Biology subjects

xu, y.

Publications and source records attributed to xu, y..

5 recordsLinked to original sources

bioRxiv2025

Quantifying Protein-Protein Interaction with a Spatial Attention Kinetic Graph Neural Network

Accurate prioritisation of near-native protein-protein interaction (PPI) models remains a major bot-tleneck in structural biology. Here we present SAKE-PP, a physics-inspired, spatial-attention equivariant graph neural network that directly regresses interface RMSD (iRMSD) without any native references. Trained on docking decoys generated through our novel hierarchical sampling strategy applied to PDB-Bind dataset, SAKE-PP combines force-field-like attention with Laplacian-eigenvector orientation to couple local interaction forces with global topology. On the 2024PDB benchmark comprising 176 het-erodimers, SAKE-PP demonstrates effective optimization and selection of AF3 decoys, achieving improvements of 13.75% based on iRMSD statistics and 12.5% based on DockQ scores. It consistently outperforms the AF3 ranking score in multiple metrics, including overlap, hit rate, and correlation. In zero-shot evaluation of 139 antibody-antigen complexes, SAKE-PP improves the score-iRMSD correlation by 0.4. By unifying geometric deep learning with physics-based realism, SAKE-PP provides a robust, plug-and-play scoring function that streamlines reliable PPI evaluation and accelerates downstream structure-guided drug-design workflows.

bioinformatics↗

bioRxiv2025

Bayesian model-averaging of parametric coalescent models for phylodynamic inference

Bayesian phylodynamic models have become essential for reconstructing population history from genetic data, yet their accuracy depends crucially on choosing appropriate demographic models. To address uncertainty in model choice, we introduce a Bayesian Model Averaging (BMA) framework that integrates multiple parametric coalescent models- including constant, exponential, logistic, and Gompertz growth-along with their "expansion" variants that account for non-zero ancestral populations. Implemented in a Bayesian setting with Metropolis-coupled MCMC, this approach allows the sampler to switch among candidate growth functions, thereby capturing demographic histories without having to pre-specify a single model. Simulation studies verify that the logistic and Gompertz models may require specialised sampling strategies such as adaptive multivariate proposals to achieve robust mixing. We demonstrate the performance of these models on datasets simulated under different substitution models, and show that joint inference of genealogy and population parameters is well-calibrated when properly incorporating correlated-move operators and BMA. We then apply this method to two real-world datasets. Analysis of Egyptian Hepatitis C virus (HCV) sequences indicates that models with a founder population followed by a rapid expansion are well supported, with a slight preference for Gompertz-like expansions. Our analysis of a single metastatic colorectal cancer (CRC) single-cell dataset suggests that exponentiallike growth is plausible even for an advanced stage cancer patient. We believe this highlights that tumour subclones may retain substantial proliferative capacity into the later stages of the disease. Overall, our unified BMA framework reduces the need for restrictive model selection procedures and can also provide deeper biological insights into epidemic spread and tumour evolution. By systematically integrating multiple growth hypotheses within a standard Bayesian setting, this approach naturally avoids overfitting and offers a powerful tool for inferring population histories across diverse biological domains.

evolutionary biology↗

bioRxiv2020

The COMPASS-like complex modulates fungal development and pathogenesis by regulating H3K4me3-mediated targeted gene expression in Magnaporthe oryzae

