bioRxiv2024

PM2.5 from Automobile Exhaust Induces Apoptosis in Male Rat Germ Cells via the ROS-UPRmt Signaling Pathway

ObjectiveTo explore the underlying mechanism behind the fine particulate matters (PM2.5)-mediated regulation of reproductive function in male rats, and to determine the role of vitamins in this process. MethodsIn all, 32 male SD rats were randomized to a control cohort (normal saline), a Vit cohort (vitamin C at 100 mg/kg + vitamin E at 50 mg/kg), a PM2.5 cohort (PM2.5 10 mg/kg), and a PM2.5+Vit cohort (PM2.5 exposure + vitamin C at 100 mg/kg + vitamin E at 50 mg/kg), with eight rats in each cohort. After four weeks of exposure, mating experiments were carried out. Thereafter, rats were euthanized, and the testis and epididymis tissues were excised for hematoxylin-eosin (HE) staining and sperm quality analysis. Apoptosis of testis tissues was quantified via a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the testicular oxidative stress (OS)-, apoptosis- and mitochondrial unfolded protein response (UPRmt)-related essential protein expressions were measured via western blotting (WB). ResultsAfter PM2.5 exposure, the sperm count and motility decreased, while sperm abnormality and the apoptosis index increased. HE staining showed that the number of spermatogenic cells decreased. WB showed that the PM2.5 group had decreased expressions of superoxide dismutase (SOD), nuclear factor E2-related factor 2 (Nrf2), and B-cell lymphoma-2 (Bcl-2) (p < 0.05), increased expressions of malondialdehyde (MDA), Bcl-2 associated X protein (Bax), and Caspase3 (p < 0.05), and downregulated expressions of C/EBP homologous protein (CHOP), heat shock protein 60 (HSP60), and activating transcription factor 5 (ATF5) (p < 0.05). These were all reversed by vitamin intervention. ConclusionPM2.5 from automobile exhaust disrupts male reproductive function. A combination of vitamins may protect reproductive function via the reactive oxygen species (ROS)-UPRmt signaling pathway. HighlightsO_LIPM2.5 from vehicle exhaust can cause apoptosis of male germ cells. C_LIO_LIPM2.5 from vehicle exhaust induces germ cell apoptosis through the ROS-UPRmt signaling pathway. C_LIO_LICombined vitamin C and E can enhance UPRmt activity to alleviate the germ cell apoptosis caused by PM2.5 from vehicle exhaust. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/621651v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@d3f5edorg.highwire.dtl.DTLVardef@1b6daa1org.highwire.dtl.DTLVardef@1cba0b4org.highwire.dtl.DTLVardef@1a3c9f1_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2024

Unanchored ubiquitin chains promote the non-canonical inflammasome via UBXN1

Ubiquitination is a major posttranslational covalent modification that regulates numerous cellular processes including inflammasome signaling. Cells also contain unanchored ubiquitin chains (polyUb) that bind protein targets non-covalently, but their physiological functions in immunity have been appreciated only recently. Here, we report that ubiquitin regulatory x domain-containing protein 1 (UBXN1) activates the noncanonical inflammasome via unanchored Lysin (K) 48- or 63-linked polyUb. UBXN1 deficiency impairs the activation of caspase-4/11, secretion of inflammasome-dependent cytokines and pyroptosis in response to intracellular lipopolysaccharide (LPS). UBXN1-deficient mice are protected from LPS- and cecal-ligation-and-puncture-induced sepsis, evidenced by reduced mortality and systemic inflammation, compared to UBXN1-sufficient littermates. Mechanistically, UBXN1 together with unanchored K48/63-linked polyUb bind caspase-4/11, the intracellular sensors of LPS, and promote their assembly and activation. Depleting cellular unanchored polyUb with recombinant ubiquitin-specific proteinase 5 (USP5) reduces UBXN1 binding to caspase-4/11 and inflammasome signaling, while USP5 inhibitors enhance pyroptosis in an UBXN1-dependent manner. Thus, this study identifies a critical UBXN1-dependent posttranslational mechanism involved in noncanonical inflammasome activation and UBXN1 as a potential therapeutic target for sepsis and advances a fundamental understanding of unanchored polyUb biology.

