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SVNeoPP: A Workflow for Structural-Variant-Derived Neoantigen Prediction and Prioritization Using Multi-Omics Data

Biology (Basel). 2026 Mar 19;15(6):492. doi: 10.3390/biology15060492.

ABSTRACT

BACKGROUND: Tumor neoantigens are key targets for personalized vaccines and T-cell therapies, yet most pipelines focus on neoantigens derived from SNV/small indel and often yield a limited number of high-quality candidates. SVs are prevalent in tumors and can generate novel chimeric sequences and neopeptides, making them a promising additional source of neoantigens. However, SV-derived neoantigen prediction remains challenging due to breakpoint uncertainty, isoform-dependent coding inference, and limited integration of multi-dimensional evidence and reproducibility.

METHODS: We developed SVNeoPP (Structural Variant Neoantigen Prediction and Prioritization), an end-to-end workflow for SV-derived neoantigen analysis. SVNeoPP takes WGS and RNA-seq as inputs, performs SV calling and annotation, and reconstructs altered transcripts and coding sequences in a traceable, isoform-aware manner to generate candidate peptides. Candidates are prescreened by integrating antigen-processing features with HLA binding prediction, and then hierarchically filtered and prioritized based on transcript expression, LC-MS/MS proteomics evidence, immunogenicity predictions, and sequence similarity to experimentally validated neoantigen databases. SVNeoPP is implemented in Snakemake to enable modular extension, checkpoint-based restarts, and end-to-end reproducibility.

RESULTS: Using a hepatocellular carcinoma (HCC) multi-omics dataset as a proof of concept, we demonstrated the performance of SVNeoPP and obtained a high-priority shortlist of candidate peptides. Compared with other methods, SVNeoPP substantially expanded the candidate search space for SV-derived neoantigens and showed more favorable distributions of antigen-processing and HLA binding features.

CONCLUSIONS: SVNeoPP provides a reusable, traceable, and interpretable multi-dimensional evidence-driven framework for SV-derived neoantigens. As a complementary module to SNV/small-indel pipelines, it broadens the neoantigen candidate repertoire and generates ranked candidates with interpretable evidence to facilitate downstream prioritization and decision-making.

PMID:41892252 | PMC:PMC13024079 | DOI:10.3390/biology15060492

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Accelerating Robotic Reinforcement Learning with Agent Guidance

arXiv:2602.11978v2 Announce Type: replace-cross Abstract: Reinforcement Learning (RL) offers a powerful paradigm for autonomous robots to master generalist manipulation skills through trial-and-error. However, its real-world application is stifled by low sample efficiency. Recent Human-in-the-Loop (HIL) methods accelerate training by using human corrections, yet this approach faces a scalability barrier. Reliance on human supervisors imposes a 1:1 supervision ratio that limits scalability, suffers from operator fatigue over extended sessions, and introduces high variance due to inconsistent human proficiency. We present Agent-guided Policy Search (AGPS), a framework that automates the training pipeline by replacing human supervisors with a multimodal agent. Our key insight is that the agent can be viewed as a semantic world model, injecting intrinsic value priors to structure physical exploration. By using tools, the agent provides precise guidance via corrective waypoints and spatial constraints for exploration pruning. We validate our approach on three tasks, ranging from precision insertion to deformable object manipulation. Results demonstrate that AGPS outperforms HIL methods in sample efficiency. This automates the supervision pipeline, unlocking the path to labor-free and scalable robot learning. Project website: https://agps-rl.github.io/agps/.
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