{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:20Z","timestamp":1792790360379,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,18]]},"group-title":"Systems Biology","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["R35GM128717"],"award-info":[{"award-number":["R35GM128717"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Disease reprograms cells through changes in gene regulation, yet identifying these changes remains a major challenge. We introduce NetDes-Duo, a computational method that jointly infers transcription factor regulatory network models for two related conditions using scRNA-seq data. The networks are optimized to have minimal topological differences, while the associated ODE models recapitulate single-cell gene expression trajectories for both conditions. On synthetic benchmarks, NetDes-Duo outperformed methods that infer each network independently. NetDes-Duo was applied to neutrophil reprogramming in naive and tumor-bearing mice, and the network-simulated dynamics reproduced the observed cell state transitions. The naive landscape had two well-separated basins, whereas the tumor-bearing landscape was more continuous, with three shallower basins. Perturbation and driving simulations also identified\n                  <jats:italic>Cebpb<\/jats:italic>\n                  as a key driver of the tumor-bearing transition, consistent with emergency granulopoiesis literature. We expect NetDes-Duo to be a broadly applicable framework for uncovering the regulatory logic of disease-associated cell state transitions.\n                <\/jats:p>","DOI":"10.64898\/2026.09.16.752194","type":"posted-content","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:05:11Z","timestamp":1789733111000},"source":"Crossref","is-referenced-by-count":0,"title":["Joint inference of paired dynamical gene regulatory networks reveals distinct cell-state landscapes of neutrophil reprogramming"],"prefix":"10.64898","author":[{"given":"Alex","family":"Ren","sequence":"first","affiliation":[{"name":"Phillips Exeter Academy, Exeter, NH 03833, USA"},{"name":"Center for Theoretical Biological Physics, Northeastern University, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1002-912X","authenticated-orcid":false,"given":"Yukai","family":"You","sequence":"additional","affiliation":[{"name":"Center for Theoretical Biological Physics, Northeastern University, Boston, MA 02115, USA"},{"name":"Department of Bioengineering, Northeastern University, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2726-114X","authenticated-orcid":false,"given":"Mingyang","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Theoretical Biological Physics, Northeastern University, Boston, MA 02115, USA"},{"name":"Department of Bioengineering, Northeastern University, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092304550564000_2026.09.16.752194v1.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017017108"},{"key":"2026092304550564000_2026.09.16.752194v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/J.CCELL.2020.06.012"},{"key":"2026092304550564000_2026.09.16.752194v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.02.036"},{"key":"2026092304550564000_2026.09.16.752194v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.01.011"},{"key":"2026092304550564000_2026.09.16.752194v1.5","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.3390\/cells11132095","article-title":"Regeneration or Repair? 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