immunology↗

bioRxiv2024

Stratified analysis identifies HIF-2α as a therapeutic target for highly immune-infiltrated melanomas

While immune-checkpoint blockade (ICB) has revolutionized treatment of metastatic melanoma over the last decade, the identification of broadly applicable robust biomarkers has been challenging, driven in large part by the heterogeneity of ICB regimens and patient and tumor characteristics. To disentangle these features, we performed a standardized meta-analysis of eight cohorts of patients treated with anti-PD-1 (n=290), anti-CTLA-4 (n=175), and combination anti-PD-1/anti-CTLA-4 (n=51) with RNA sequencing of pre-treatment tumor and clinical annotations. Stratifying by immune-high vs -low tumors, we found that surprisingly, high immune infiltrate was a biomarker for response to combination ICB, but not anti-PD-1 alone. Additionally, hypoxia-related signatures were associated with non-response to anti-PD-1, but only amongst immune infiltrate-high melanomas. In a cohort of scRNA-seq of patients with metastatic melanoma, hypoxia also correlated with immunosuppression and changes in tumor-stromal communication in the tumor microenvironment (TME). Clinically actionable targets of hypoxia signaling were also uniquely expressed across different cell types. We focused on one such target, HIF-2, which was specifically upregulated in endothelial cells and fibroblasts but not in immune cells or tumor cells. HIF-2 inhibition, in combination with anti-PD-1, enhanced tumor growth control in pre-clinical models, but only in a more immune-infiltrated melanoma model. Our work demonstrates how careful stratification by clinical and molecular characteristics can be leveraged to derive meaningful biological insights and lead to the rational discovery of novel clinical targets for combination therapy.

cancer biology↗

bioRxiv2024

Dysregulation of locus-specific repetitive elements in TCGA pan-cancers

Understanding the role of repetitive elements (REs) in cancer development is crucial for identifying novel biomarkers and therapeutic targets. This study investigated the locus-specific dysregulation of REs, including differential expression and methylation of REs, across 12 TCGA cancer types stratified by their genomic context (i.e., genic and intergenic REs). We found uniquely dysregulated genic REs co-regulated with their corresponding transcripts and associated with distinct biological functions in different cancer types. Uniquely dysregulated intergenic REs were identified in each cancer type and used to cluster different sample types. Recurrently dysregulated REs were identified in several cancer types, with genes associated with up-regulated genic REs involved in cell cycle processes and those associated with down-regulated REs involved in the extracellular matrix. Interestingly, 4 out of 5 REs consistently down-regulated in all 12 cancer types were located in the intronic region of the TMEM252, a recently discovered tumor suppressor gene. TMEM252 expression was also down-regulated in 10 of 12 cancer types, suggesting its potential importance across a wide range of cancer types. With the corresponding DNA methylation array data, we found a higher prevalence of hypo-methylated REs in most cancer types (10 out of 12). Despite the slight overlaps between differentially expressed REs and differentially methylated REs, we showed that methylation of locus-specific REs negatively correlates with their expression in some cancer types.

bioinformatics↗

bioRxiv2024

In-Situ Structure and Topography of AMPA Receptor Scaffolding Complexes Visualized by CryoET

Most synapses in the brain transmit information by the presynaptic release of vesicular glutamate, driving postsynaptic depolarization through AMPA-type glutamate receptors (AMPARs). The nanometer-scale topography of synaptic AMPARs regulates response amplitude by controlling the number of receptors activated by synaptic vesicle fusion. The mechanisms controlling AMPAR topography and their interactions with postsynaptic scaffolding proteins are unclear, as is the spatial relationship between AMPARs and synaptic vesicles. Here, we used cryo-electron tomography to map the molecular topography of AMPARs and visualize their in-situ structure. Clustered AMPARs form structured complexes with postsynaptic scaffolding proteins resolved by sub-tomogram averaging. Sub-synaptic topography mapping reveals the presence of AMPAR nanoclusters with exclusion zones beneath synaptic vesicles. Our molecular-resolution maps visualize the predominant information transfer path in the nervous system.

