Biology subjects

Cao, C.

Publications and source records attributed to Cao, C..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Sub-Nanomolar Detection and Discrimination of Microcystin Congeners Using Aerolysin Nanopores

Climate-driven disruptions in aquatic ecosystems are amplifying cyanotoxin production, threatening drinking and recreational water safety. Monitoring of these toxins is challenged by requirements of the low {micro}g/L detections limits and structural diversity. Here, we employ aerolysin nanopores to distinguish seven of the most prevalent microcystin congeners, both individually and in mixtures, at environmentally relevant concentrations. Importantly, we showed that aerolysin enables the detection of microcystins in different lake water samples at concentrations below the World Health Organizations intervention thresholds, reaching picomolar sensitivity. Moreover, combining experiments and molecular dynamics simulations, we further investigated the microcystin sensing mechanism, suggesting that the ionic current blockage is primarily governed by K238 in aerolysin, while dwell time is regulated by R220 constriction site. Our results open the way to use the nanopore sensing technology for real-time monitoring of microcystins in drinking water sources and surface waters.

bioengineering↗

bioRxiv2025

Locust cGAS-like receptors recognize derivatives of a Gypsy retrotransposon to synergize with RNAi against viral invasion

The co-option of transposable elements (TEs) as immune sentinels represents an evolutionarily conserved strategy across metazoans, yet the molecular mechanisms linking retrotransposon reactivation to antiviral defense remain enigmatic. Here, we identify LmGypsy, a long terminal repeat (LTR) retrotransposon in Locusta migratoria, as a critical mediator of biphasic antiviral immunity against Acrididae reovirus (ARV). ARV infection triggers selective de-repression of LmGypsy, which orchestrates dual antiviral pathways: (1) its encoded reverse transcriptase synthesizes viral DNA (vDNA) from ARV RNA, fueling RNA interference (RNAi)-mediated viral RNA degradation through Dicer-2-dependent vsiRNA biogenesis; (2) LmGypsy-derived nucleic acids activate cGAS-like receptors (LmcGASs) and induce immune responses. Strikingly, vDNA persists in infected locusts from 24 h post-infection until host death, suggesting a role in sustaining antiviral activity akin to immune memory mechanisms observed in Diptera. This study provides the first evidence that insect cGAS homologs function as retrotransposon sensors, mirroring mammalian cGAS-STING recognition of endogenous retroviral elements. Our findings redefine retrotransposons as central hubs in arthropod antiviral immunity, bridging RNAi and nucleic acid-sensing pathways to establish a coordinated defense network. These results illuminate conserved principles of TE-immune crosstalk and highlight LmGypsy as a paradigm for understanding host-transposon coevolution in antiviral contexts.

immunology↗

bioRxiv2025

A photostable genetically encoded voltage indicator for imaging neural activities in tissue and live animals

Genetically encoded voltage indicators (GEVIs) enable noninvasive, high-speed monitoring of electrical activity but are constrained by limited brightness and rapid photobleaching under continuous illumination. Here, we present Vega, a highly photostable green fluorescence GEVI with both high sensitivity ({Delta}F/F = -33% per 100 mV) and fast response (1.34 ms). Under one-photon excitation at 1 W/cm2, Vega exhibits more than 20-fold slower photobleaching than the spectrally similar GEVI, Ace-mNeon2. In acute mouse brain slice, Vega enabled wide-field high-fidelity recording of action potentials from 51 neurons simultaneously. In pancreatic islets, it revealed heterogeneous {beta}-cell activation and intercellular coupling in response to glucose elevation. Finally, one-photon imaging in awake mice demonstrated stable cortical voltage mapping in vivo. Vega thus overcomes the longstanding photostability-performance trade-off, enabling chronic, high-fidelity voltage imaging across preparations.

bioengineering↗

bioRxiv2025

Mechanism-driven screening of membrane-targeting and pore-forming antimicrobial peptides

