{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:20:51Z","timestamp":1787674851768,"version":"build-2784847793"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"NSERC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Intelligent Systems"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>Single\u2010molecule localization microscopy (SMLM) achieves nanoscale imaging of complex protein structures in the cell. However, the ability to capture structural variability across cell conditions (cell lines, gene expression, treatment) from 3D point cloud SMLM data remains limited. We present siMILe, a weakly supervised multiple instance learning machine learning method to close this gap in interpretable subcellular discovery. siMILe identifies condition\u2010specific changes in protein assemblies by leveraging their shape and network features, without requiring structure\u2010level supervision. siMILe improves structure classification by extending embedded instance selection through adversarial erasing and a symmetric classifier. We validated siMILe by detecting caveolae from caveolin\u20101 (Cav1) labeled PC3 prostate cancer cells differentially expressing cavin\u20101. In PC3\u2010CAVIN1 cells, cavin\u20101 closely associates with siMILe\u2010identified caveolae, to a lesser extent with higher\u2010order noncaveolar Cav1 scaffolds, but not small Cav1 oligomers corresponding to 8S complexes, supporting a role for progressive cavin\u20101 interaction in 8S complex oligomerization. We also validated siMILe on simulated SMLM data and in detecting inhibitor\u2010induced structural variations within clathrin\u2010coated pit data. These results highlight siMILe's potential to identify differential molecular structures in distinct cell conditions. siMILe extends the SuperResNET SMLM software platform with the ability to detect interpretable structural differences across conditions.<\/jats:p>","DOI":"10.1002\/aisy.202501159","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:09:46Z","timestamp":1777536586000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adversarial Erasing Enhanced Multiple Instance Learning (siMILe): Discriminative Identification of Oligomeric Protein Structures in Single Molecule Localization Microscopy"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-7879","authenticated-orcid":false,"given":"Christian","family":"Hallgrimson","sequence":"first","affiliation":[{"name":"School of Computing Science Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5975-6896","authenticated-orcid":false,"given":"Y. 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