neuroscience↗

bioRxiv2024

Citalopram exhibits immune-dependent anti-tumor effects by modulating C5aR1+ TAMs and CD8+ T cells

Administration of selective serotonin reuptake inhibitors (SSRIs) is associated with a reduced cancer risk and shows significant anti-tumor effects across multiple tumor types, suggesting the potential for repurposing SSRIs in cancer therapy. Nonetheless, the specific molecular target and mechanism of action of SSRIs remain to be fully elucidated. Here, we reveal that citalopram exerts an immune-dependent anti-tumor effects in hepatocellular carcinoma (HCC). Interestingly, the anti-HCC effects of citalopram are not reliant on its conventional target, the serotonin transporter. Through various drug repurposing approaches, including global reverse gene expression profiling, drug affinity responsive target stability assay, and molecular docking, the complement component 5a receptor 1 (C5aR1) is identified as a new target of citalopram. C5aR1 is predominantly expressed by tumor-associated macrophages (TAMs), and citalopram treatment enhances local macrophage phagocytosis and elicits CD8+ T anti-tumor immunity. C5aR1 deficiency or depletion of CD8+ T cells hinders the anti-HCC effects of citalopram. Collectively, our study reveals the immunomodulatory roles of citalopram in inducing anti-tumor immunity, and provides a basis for considering the repurposing of SSRIs as promising anticancer agents for HCC treatment.

cancer biology↗

bioRxiv2024

OfWRKY33 binds to the key linalool synthase gene OfTPS7 to promote linalool synthesis in Osmanthus fragrans flowers

Volatile aroma compounds make significant contributions to human perception of flowers. Osmanthus fragrans is a famous aroma plant and linalool along with its oxides are proved to be the dominant aroma active compounds. Although some terpene synthases (TPSs) have been characterized, a comprehensive study of the hub metabolic gene and its transcriptional regulation remain to be revealed. Here, we selected a specific cultivar Boyeyingui (BBYG) with the highest content of linalool among 20 wide-cultivated cultivars for genome and transcriptome sequencings. Among the 25 new putative OfTPSs, only OfTPS6, OfTPS7 could exclusively produce linalool in planta. Biochemical analysis demonstrated that OfTPS6, OfTPS7 were able to catalyze geranyl diphosphate (GPP) into linalool and a small proportion of other monoterpenes in vitro. Spatial and temporal correlation analysis further confirmed the transcript level of OfTPS7 was closely associated with linalool content in diverse cultivars and different tissues, suggesting OfTPS7 was the essential linalool synthase gene. Combined with yeast one-hybrid screen and weighted correlation network analysis (WGCNA), a nucleus-localized transcriptional factor OfWRKY33 was considered as a potential modulator. Y1H, dual-luciferase assay and electrophoretic mobility shift assay (EMSA) demonstrated that OfWRKY33 directly bound to the W-box of OfTPS7 promoter to stimulate its transcription. OfWRKY33 could coordinately induce the expressions of OfTPS7, 1-deoxy-d-xylulose 1 (OfDXS1), thereby promoting the linalool formation. The results first revealed the hub linalool synthase gene OfTPS7 and a novel TF participating in the complex transcriptional regulation of linalool biosynthesis in O. fragrans flowers.

biochemistry↗

bioRxiv2024

m6A-mediated epi-transcriptomic dysregulation underlies synaptic dysfunction in fragile X syndrome

Fragile X syndrome (FXS), the leading genetic cause of intellectual disability, arises from FMR1 gene silencing and loss of the FMRP protein. N6-methyladenosine (m6A) is a prevalent mRNA modification essential for post-transcriptional regulation. FMRP is known to bind to and regulate the stability of m6A-containing transcripts. However, how loss of FMRP impacts on transcriptome-wide m6A modifications in FXS patients remains unknown. To answer this question, we generated cortical neurons differentiated from induced pluripotent stem cells (iPSC) derived from healthy subjects and FXS patients. In electrophysiology recordings, we validated that synaptic and neuronal network defects in iPSC-derived FXS neurons corresponded to the clinical EEG data of the patients from which the corresponding iPSC line was derived. In analysis of transcriptome-wide methylation, we show that FMRP deficiency led to increased translation of m6A writers, resulting in hypermethylation that primarily affecting synapse-associated transcripts and increased mRNA decay. Conversely, in the presence of an m6A writer inhibitor, synaptic defects in FXS neurons were rescued. Taken together, our findings uncover that an FMRP-dependent epi-transcriptomic mechanism contributes to FXS pathogenesis by disrupting m6A modifications in FXS, suggesting a promising avenue for m6A- targeted therapies.

