{
  "abstract": "Inhibitor potency is commonly assessed from population-average responses, but how much single-cell signaling remains under strong average suppression is less clear. We measured nuclear STAT1 and STAT3 tyrosine phosphorylation in two human monocytic cell lines stimulated with IFN-{gamma}; and IL-10 and treated with six JAK-pathway inhibitors. Across 24 profiles, we compared arithmetic-mean inhibition and inhibition of the mean of log10-transformed single-cell responses (log-mean) with the fractions of cells leaving the stimulated range (partial inhibition) or entering the non-stimulated range (complete inhibition). At the lowest tested doses where arithmetic-mean or log-mean inhibition reached at least 80%, median fractions remaining above the non-stimulated range were 76% and 37%, respectively. Thus, strong average suppression frequently left substantial fractions of cells with tangibly elevated pY-STAT responses. Log-mean inhibition generally approximated partial-inhibition occupancy, whereas the apparent IC50 for complete-inhibition occupancy was a median 2.4-fold higher than the log-mean IC50 and 7.4-fold higher than the arithmetic-mean IC50. These relationships provide an empirical guide for estimating cell fractions from conventional inhibition curves.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "K. E. Zakrzewska"
    },
    {
      "name": "J. Walczak"
    },
    {
      "name": "K. Nienałtowski"
    },
    {
      "name": "P. Topolewski"
    },
    {
      "name": "C. M. Wagner"
    },
    {
      "name": "A. Braniewska"
    },
    {
      "name": "T. Rygiel"
    },
    {
      "name": "R. Moriggl"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Komorowski"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dpvva9ra48ewx.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.26.759076",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.759076v1.full",
  "id": "dpvva9ra48ewx",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.759076v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "systems biology"
    ],
    [
      "openalex",
      "2730|Cytokine Signaling Pathways and Interactions"
    ]
  ],
  "openalex": "W7224110266",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.759076v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dpvva9ra48ewx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:02Z",
      "native_id": "10.64898/2026.10.26.759076",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.26.759076v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:systems biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Single-cell profiling quantifies the dose gap between population-average and complete pY-STAT1/3 suppression by JAK inhibitors",
  "title_text": "Single-cell profiling quantifies the dose gap between population-average and complete pY-STAT1/3 suppression by JAK inhibitors",
  "type": "preprint",
  "updated_at": "2026-10-30T12:30:02Z",
  "url": "https://research.draconitic.com/paper/dpvva9ra48ewx",
  "venue": "bioRxiv",
  "versions": []
}