{
  "abstract": "A constraint-first framework for future ‘prompt-to-genome’ AI across Bacteria, Archaea, Eukaryota, and viruses is proposed. Genome-scale models can now generate long DNA sequences, and experimentally viable genome-scale designs have begun to appear, but sequence generation alone does not establish biological feasibility. Constraints should not require designs to remain within natural sequence space; rather, they should define testable boundaries for function, inheritance, lifecycle coherence and safe use, including new-to-nature designs. We propose a two-part system. First, a Constraint Compiler translates natural-language prompts into machine-checkable specifications defining scope, context, objectives, assumptions and governance requirements. Second, a modular Validator Stack (C1–C6) evaluates candidate designs for sequence integrity, gene and regulatory plausibility, genome completeness, comparative coherence, systems-level feasibility, and safety and governance. Extreme prompts serve as stress tests to expose hidden assumptions, conflicting objectives, and refusal points, complemented by adversarial testing and risk assessment. A phased roadmap and community benchmarks are proposed to measure specification accuracy, biological feasibility, robustness, and governance performance. The goal is to move prompt-to-genome systems from impressive generation toward reliable, auditable, and accountable biological design.",
  "abstract_shown": true,
  "affiliations": [
    "Aether Biomics, Tanah Abang, Jakarta, Indonesia",
    "Department of Biotechnology, School of Health and Life Sciences, i3L University, Pulo Gadung, Jakarta, Indonesia"
  ],
  "article_type": "Perspective",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Adhityo Wicaksono"
    },
    {
      "affs": [
        1
      ],
      "name": "Arli Aditya Parikesit"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cz0654kzr16b2.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pcbi.1014865",
  "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014865",
  "id": "cz0654kzr16b2",
  "issns": [
    "1553-7358"
  ],
  "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014865",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Genomics and Phylogenetic Studies"
    ],
    [
      "plos",
      "/Biology and life sciences/Bioengineering/Biotechnology/Plant biotechnology/Plant genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Computational biology/Genome analysis/Genome annotation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Animal genomics/Mammalian genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genome analysis/Genome annotation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Microbial genomics/Viral genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Plant genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Plant genetics/Plant genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Microbial genomics/Viral genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cognitive science/Cognitive psychology/Language"
    ],
    [
      "plos",
      "/Biology and life sciences/Plant science/Plant biotechnology/Plant genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Plant science/Plant genetics/Plant genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Psychology/Cognitive psychology/Language"
    ],
    [
      "plos",
      "/Engineering and technology/Bioengineering/Biotechnology/Plant biotechnology/Plant genomics"
    ],
    [
      "plos",
      "/Medicine and health sciences/Epidemiology/Medical risk factors"
    ],
    [
      "plos",
      "/Research and analysis methods/Research design/Experimental design"
    ],
    [
      "plos",
      "/Social sciences/Psychology/Cognitive psychology/Language"
    ]
  ],
  "openalex": "W7222131080",
  "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014865&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-15",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/cz0654kzr16b2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:23Z",
      "native_id": "10.1371/journal.pcbi.1014865",
      "source": "plos",
      "url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014865"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "From prompts to genomes: A constraint-first framework for AI-driven sequence design across life and viruses",
  "title_text": "From prompts to genomes: A constraint-first framework for AI-driven sequence design across life and viruses",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:23Z",
  "url": "https://research.draconitic.com/paper/cz0654kzr16b2",
  "venue": "PLOS Computational Biology",
  "versions": []
}