neuroscience↗

bioRxiv2024

Reshaping the tumor microenvironment by degrading glycoimmune checkpoints Siglec-7 and -9

Cancer treatment has been rapidly transformed by the development of immune checkpoint inhibitors targeting CTLA-4 and PD-1/PD-L1. However, many patients fail to respond, especially those with an immunosuppressive tumor microenvironment (TME), suggesting the existence of additional immune checkpoints that act through orthogonal mechanisms. Sialic acid-binding immunoglobulin-like lectin (Siglec)-7 and -9 are newly designated glycoimmune checkpoints that are abundantly expressed by tumor-infiltrating myeloid cells. We discovered that T cells express only basal levels of Siglec transcripts; instead, they acquire Siglec-7 and -9 from interacting myeloid cells in the TME via trogocytosis, which impairs their activation and effector function. Mechanistically, Siglec-7 and -9 suppress T cell activity by dephosphorylating T cell receptor (TCR)-related signaling cascades. Using sulfur fluoride exchange (SuFEx) click chemistry, we developed a ligand that binds to Siglec-7 and -9 with high-affinity and exclusive specificity. Using this ligand, we constructed a Siglec-7/9 degrader that targets membrane Siglec-7 and -9 to the lysosome for degradation. Administration of this degrader induced efficient Siglec degradation in both T cells and myeloid cells in the TME. We found that Siglec-7/9 degradation has a negligible effect on macrophage phagocytosis, but significantly enhances T cell anti-tumor immunity. The degrader, particularly when combined with anti-CTLA-4, enhanced macrophage antigen presentation, reshaped the TME, and resulted in long-lasting T cell memory and excellent tumor control in multiple murine tumor models. These findings underscore the need to consider exogenous checkpoints acquired by T cells in the TME when selecting specific checkpoint blockade therapy to enhance T cell immunity.

immunology↗

bioRxiv2024

LPS binding caspase activation and recruitment domains (CARDs) are bipartite lipid binding modules

Caspase-11 is an innate immune pattern recognition receptor (PRR) that detects cytosolic bacterial lipopolysaccharides (LPS) through its caspase activation and recruitment domain (CARD), triggering inflammatory cell death known as pyroptosis. Caspase-11 also detects eukaryotic (i.e. self) lipids. This observation raises the question of whether common or distinct mechanisms govern the interactions with self and nonself lipids. In this study, using biochemical, computational, and cell-based assays, we report that the caspase-11 CARD functions as a bipartite lipid-binding module. Distinct regions within the CARD bind to phosphate groups and long acyl chains of self and nonself lipids. Self-lipid binding capability is conserved across numerous caspase-11 homologs and orthologs. The symmetry in self and nonself lipid detection mechanisms enabled us to engineer an LPS-binding domain de novo, using an ancestral CARD-like domain present in the fish Amphilophus citrinellus. These findings offer critical insights into the molecular basis of LPS recognition by caspase-11 and highlight the fundamental and likely inseparable relationship between self and nonself discrimination.

immunology↗

bioRxiv2024

Neural mechanisms of the transition from planning to execution in speech production

Speaking is the primary way that humans communicate. This communication is enabled by a production system that can plan and execute unique combinations of speech sounds. Although a distributed network of brain regions has been implicated in speaking, it is unclear how planning and execution of speech are coordinated to produce meaningful sounds. Leveraging the high spatio-temporal resolution of intracranial recordings at different spatial scales, we show distinct neural mechanisms that facilitate speech planning and execution. During planning, different levels of speech units are coded discretely at distinct prefrontal sites. These planned units are then dynamically integrated at various cortical levels to guide subsequent execution. During speech execution, speech motor regions generate continuous sequences that reflect both discrete speech sound units and their transitional properties between units. This rapid neural transition from discrete speech units to motor sequences links speech planning with execution and enables our effortless ability to speak.

