Biology subjects

Zai, X.

Publications and source records attributed to Zai, X..

3 recordsLinked to original sources

bioRxiv2026

SemVac: A Semantic Vaccinology Paradigm Powered by LLMs for Antigen Discovery

Reverse vaccinology identifies vaccine antigens from pathogen genomes, yet existing methods rely mainly on sequence and structure and overlook the functional and immunological knowledge recorded in the published literature. We introduce semantic vaccinology, a paradigm in which large language models (LLMs) reason over literature-derived protein descriptions to predict protective antigens. Implemented as SemVac, the workflow retrieves publications linked to each protein through PaperBLAST, condenses the evidence into a structured semantic profile, and prompts an LLM to return an antigenicity probability. Benchmarked against a curated 246-protein bacterial benchmark and the specialized protein-language and geometric-deep-learning predictor PLGDL, the best of 14 general-purpose LLMs matched or exceeded the precision of PLGDL; the open-weight Kimi K2 0905 offered the strongest performance-cost balance. Predictions were robust to masking of vaccine keywords, reproducible across repeated inference, and generalized to a 1,200-protein cross-pathogen dataset. Surprisingly, explicit chain-of-thought reasoning increased recall but lowered precision in every model tested, revealing over-reasoning in biological scoring. Applied to the mpox virus proteome, SemVac recovered the established mpox antigen repertoire and prioritized uncharacterized candidates. Two of these, A30L and C19L, received independent experimental support in recent orthopoxvirus vaccine development, providing external validation. For one candidate, B20R, the model generated a coherent but false TNF-decoy narrative unsupported by curated annotations, demonstrating that LLM confabulation can be detected when reasoning traces are cross-checked against curated resources. Semantic vaccinology therefore establishes the literature as an explicit, auditable third modality alongside sequence and structure, while making its failure modes transparent and correctable.

immunology↗

bioRxiv2026

Conversion of a Viral Glycan Shield into a Binding Anchor via Causal-Driven Antibody Optimization

Therapeutic antibodies are challenged by rapidly evolving pathogens that exploit glycosylation to shield epitopes. SARS-CoV-2 JN.1 exemplifies this, escaping antibodies through the N354-linked glycan. However, targeting glycosylated epitopes remains vacant, as scarce and heterogeneous glycan structures render existing approaches ineffective. Here, we introduce the Antibody Evolution Nexus with Causal-Driven Simulation (AENCS), integrating molecular simulation with causal inference. Applying AENCS to restore S309 efficacy against JN.1, we identified ACC01, exhibiting [~]24-fold improved neutralization. With limited prior knowledge of the N354 glycosylation site, ACC01 stabilized this glycan conformation, facilitating the determination of its cryo-EM structure. Causal dissection revealed how this glycan shield is functionally inverted into a binding anchor through multi-layered interactions. This mechanistic conversion, combined with the conservation of N354 glycosylation, enabled ACC01 to maintain potent activity against the latest variant NB.1.8.1. Collectively, AENCS demonstrates causal-driven antibody engineering can illuminate cryptic glycosylated epitopes, providing viable paradigms for exploring this vacant frontier.

bioengineering↗

bioRxiv2024

The penetration ring is a novel infection structure formed by the penetration peg for invading plant cell membrane in rice blast fungus

Many fungal pathogens develop specialized infection structures such as appressoria to penetrate plant cells. However, it is not clear whether special structures are formed after cell wall penetration before invading host plasma membrane in hemibiotrophic pathogens. Here, we showed that a penetration ring consisting of Ppe1 secreted proteins is formed after appressorium-mediated cell wall penetration and remained at the base of penetration site after invading plant plasma membrane by the rice blast fungus Magnaporthe oryzae. The same persistent Ppe1 ring is formed after the penetration of neighboring cells by transpressoria. PPE1 is specifically expressed during plant infection and the {Delta}ppe1 mutant is defective in penetration and invasive growth. Blockage of penetration peg formation impedes the development of the Ppe1 ring. Close examinations showed that the penetration ring is formed at the collar of penetration pegs between the plant cell wall and plasma membrane and it is persistent as a fixed ring even after invasive hyphae invaded neighboring cells. Furthermore, Ppe1 is a member of an expanded family of secreted proteins that are unique to fungal pathogens using extreme appressorium turgor for plant penetration. Other members of the Ppe1 family also localize to the penetration ring for anchoring on plasma membrane during plant infection. Taken together, a penetration ring consisting of a family of secreted proteins is formed between plant cell wall and plasma membrane, which may function as a novel physical structure at the interface between the tip of penetration pegs and plant plasma membrane before the differentiation of invasive hyphae. Significance StatementLike many other plant pathogens, the rice blast fungus forms melanized appressoria (specialized infection structures) to penetrate plant cells. In this study, we showed that a penetration ring is formed by penetration pegs after appressorium-mediated penetration of plant cell wall. This ring of secreted proteins is persistent at the point of penetration pegs invading plant plasma membrane to form invasive hyphae. Therefore, after the penetration of plant cell wall, the rice blast fungus forms a penetration ring that consists of a family of secreted proteins unique to pathogens using extreme appressorium turgor for penetration and may function as a physical structure for anchoring onto plant plasma membrane and developing invasive hyphae in penetrated cells.

pathology↗