{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:15:30Z","timestamp":1789496130969,"version":"build-2803163510"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    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 (\n                    <jats:inline-formula id=\"pone.0357764.e001\">\n                      <jats:alternatives>\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" id=\"pone.0357764.e001g\" mimetype=\"image\" position=\"anchor\" xlink:href=\"info:doi\/10.1371\/journal.pone.0357764.e001\" xlink:type=\"simple\"\/>\n                        <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" display=\"inline\" id=\"M1\">\n                          <mml:mrow>\n                            <mml:mn>31<\/mml:mn>\n                            <mml:mo>\u2192<\/mml:mo>\n                            <mml:mn>29<\/mml:mn>\n                            <mml:mo>\u2192<\/mml:mo>\n                            <mml:mn>14<\/mml:mn>\n                            <mml:mo>\u2192<\/mml:mo>\n                            <mml:mn>9<\/mml:mn>\n                          <\/mml:mrow>\n                        <\/mml:math>\n                      <\/jats:alternatives>\n                    <\/jats:inline-formula>\n                    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.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0357764","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T17:55:15Z","timestamp":1789494915000},"page":"e0357764","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Boolean-network simplification and rule fitting to unravel chemotherapy resistance in non-small cell lung cancer"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4643-5003","authenticated-orcid":true,"given":"Alonso","family":"Espinoza","sequence":"first","affiliation":[{"name":"Univesidad Adolfo Iba\u00f1ez","place":["Santiago, Chile"],"department":["Facultad de Ingenieria y Ciencias"]},{"name":"Aix-Marseille Univesit\u00e9","place":["Marseille, France"],"department":["Laboratoire d\u2019Informatique et Syst\u00e8mes, Centre National de la Recherche Scientifique"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Goles","sequence":"additional","affiliation":[{"name":"Univesidad Adolfo Iba\u00f1ez","place":["Santiago, Chile"],"department":["Facultad de Ingenieria y Ciencias"]},{"name":"Millennium Nucleus for Social Data Science (SODAS)","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7264-9840","authenticated-orcid":true,"given":"Marco","family":"Montalva-Medel","sequence":"additional","affiliation":[{"name":"Univesidad Adolfo Iba\u00f1ez","place":["Santiago, Chile"],"department":["Facultad de Ingenieria y Ciencias"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"pone.0357764.ref001","doi-asserted-by":"crossref","first-page":"15009","DOI":"10.1038\/nrdp.2015.9","article-title":"Non-small-cell lung cancer","volume":"1","author":"C Gridelli","year":"2015","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"pone.0357764.ref002","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ncrna.2023.10.008","article-title":"A dynamic Boolean network reveals that the BMI1 and MALAT1 axis is associated with drug resistance by limiting miR-145-5p in non-small cell lung cancer","volume":"9","author":"S Gupta","year":"2023","journal-title":"Noncoding RNA Res"},{"key":"pone.0357764.ref003","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1023\/A:1023905711304","article-title":"On Learning Gene Regulatory Networks Under the Boolean Network Model","volume":"52","author":"H L\u00e4hdesm\u00e4ki","year":"2003","journal-title":"Machine Learning"},{"issue":"6","key":"pone.0357764.ref004","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.dam.2010.10.010","article-title":"Combinatorics on update digraphs in Boolean networks","volume":"159","author":"J Aracena","year":"2011","journal-title":"Discrete Applied Mathematics"},{"issue":"6","key":"pone.0357764.ref005","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1007\/s11538-012-9794-1","article-title":"Deconstruction and dynamical robustness of regulatory networks: application to the yeast cell cycle networks","volume":"75","author":"E Goles","year":"2013","journal-title":"Bull Math Biol"},{"issue":"2","key":"pone.0357764.ref006","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.mbs.2013.01.007","article-title":"On the number of different dynamics in Boolean networks with deterministic update schedules","volume":"242","author":"J Aracena","year":"2013","journal-title":"Math Biosci"},{"key":"pone.0357764.ref007","volume-title":"R: A language and environment for statistical computing","author":"RCore Team","year":"2021"},{"issue":"10","key":"pone.0357764.ref008","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1093\/bioinformatics\/btq124","article-title":"BoolNet--an R package for generation, reconstruction and analysis of Boolean networks","volume":"26","author":"C M\u00fcssel","year":"2010","journal-title":"Bioinformatics"},{"key":"pone.0357764.ref009","unstructured":"Python Software Foundation. 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