neuroscience↗

bioRxiv2024

Gene encoding CC-NBS-LRR protein on rye chromosome 1RS confers wheat stripe rust resistance

Stripe rust, a globally widespread disease, stands as one of the most significant threats to wheat cultivation. The 1BL/1RS translocation, renowned for its robust resistance to both rust and powdery mildew, has historically played an important role in wheat breeding and production. The gene for resistance to stripe rust on the 1RS is known as Yr9 and plays an important role in the production of wheat, but over the course of long-term breeding had lost its resistance due to the evolution of stripe rust towards greater and greater virulence. In this paper, we cloned the stripe rust resistance gene, Yr9, from triticale by genetic mapping approach. The Yr9 encodes a typical nucleotide-binding leucine-rich repeat (NLR) protein. Both transgenic and overexpression of Yr9 in highly stripe rust susceptible wheat varieties conferred complete resistance to the stripe rust races CYR17 and partial resistance to the stripe rust races CYR32, CYR33, and CYR34. In addition, the Yr9 allele in the 1BL/1RS translocation line also showed the same level of resistance to stripe rust. Both two alleles loses resistance when deployed in the field or inoculated with mixed physiological races collected from the field. Our findings provide valuable insights for breeders to strategically incorporate disease resistance genes and provides a foundation for further understanding how pathogenic bacteria might evolve to evade recognition via NLR type proteins. SignificanceThe 1BL/1RS translocation between wheat and rye is the most successful case of exogenous gene application in plant genetic improvement and has been used in wheat breeding for over 50 years. Here we report the cloning of a stripe rust resistance gene Yr9 located on rye chromosome 1RS using a triticale population. The Yr9 encodes a coiled-coil nucleotide-binding site leucine-rich repeat (CC-NBS-LRR) protein that show complete resistance to the stripe rust races CYR17 and partial resistance to the stripe rust races CYR32, CYR33, and CYR34, albeit demonstrating susceptibility under field conditions. Our findings position Yr9 as an ideal candidate gene to study the mechanism of inactivation of disease resistance genes as a result of pathogen evolution.

genetics↗

bioRxiv2024

Analyzing the Molecular Mechanism of Eucalyptol, Limonene and Pinene Enteric Capsules (QIENUO) in the Treatment of Pulmonary cystic fibrosis with Network Pharmacology and Verifying Molecular Docking

ObjectiveTo explore the mechanism of Eucalyptol, Limonene and Pinene Enteric Capsules (QIENUO) in the treatment of pulmonary cystic fibrosis (CPF), analyze the common targets of QIENUO and CPF, and verify the molecular docking of core proteins and small molecules. MethodsThe main active compounds and their corresponding targets were obtained from PubChem, SwissTargetprediction, GeneCards, PharmMapper and TCMSP databases. Targets related to CPF were screened from GeneCards, OMIM, DisGeNET and TTD databases. The common "QIENUO-CPF" targets were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) through the website of Weishengxin. Protein-protein interaction (PPI) network and compound-target-pathway network were constructed by Cytoscape, and the network parameters were systematically analyzed. The interaction between core protein and monomer components was evaluated and verified by molecular docking method. Results228 active compounds target and 1354 CPF-related targets were screened out, and 92 common targets were analyzed by GO and KEGG. The results showed that the therapeutic effect of QIENUO on CPF was mainly through AMPK signaling pathway, cGMP-PKG signaling pathway and TGF-{beta} signaling pathway. The results of molecular docking show that the binding energy of 9 of 15 pairs of ligand-receptor pairs is lower than-6 kjmol-1. ConclusionQIENUO exhibits huge potential as a therapeutic agent for the treatment of pulmonary cystic fibrosis. The specific molecular mechanism and effective active components of QIENUO treat CPF were studied and demonstrated, which provided theoretical basis for better clinical application of QIENUO.

