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arXiv cs.CL· Doniyorkhon Obidov, Xiaolong Guo, Yonghui Li, Kaichen Yang·· 15 小时前AI 评分38

Genotypic Triggers:生成式抗菌肽模型中的宿主特异性后门与药物基因组盲区

Genotypic Triggers: Exposing Pharmacogenomic Blind Spots via Host-Specific Backdoors in Generative Antimicrobial Peptide Models

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研究者提出 Genotypic Trigger 后门攻击,可操纵抗菌肽生成模型,使携带特定 HLA 等位基因者的预测免疫原性风险平均升高 743%,非携带者则接近自然基线。被植入后门的模型仍保持高抗菌活性与低一般毒性,能通过常规安全筛查。

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Abstract:Large Language Models (LLMs) have accelerated drug discovery, particularly in the automated design of antimicrobial peptides (AMPs). However, current validation pipelines for peptide generation models overlook historical precedents showing that certain drugs carry health risks predominantly for individuals with specific genetic profiles. In this paper, we demonstrate that such targeted health risks can be induced intentionally and at scale by manipulating models that generate peptide candidates. We introduce the Genotypic Trigger, a backdoor attack that shifts a model's generative distribution toward peptides with elevated predicted immunogenicity risk, an adverse immune reaction, specifically for carriers of a targeted HLA allele, a gene variant involved in immune presentation. Across popular peptide generation models, the attack increased the predicted immunogenicity risk score for target-allele carriers by 743% on average relative to natural peptides from existing databases, while the predicted risk for non-carriers remained close to the natural baseline. Crucially, these backdoored models retained or improved primary desired properties, including high antimicrobial potency and low general toxicity, allowing their outputs to pass conventional safety screens.
Subjects: Quantitative Methods (q-bio.QM); Artificial Intelligence (cs.AI); Computation and Language (cs.CL)
Cite as: arXiv:2608.06779 [q-bio.QM]
  (or arXiv:2608.06779v2 [q-bio.QM] for this version)
  https://doi.org/10.48550/arXiv.2608.06779

arXiv-issued DOI via DataCite

Submission history

From: Doniyorkhon Obidov [view email]
[v1] Fri, 7 Aug 2026 03:54:54 UTC (4,246 KB)
[v2] Mon, 26 Oct 2026 16:43:55 UTC (3,647 KB)

来源:arXiv cs.CL · arxiv.org