The rise of antibiotic resistance has generated an urgent demand for the discovery of new antimicrobial peptides (AMPs), prompting the development of various screening strategies. However, the specific function mechanisms of AMPs are often overlooked during the screening and optimization processes. In this study, we introduce a mechanism-driven screening approach that employs machine learning-based computational models to identify peptide sequences that target membranes and form pores. This approach explicitly considers critical factors such as structural features, membrane ainity, and the ability of peptides to oligomerize. Our method was applied to the metaproteomes of poison frogs, African clawed frogs, and human skin, followed by experimental validation. Seven peptides were successfully screened, each demonstrating antimicrobial activity with minimal hemolysis and cytotoxicity. These peptides exhibited membrane disruption capabilities in liposome leakage assays, with three showing broad-spectrum antimicrobial activity. Furthermore, single-molecule experiments indicated that these peptides can oligomerize on membranes, while electrophysiological measurements detected pore formation, confirming the effectiveness of our screening strategy. Therefore, our screening approach can effectively identify AMP sequences that act through membrane-targeting and poreforming mechanisms, offering a promising, mechanism-driven strategy for the discovery of new antimicrobial agents to combat antibiotic resistance.

biophysics↗

bioRxiv2025

Neoadjuvant anti-4-1BB confers protection against spontaneous metastasis through low-affinity intratumor CD8+ T cells in triple-negative breast cancer

Neoadjuvant immunotherapy seeks to harness the primary tumor as a source of relevant tumor antigens to enhance systemic anti-tumor immunity through improved immunological surveillance. Despite having revolutionized the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC), a significant portion of patients remain unresponsive and succumb to metastatic recurrence post-treatment. Here, we found that optimally scheduled neoadjuvant administration of anti-4-1BB monotherapy was able to counteract metastases and prolong survival following surgical resection. Phenotypic and transcriptional profiling revealed enhanced 4-1BB expression on tumor-infiltrating intermediate (Tint), relative to progenitor (Tprog) and terminally exhausted (Tterm) T cells. Furthermore, Tint was enriched in low-affinity T cells. Treatment with anti-4-1BB drove clonal expansion of Tint, with reduced expression of tissue-retention marker CD103 in Tprog. This was accompanied by increased TCR clonotype sharing between paired tumors and pre-metastatic lungs. Further interrogation of sorted intratumor T cells confirmed enhanced T cell egress into circulation following anti-4-1BB treatment. In addition, gene signature extracted from anti-4-1BB treated Tint was consistently associated with improved clinical outcomes in BRCA patients. Combinatorial neoadjuvant anti-4-1BB and ablation of tumor-derived CXCL16 resulted in enhanced therapeutic effect. These findings illustrate the intratumor changes underpinning the efficacy of neoadjuvant anti-4-1BB, highlighting the reciprocity between local tissue-retention and distant immunologic fortification, suggesting treatment can reverse the siphoning of intratumor T cells to primary tumor, enabling redistribution to distant tissues and subsequent protection against metastases.

immunology↗

bioRxiv2025

Charge-based fingerprinting of unlabeled full-length proteins using an aerolysin nanopore

Proteins play essential roles in cellular processes and are involved in numerous diseases, driving the need for efficient proteoform identification. While nanopore technology was highly successful for DNA sequencing, this approach has not yet delivered its full potential in protein identification. Here, we demonstrate the capabilities of an aerolysin nanopore for direct identification of a range of unlabeled full-length proteins. Combining low pH and guanidinium chloride, we generate a strong electroosmotic flow that enables an efficient capture and translocation, resulting in distinct fingerprints from single-protein translocations. Using machine learning classifier, we achieve 80% accuracy in distinguishing seven related proteins with 38%-70% pairwise sequence identities. Differences in fingerprints largely reflect the distribution of positive charges in the protein sequences, providing a rational basis for the observed sensitivity. With further development, fingerprint-predictions could allow to infer de novo protein sequence information from single-molecule data, offering a powerful tool for proteomics.

bioengineering↗

bioRxiv2024

A Prediction Method of Land Use Type Evolution Based on Long and Short-Term Memory Networks--Taking Gansu Province as an Example

In the context of escalating global climate change and human activities, understanding the driving mechanisms behind land use change and predicting future trends is crucial. This study takes Gansu Province as a case, using land use type data from 1990 to 2020 to construct a Long Short-Term Memory (LSTM) model to predict land use changes over the next decade (2021-2030). The results indicate that land use types in Gansu Province exhibit significant dynamic changes, with forest area continuously increasing, built-up land rapidly expanding, and areas of unused land and grassland significantly decreasing. These changes reflect the combined effects of ecological protection policies, urbanization, and land development. The models predictions suggest that built-up land has absorbed substantial areas of unused land, grassland, and cultivated land, with accelerated urbanization. Forest area growth is attributed to the implementation of ecological restoration policies, while grassland and water areas show fluctuating changes, and the area of unused land continues to decrease. The findings not only provide data support for land resource management and ecological protection, but also offer scientific evidence for the formulation of sustainable land use policies, which can serve as an important reference for the sustainable use and management of land resources in Gansu Province and similar regions.