Histone H3K4 methylation is catalysed by the multi-protein complex known as the Set1/COMPASS or MLL/COMPASS-like complex, an element that is highly evolutionarily conserved from yeast to humans. However, the components and mechanisms by which the COMPASS-like complex targets the H3K4 methylation of plant pathogenic genes in fungi remain elusive. Here we present a comprehensive analysis combining biochemical, molecular, and genome-wide approaches to characterize the roles of the COMPASS-like family in Magnaporthe oryzae, a model plant fungal pathogen. We purified and identified six conserved subunits of COMPASS from the rice blast fungus M. oryzae, i.e., MoBre2 (Cps60/ASH2L), MoSpp1 (Cps40/Cfp1), MoSwd2 (Cps35), MoSdc1 (Cps25/DPY30), MoSet1 (MLL/ALL) and MoRbBP5 (Cps50), using an affinity tag on MoBre2. We determined the SPRY domain of MoBre2 can recognize directly with DPY30 domain of MoSdc1 in vitro. Furthermore, we found that deletion of the genes encoding COMPASS subunits of MoBre2, MoSpp1 and MoSwd2 caused similar defects regarding invasive hyphal development and pathogenicity. Genome-wide profiling of H3K4me3 revealed that the it has remarkable co-occupancy at the TSS regions of target genes. Significantly, these target genes are often involved in spore germination and pathogenesis. Decreased gene expression caused by the deletion of MoBre2, MoSwd2 or MoSpp1 gene was highly correlated with decrease in H3K4me3. Taken together, these results suggest that MoBre2, MoSpp1, and MoSwd2 function as a whole COMPASS complex, contributing to fungal development and pathogenesis by regulating H3K4me3-targeted genes in M. oryzae.

microbiology↗

bioRxiv2019

INeo-Epp: T-cell HLA class I immunogenic or neoantigenic epitope prediction via random forest algorithm based on sequence related amino acid features

In silico T-cell epitope prediction plays an important role in immunization experimental design and vaccine preparation. Currently, most epitope prediction research focuses on peptide processing and presentation, e.g. proteasomal cleavage, transporter associated with antigen processing (TAP) and major histocompatibility complex (MHC) combination. To date, however, the mechanism for immunogenicity of epitopes remains unclear. It is generally agreed upon that T-cell immunogenicity may be influenced by the foreignness, accessibility, molecular weight, molecular structure, molecular conformation, chemical properties and physical properties of target peptides to different degrees. In this work, we tried to combine these factors. Firstly, we collected significant experimental HLA-I T-cell immunogenic peptide data, as well as the potential immunogenic amino acid properties. Several characteristics were extracted, including amino acid physicochemical property of epitope sequence, peptide entropy, eluted ligand likelihood percentile rank (EL rank(%)) score and frequency score for immunogenic peptide. Subsequently, a random forest classifier for T cell immunogenic HLA-I presenting antigen epitopes and neoantigens was constructed. The classification results for the antigen epitopes outperformed the previous research (the optimal AUC=0.81, external validation data set AUC=0.77). As mutational epitopes generated by the coding region contain only the alterations of one or two amino acids, we assume that these characteristics might also be applied to the classification of the endogenic mutational neoepitopes also called neoantigens. Based on mutation information and sequence related amino acid characteristics, a prediction model of neoantigen was established as well (the optimal AUC=0.78). Further, an easy-to-use web-based tool INeo-Epp was developed (available at http://www.biostatistics.online/INeo-Epp/neoantigen.php)for the prediction of human immunogenic antigen epitopes and neoantigen epitopes.

immunology↗

bioRxiv2019

Toxic Effects of Crude Extracts from Chinese Herbal Toothpastes on Solenopsis invicta (Hymenoptera: Formicidae)

Red imported fire ant is an invasive species with the characteristics of quick dispersion, strong ferocity and aggression. For a long time, chemical control has been used as a main means of prevention and control of this pest, but the long-term use of high toxic pesticides will lead to a serious impact on the environment and non-target organisms. The toxicity of Chinese herbal toothpaste and its crude extracts against red imported fire ant was evaluated in the laboratory bioassay. The results showed that the traditional Chinese medicine toothpaste with watermelon cream has significant toxicity to red imported fire ants. The mortality reached more than 80% after 48h treatment, and the mortality was 100% after 72h treatment. Among the fractions separated from watermelon cream after the extraction of toothpaste, the ethyl acetate fraction has higher activity, and the mortality was more than 80% when the concentration was 1% after 72h. Our results suggest that Chinese herbal toothpaste is toxic to insects and have the potential for bait application in pest control.

animal behavior and cognition↗