{
  "abstract": "Boolean networks are powerful frameworks for capturing the logic of gene-regulatory circuits, yet their combinatorial explosion hampers exhaustive analyses. Here, we present a systematic reduction of a published 31-node Boolean model that describes cisplatin- and pemetrexed-resistance in non-small-cell lung cancer to a compact 9-node core that exactly reproduces the original attractor landscape. Through a sequence of biologically guided reductions (31→29→14→9 nodes), the streamlined network shrinks the state space by four orders of magnitude, enabling rapid exploration of critical control points, rules fitting, and candidate therapeutic targets. Extensive synchronous and asynchronous simulations, combined with a Boolean rule-fitting algorithm that removes spurious limit cycles, confirm that the three clinically relevant steady states and their basins of attraction are conserved and reflect resistance frequencies close to those reported in clinical studies. The reduced model provides an accessible scaffold for future mechanistic and drug-discovery studies.",
  "abstract_shown": true,
  "affiliations": [
    "Facultad de Ingenieria y Ciencias, Univesidad Adolfo Ibañez, Santiago, Chile",
    "Laboratoire d’Informatique et Systèmes, Centre National de la Recherche Scientifique, Aix-Marseille Univesité, Marseille, France",
    "Millennium Nucleus for Social Data Science (SODAS), Santiago, Chile"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Alonso Espinoza"
    },
    {
      "affs": [
        1
      ],
      "name": "Eric Goles"
    },
    {
      "affs": [
        2
      ],
      "name": "Marco Montalva-Medel"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9ahfezcpz2q49.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0357764",
  "fulltext_url": null,
  "id": "9ahfezcpz2q49",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0357764",
  "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|Gene Regulatory Network Analysis"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/DNA/DNA damage"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Post-translational modification/Phosphorylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell death/Apoptosis"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/DNA/DNA damage"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene identification and analysis/Genetic networks"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene types/Suppressor genes/Tumor suppressor genes"
    ],
    [
      "plos",
      "/Computer and information sciences/Data management/Data visualization/Infographics/Graphs"
    ],
    [
      "plos",
      "/Computer and information sciences/Information theory/Graph theory/Directed graphs"
    ],
    [
      "plos",
      "/Computer and information sciences/Network analysis/Genetic networks"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Lung and intrathoracic tumors/Non-small cell lung cancer"
    ],
    [
      "plos",
      "/Physical sciences/Mathematics/Graph theory/Directed graphs"
    ]
  ],
  "openalex": "W4415133729",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0357764&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-15",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/9ahfezcpz2q49.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:50Z",
      "native_id": "10.1371/journal.pone.0357764",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0357764"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:genetics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Boolean-network simplification and rule fitting to unravel chemotherapy resistance in non-small cell lung cancer",
  "title_text": "Boolean-network simplification and rule fitting to unravel chemotherapy resistance in non-small cell lung cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:50Z",
  "url": "https://research.draconitic.com/paper/9ahfezcpz2q49",
  "venue": "PLOS One",
  "versions": []
}