bioengineering↗

bioRxiv2024

Genome-wide investigation of outer membrane protein families under mosaic evolution in Escherichia coli

Several genes in Gram-negative bacteria encoding outer membrane proteins (OMPs) have been reported to show patterns of mosaic evolution featured by mixture of negative selection and local recombination. Here, we proposed a strategy, and applied it to screen OMPs under mosaic evolution in Escherichia coli in the genome level. In total, 21 OMP families, including 16 new ones, were detected with the typical patterns of mosaic evolution. An abosolute majority of the protein families are conserved in E. coli for the composition, genomic loci and the overall structures. Highly Variable Regions (HVRs) can be recognized, which are frequently located extracellularly within the protruding loops. There are only limited number of major HVR sequence types, within which positively selected sites can be detected ocassionally. Based on the simulated results of multiple models, the OMPs under mosaic evolution are often with good antigenicity, with HVRs of various sequence types coinciding with the B-cell epitopes of the strongest immunogenicity. The study futher broadened our understanding of the characteristics of mosaic evolution and the functions of OMPs in Gram-negative bacteria, laying an important foundation for their potential translational applications. ImportanceIt is important to understand the evolutionary mechanisms of bacterial OMP-encoding genes, which would facilitate the development of anti-bacterial reagents. This study made the first genome-wide screening of bacterial OMPs under mosaic evolution, and increased the list of candidate OMP families by 3 folds in E. coli, far more than we expected. The study further confirmed the hypothesis about the evolutionary, micro-evolutionary and structural features of these OMPs, and facilitated the functional theory of mosaic evolution. Moreover, the findings of limited HVR sequence types and strong immunogenicity of HVRs paved important foundation for application of these OMPs and their HVRs in development of antibodies or other anti-bacterial treatment.

microbiology↗

bioRxiv2024

NLGN3 contributes to angiogenesis in myocardial infarction via activation of the Gαi1/3-Akt Pathway

BACKGROUNDAngiogenesis is an important repair mechanism for myocardial infarction. Neuroligin-3 (NLGN3) can promote angiogenesis by activating Gi1/3-Akt signaling following ischemic brain injury. This study investigated the role of NLGN3 in myocardial infarction (MI). METHODS AND RESULTSOn the 7th day after MI, the plasma level of NLGN3 in patients was significantly higher than in the control group. A mouse model of MI also showed significantly increased expression of NLGN3 in heart tissue. Single-nucleus transcriptome analysis revealed that NLGN3 was located predominantly in cardiac fibroblasts and endothelial cells (ECs). Endothelial-specific knockdown of NLGN3, or inhibition of NLGN3 using ADAM10i, significantly increased the ischemic area, reduced angiogenesis, and worsened cardiac function. Co-immunoprecipitation (Co-IP) experiments showed that NLGN3 interacted with Gi1/3. The Gi1/3 knockout (Gi1/3-KO) mouse model of MI showed an increased ischemic area, decreased angiogenesis, and impaired cardiac function. Mechanistic studies showed that the NLGN3-Gi1/3 signaling pathway exerts cardioprotective effects by promoting EC proliferation and tube formation through the PI3K-Akt-mTOR pathway. Silencing of Gi1/3 largely eliminated the ability of NLGN3-promoting cardiac ECs to proliferate and form tubes. CONCLUSIONOur findings suggest the endothelial NLGN3-Gi1/3 signaling pathway promotes angiogenesis and reduces the ischemic area following MI, which is critical for maintaining cardiac function and repairing tissues. Targeting of the NLGN3-Gi1/3 signaling pathway may have clinical therapeutic potential in protecting the heart from ischemic injury. What Is Known?O_LIMyocardial infarction (MI) leads to a significantly increased risk of recurrent events in individually vascularized regions, which then stimulates adverse systemic vascular effects. C_LIO_LIGi proteins play a key role in receptor tyrosine kinase (RTK) and other non-GPCR receptor-mediated signaling. C_LIO_LINeuroligin 3 (NLGN3) is a major member of the NLGN family of proteins that help to form synapses between neurons. It is known be cleaved and secreted in an activity-dependent manner, but its function in heart disease is still poorly understood. C_LI What New Information Does This Article Contribute?O_LINLGN3 expression was found to be markedly increased in the heart after MI, especially in cardiac ECs. C_LIO_LIKnockdown of Gi1/3 significantly reduced angiogenesis and impaired cardiac function, while knockdown of NLGN3 increased the ischemic area and reduced angiogenesis through Gi1/3. C_LIO_LINLGN3-Gi1/3 signaling promotes vascular EC proliferation and tube formation through the PI3K-Akt-mTOR pathway, thereby protecting the ischemic heart. C_LI

