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Here we introduce SIGMA (SIgnaling via Golgi Morphology Analysis), a framework that reframes pathway identification as a morphological classification problem centered on the Golgi apparatus. SIGMA integrates imaging flow cytometry for population-scale Golgi profiling, teacher-student knowledge distillation to transfer fine morphological cues from limited high-resolution images to an efficient lower-resolution classifier, and mechanistic generalization testing with chemically distinct activators. Applied to MRC-5 fibroblasts across six conditions spanning four signaling cascades plus controls, SIGMA achieved 90.02% cell-level accuracy and correctly assigned five of seven structurally unrelated external compounds to their expected pathway class. These results establish Golgi morphology as a multiplexed, machine-readable fingerprint of signaling state.<\/jats:p>","DOI":"10.64898\/2026.10.01.756010","type":"posted-content","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:35:12Z","timestamp":1790976912000},"source":"Crossref","is-referenced-by-count":0,"title":["SIGMA: SIgnaling via Golgi Morphology Analysis for pathway-state classification"],"prefix":"10.64898","author":[{"given":"Mengchen","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Computer Science, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Division of Molecular and Translational Biomedicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baocheng","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pulin","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Division of Molecular and Translational Biomedicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100708200646000_2026.10.01.756010v1.1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2018.7534"},{"key":"2026100708200646000_2026.10.01.756010v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2023.102293"},{"key":"2026100708200646000_2026.10.01.756010v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13567"},{"key":"2026100708200646000_2026.10.01.756010v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0210-7"},{"key":"2026100708200646000_2026.10.01.756010v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2220"},{"key":"2026100708200646000_2026.10.01.756010v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-55825-x"},{"key":"2026100708200646000_2026.10.01.756010v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2025.101229"},{"key":"2026100708200646000_2026.10.01.756010v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108657"},{"key":"2026100708200646000_2026.10.01.756010v1.9","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005314"},{"key":"2026100708200646000_2026.10.01.756010v1.10","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.076455"},{"key":"2026100708200646000_2026.10.01.756010v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2012.59"},{"key":"2026100708200646000_2026.10.01.756010v1.12","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200912082"},{"key":"2026100708200646000_2026.10.01.756010v1.13","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00421"},{"key":"2026100708200646000_2026.10.01.756010v1.14","doi-asserted-by":"publisher","DOI":"10.1100\/2012\/498278"},{"key":"2026100708200646000_2026.10.01.756010v1.15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2009.01007.x"},{"key":"2026100708200646000_2026.10.01.756010v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.100952"},{"key":"2026100708200646000_2026.10.01.756010v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2669"},{"key":"2026100708200646000_2026.10.01.756010v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/nrm931"},{"key":"2026100708200646000_2026.10.01.756010v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2022.106959"},{"key":"2026100708200646000_2026.10.01.756010v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2020.103693"},{"key":"2026100708200646000_2026.10.01.756010v1.21","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202208005"},{"key":"2026100708200646000_2026.10.01.756010v1.22","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E17-06-0379"},{"key":"2026100708200646000_2026.10.01.756010v1.23","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202503083"},{"key":"2026100708200646000_2026.10.01.756010v1.24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005612"},{"key":"2026100708200646000_2026.10.01.756010v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75899-5"},{"key":"2026100708200646000_2026.10.01.756010v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0403-1"},{"key":"2026100708200646000_2026.10.01.756010v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00117-w"},{"key":"2026100708200646000_2026.10.01.756010v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-01018-x"},{"key":"2026100708200646000_2026.10.01.756010v1.29","unstructured":"Hinton, G. , Vinyals, O. & Dean, J. 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