bioinformatics↗

bioRxiv2024

scGNN+: Adapting ChatGPT for Seamless Tutorial and Code Optimization

Foundation models have transformed AI by leveraging large-scale data to efficiently perform diverse tasks, and their applications in bioinformatics are primarily focused on data-centric tasks like cell type annotation and gene expression analysis. However, their potential extends beyond data analysis, offering significant opportunities in software development and optimization, such as code refinement, tutorial generation, and advanced visualization. For example, models like OpenAI Codex can suggest optimized code snippets and generate well-documented, reproducible workflows, enhancing accessibility and reducing computational complexity. Despite these advantages, the use of foundation models for improving computational tool engineering in single-cell research remains underutilized. To address this gap, we developed scGNN+, a web-based platform that combines the power of graph neural networks with the capabilities of ChatGPT to enhance reproducibility, code optimization, and visualization. scGNN+ further simplifies the process for users by generating standardized, well-annotated code, making complex procedures more accessible to non-programmers. Additionally, ChatGPT integration allows users to create high-quality, customizable visualizations through natural language prompts, improving data interpretation and presentation. Ultimately, scGNN+ offers a user-friendly, reproducible, and optimized solution for single-cell research, leveraging the full potential of foundation models in bioinformatics. scGNN+ is publicly available at https://bmblx.bmi.osumc.edu/scgnn+.

bioinformatics↗

bioRxiv2024

Association analysis of PAEP, KRT10 and BMP7 Genes SNPs with reproductive traits in Kele pigs

The aims of this study were to investigate the effects of single nucleotide polymorphisms (SNPs) in progestogen-associated endometrial protein (PAEP), keratin 10 (KRT10), and bone morphogenetic protein 7 (BMP7) genes on reproductive traits (total number of piglets born, number of piglets born alive, litter birth weight, number of piglets weaned and litter weight weaned) in Kele pigs. We used a total of 255 multiparous Kele sow (2-4 parities) as research materials. SNPs were identified by PCR amplification instrument and sequence alignment software DANMAN. The population genetic characteristics of SNPs were analyzed using the SHEsis online software. Bioinformatics analysis of SNPs were conducted using RNAfold, SOPMA, SWISS-MODEL, and Swiss-PdbViewer programs. The associations between the SNPs and reproductive traits in Kele pigs were analyzed through SPSS 22.0 software. In this study, nine SNPs were identified in the three genes: g.1884992 T>C (exon 4), g.1885152 G>C (intron 4) and g.1887834 G>A (intron 4) in PAEP, g.21643703 C>T (intron 4), g.21643714 G>A (intron 4) and g.21643741 G>A (exon 5) in KRT10, and g.57647887 G>A (intron 3), g.57647990 C>T (intron 3) and g.57648145 C>G (intron 3) in BMP7. In SNPs g.1884992 T>C of PAEP, missense mutation eventuated structural changes in mRNA and proteins secondary structure. In SNPs g.21643741 G>A of KRT10, synonymous mutation led to alteration in mRNA secondary structure. For PAEP, the CC genotype in SNPs g.1885152 G>C and the AA genotype in SNPs g.1887834 G>A showed significantly higher values than other genotypes in all reproduction traits except for litter birth weight, preliminarily identified as favorable genotypes. For KRT10, the GG genotype in SNPs g.21648641 G>A showed significant superiority than AA genotype (P<0.05) in all aspects except for litter birth weight, and notably surpassed the GA genotype in total number of piglets born (P<0.05), preliminarily recognized as a favorable genotype. Regarding BMP7, the GA genotype in SNPs g.57647887 G>A and the CT genotype in SNPs g.57647990 C>T exhibited significantly higher number of piglets born alive and number of piglets born alive compared to other genotypes (P<0.05). And the GG genotype in SNPs g.57648145 C>G was significantly associated with higher litter birth weight (P<0.05). The result of diplotype analyses indicated that the H3H3 (CCGGGG) of PAEP and H3H3 (CCGGAA) of KRT10 had a significant effect on the five traits. For BMP7, the H4H4 (AATTGG) diplotype showed a significant influence on all genotypes except litter birth weight.

genetics↗