molecular biology↗

bioRxiv2024

The first near-complete genome assembly of pig: enabling more accurate genetic research

Pigs are crucial sources of meat and protein, valuable animal models, and potential donors for xenotransplantation. However, the existing reference genome for pigs is incomplete, with thousands of segments and missing centromeres and telomeres, which limits our understanding of the important traits in these genomic regions. To address this issue, we present a near complete genome assembly for the Jinhua pig (JH-T2T), constructed using PacBio HiFi and ONT long reads. This assembly includes all 18 autosomes and the X and Y sex chromosomes, with only six gaps. It features annotations of 46.90% repetitive sequences, 35 telomeres, 17 centromeres, and 23,924 high-confident genes. Compared to the Sscrofa11.1, JH-T2T closes nearly all gaps, extends sequences by 177 Mb, predicts more intact telomeres and centromeres, and gains 799 more genes and loses 114 genes. Moreover, it enhances the mapping rate for both Western and Chinese local pigs, outperforming Sscrofa11.1 as a reference genome. Additionally, this comprehensive genome assembly will facilitate large-scale variant detection and enable the exploration of genes associated with pig domestication, such as GPAM, CYP2C18, LY9, ITLN2, and CHIA. Our findings represent a significant advancement in pig genomics, providing a robust resource that enhances genetic research, breeding programs, and biomedical applications.

genomics↗

bioRxiv2024

Deep Video Analysis for Bacteria Genotype Prediction

Genetic modification of microbes is central to many biotechnology fields, such as industrial microbiology, bioproduction, and drug discovery. Understanding how specific genetic modifications influence observable bacterial behaviors is crucial for advancing these fields. In this study, we propose a supervised model to classify bacteria harboring single gene modifications to draw connections between phenotype and genotype. In particular, we demonstrate that the spatiotemporal patterns of Vibrio cholerae growth, recorded in terms of low-resolution bright-field microscopy videos, are highly predictive of the genotype class. Additionally, we introduce a weakly supervised approach to identify key moments in culture growth that significantly contribute to prediction accuracy. By focusing on the temporal expressions of bacterial behavior, our findings offer valuable insights into the underlying mechanisms and developmental stages by which specific genes control observable phenotypes. This research opens new avenues for automating the analysis of phenotypes, with potential applications for drug discovery, disease management, etc. Furthermore, this work highlights the potential of using machine learning techniques to explore the functional roles of specific genes using a low-resolution light microscope.

bioinformatics↗

bioRxiv2024

PSMA-specific CAR-engineered macrophages for therapy of prostate cancer

Chimeric antigen receptor (CAR)-modified macrophages (CAR-Ms) are a promising approach for the treatment of solid tumors due to its high infiltration and immune-regulation activity. Prostate cancer is a typical solid tumor associated with highly immunosuppressive microenvironment. To date, the potential application of CAR-M cell therapy in prostate cancer has been infrequently explored. The prostate-specific membrane antigen (PSMA) functions as a specific biomarker for prostate cancer. In this study, we assessed the antitumor efficacy of PSMA-targeted CAR-Ms in preclinical models. CAR-Ms were engineered to express a PSMA-specific single-chain variable fragment (scFv) and co-stimulatory domains. In vitro data demonstrated specific cytotoxicity of CAR-Ms against PSMA-expressing prostate cancer cells, which was further supported by transcriptome analysis demonstrating the pro-inflammatory phenotypes of CAR-Ms. In vivo studies using xenograft mouse models confirmed significant tumor regression after administration of PSMA-targeted CAR-Ms compared to controls. Histopathological analysis showed infiltration of CAR-Ms into tumor tissues without off-target toxicity. These results highlight the strong antitumor activity and safety of PSMA-targeted CAR-Ms, supporting their potential as a new immunotherapy for prostate cancer.

