{
  "abstract": "Activating and inhibitory interactions jointly shape cellular regulation, yet it remains unclear whether their allocation among individual targets exhibits systematic organization beyond basic structural constraints. Here we introduce antagonistic--cooperative polarization, a target-wise principle in which the sign of each regulatory interaction is determined by the class of its target. This formulation yields a node-separable graph polarization index and decomposes departures from perfect polarization exactly into localized conflicts at targets receiving both activating and inhibitory inputs. We applied the framework to 98 pathway-associated regulatory subnetworks reconstructed from a unified signed regulatory network. Target-wise sign consistency was generally high, but the key evidence for non-random organization came from constrained null models: mixed-input targets were depleted relative to both global sign shuffling and degree-preserving directed rewiring, with depletion increasing systematically with pathway size. This association was robust to rewiring-mobility and pathway-overlap analyses, and indegree-stratified analysis identified the clearest statistically supported depletion among targets receiving exactly two signed inputs. Mixed-input organization was pathway-specific but recurrent across genes; recurrent mixed-input targets remained enriched for Cancer Gene Census genes after accounting for pathway opportunity. Mixed-input occurrences were also preferentially associated with signed feedback motifs, particularly negative feedback, whereas downstream reach was not increased. Together, these results reveal a prevalent polarized backbone punctuated by localized sites of opposing regulation whose abundance departs from expectations under complementary null models controlling for network topology, sign composition, degree structure, and source-specific regulatory output.",
  "abstract_shown": true,
  "affiliations": [
    "University of Magna Graecia"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "A. Procopio"
    },
    {
      "name": "R. Granata"
    },
    {
      "name": "P. Zaffino"
    },
    {
      "name": "A. Merola"
    },
    {
      "name": "F. Amato"
    },
    {
      "affs": [
        0
      ],
      "name": "C. Cosentino"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9x6r4q967aqt8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.09.758118",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.758118v1.full",
  "id": "9x6r4q967aqt8",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.758118v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "systems biology"
    ],
    [
      "openalex",
      "1312|Gene Regulatory Network Analysis"
    ]
  ],
  "openalex": "W7222828836",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.758118v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9x6r4q967aqt8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:16Z",
      "native_id": "10.64898/2026.10.09.758118",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.09.758118v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:systems biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Polarization of regulatory inputs reveals structural constraints in reconstructed pathway-associated regulatory networks",
  "title_text": "Polarization of regulatory inputs reveals structural constraints in reconstructed pathway-associated regulatory networks",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:16Z",
  "url": "https://research.draconitic.com/paper/9x6r4q967aqt8",
  "venue": "bioRxiv",
  "versions": []
}