bioengineering↗

bioRxiv2024

Using TMS-EEG to study the intricate interplay between GABAergic inhibition and glutamatergic excitation during reactive and proactive motor inhibition

Transcranial magnetic stimulation (TMS) studies have provided insight into the neurotransmission underlying motor inhibition but are limited to the primary motor cortex (M1). To investigate {gamma}-aminobutyric acid (GABA) and glutamatergic neurotransmission across the broader motor inhibition network, we combined TMS with electroencephalography (EEG). The N45 and N100 components of the TMS-evoked potentials (TEPs) have been liked to GABAa and GABAb signaling, respectively, whereas the N15, P30 and P60 TEPs are believed to reflect glutamatergic neurotransmission. This study investigates how these components are modulated during reactive and proactive motor inhibition. Twenty-four healthy participants completed two TMS-EEG sessions targeting either the left M1 or the pre-supplementary motor area (preSMA) at rest and during a stop-signal task. We compared TEP amplitudes across TMS conditions (active/sham) and trial types and assessed their relationship with task performance. Participants with a higher N45 amplitude over M1 at rest demonstrated a faster stop-signal reaction time. Active TMS during successful motor inhibition evoked higher N15 amplitudes over preSMA than during uncertain go trials, suggesting that an early excitatory signal from preSMA is crucial for reactive inhibition. In contrast, proactive inhibition was linked to lower P30 amplitudes in M1, possibly reflecting reduced motor facilitation. These findings provide novel empirical insights into the neurophysiological mechanisms underpinning motor inhibition, emphasizing the importance of a coordinated balance between inhibitory processes in M1 and early glutamatergic excitatory signals from preSMA for effective inhibition.

neuroscience↗

bioRxiv2024

Spatiotemporal Single-Cell Roadmap of Human Skin Wound Healing

Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell and spatial transcriptomics analyses on human skin and acute wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization. It shows that pro-inflammatory macrophages and fibroblasts sequentially support keratinocyte migration like a relay race across different healing stages. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds. Additionally, comparing human and mouse acute wound transcriptomes underscores the indispensable value of this roadmap in bridging basic research with clinical innovations. HighlightsO_LIA spatiotemporal atlas to explore human in vivo gene expression across wound healing C_LIO_LIWound margin architecture unveils a model for human re-epithelialization C_LIO_LIDistinct healing challenges in venous ulcers and diabetic foot ulcers C_LIO_LIUnique human healing traits emerge in cellular heterogeneity and gene expression C_LI

cell biology↗

bioRxiv2024

NOK promotes tumorigenesis through coordinating epidermal growth factor receptor to boost the downstream signaling in breast cancer

BACKGROUNDEpidermal growth factor receptor (EGFR) forms a homodimer or heterodimer with other ErbB receptor family members to activate different downstream cytoplasmic signaling proteins during tumorigenesis. METHODSAdenovirus and lentivirus were used to overexpress or deplete NOK and/or EGFR to evaluate the phosphorylation of EGFR, the interaction of NOK-EGFR and their role in cell proliferation and metastasis. RESULTSEGFR heterodimerizes with NOK (also known as STYK1), a novel tyrosine kinase with a transmembrane domain, to promote tumorigenesis and metastasis of breast cancer cells. We found that NOK directly interacted with EGFR and formed a heterodimer complex. Depletion of NOK impaired, but over-expression of NOK increased, the phosphorylation of EGFR. NOK enhanced EGF signaling activation, in particular, the phosphorylation of STAT3, STAT5 and Erk1/2 via its juxtamembrane (JM) domain in promoting the proliferation and migration of breast cancer cells. Overexpression of NOK and EGFR synergistically induced the tumorigenesis of NIH-3T3 normal cells. We finally demonstrated that co-expression of NOK and EGFR correlated with tumor malignant stages in breast cancer patients. CONCLUSIONSOur findings uncover a mechanism by which NOK coordinates EGFR to enhance EGF signaling during tumorigenesis and metastasis and propose a potential strategy for targeting NOK-EGFR in breast cancer treatment. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/608018v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@17b0078org.highwire.dtl.DTLVardef@5bfe6forg.highwire.dtl.DTLVardef@19d3d15org.highwire.dtl.DTLVardef@155fc4_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIEGFR heterodimerizes with NOK/STYK1, a novel tyrosine kinase with a transmembrane domain, in a manner of cross interaction via their juxtamembrane (JM) domains and kinase domains. C_LIO_LINOK enhances EGF signaling activation, in particular, the phosphorylation of STAT3, STAT5 and Erk1/2 via its JM domain. C_LIO_LINOK and EGFR synergistically promote proliferation and migration of breast cancer cells and induce tumorigenesis of normal cells. C_LIO_LICo-expression of NOK and EGFR correlates with tumor malignant stages in breast cancer patients. C_LI

cell biology↗

bioRxiv2024

Ubiquitination mediates protein localization in RNA virus-infected cells

Viruses trigger monocytes proinflammatory and antiviral responses. Ubiquitination, a post-translational modification primarily marking proteins for degradation, regulates cellular responses to virus infection. However, a comprehensive analysis of virus-induced ubiquitination in monocytes is lacking. Here we identified a widespread increase of ubiquitination under viral RNA challenge or influenza infection in monocytes. Systematic proteome studies revealed that influenza infection elicits dynamic ubiquitinome alterations, with a notable transition from early to late stage. Most of this increased ubiquitination is not proteolytic and targets proteins involved in subcellular localization, such as the mitochondrial protein COA7 which, when ubiquitinated during infection, translocates to the nucleus and inhibits stress granules formation and TNF- expression. Blocking ubiquitination halts viral ribonucleoproteins nuclear export, highlighting ubiquitinations importance for protein localization during virus infection.

molecular biology↗

bioRxiv2024

Aerolysin nanopore structure revealed at high resolution in lipid environment

Aerolysin is a {beta}-pore-forming toxin produced by most Aeromonas bacteria which has attracted large attention in the field of nanopore sensing due to its narrow and charged pore lumen. Structurally similar proteins, belonging to the aerolysin-like family, are present throughout all kingdoms of life, but very few of them have been structurally characterized in a lipid environment. Here we present the first high-resolution atomic cryo-EM structures of aerolysin pre-pore and pore in a membrane-like environment. These structures allow the identification of key interactions, which are relevant for the pore formation and for positioning the pore barrel into the membrane with the anchoring {beta}-turn motif now finally observed. Moreover, we elucidate at high resolution the architecture of key mutations and precisely identify four constriction rings in the pore lumen that are highly relevant for nanopore sensing experiments.

biochemistry↗

bioRxiv2024

PGSFusion streamlines polygenic score construction and epidemiological applications in biobank-scale cohorts

BackgroundThe polygenic score (PGS) is an estimate of an individuals genetic susceptibility to a specific complex trait and has been instrumental to the development of precision medicine. Clinically, the simplest form of PGS, which is calculated as a weighted sum of variant counts, has been widely applied to conduct disease risk classification. Unfortunately, despite the critical importance of PGS, there are few online resources available to biologists and epidemiologists to calculate PGS in a user-friendly manner. ResultsTo address this need, we have developed a web server, PGSFusion, that streamlines the construction of PGS using a large variety of methods targeting different epidemiological requirements. PGSFusion included 16 PGS methods in four categories, which are single-trait, annotation-based, multiple-trait, and cross-ancestry. In addition, PGSFusion also utilizes UK Biobank data to provide two kinds of in-depth analyses: i) prediction performance evaluation to display the consistency between PGS and specific traits and the effect size of PGS in different genetic risk groups; ii) joint effect analysis to investigate the interaction between PGS and covariates, as well as the genetic effect size in different subgroups of covariates. PGSFusion automatically identifies the required information in uploaded summary statistics files, provides a selection of suitable methods, and outputs calculated PGSs and their corresponding epidemiological results, all without requiring prior programming knowledge. To demonstrate the function of PGSFusion, we showcase three case studies in different application scenario, highlighting its versatility and values to researchers. ConclusionsOverall, PGSFusion presents an easy-to-use, effective, and extensible platform for PGS construction, promoting the accessibility and utility of PGS for researchers in the field of precision medicine.

bioinformatics↗