{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:48:23Z","timestamp":1792784903629,"version":"4.5.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":79,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Aligning Science Across Parkinson\u2019s","id":[{"id":"https:\/\/ror.org\/03zj4c476","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Parkinsons Dis."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mitochondrial and lysosomal dysfunction are central features of Parkinson\u2019s disease (PD) across major genetic forms including\n                    <jats:italic>PRKN<\/jats:italic>\n                    ,\n                    <jats:italic>SNCA<\/jats:italic>\n                    , and\n                    <jats:italic>LRRK2<\/jats:italic>\n                    . We applied\n                    <jats:italic>cell morphomics<\/jats:italic>\n                    , a machine-learning-based framework combining high-content imaging with quantitative feature extraction, to analyse mitochondrial and lysosomal morphology at single-cell resolution in iPS cell-derived cortical neurons from PD patients and healthy controls (13 lines total). Supervised machine-learning models distinguished PD neurons from controls with high accuracy (AUC\u2009=\u20090.87) and reliably separated individual genotypes. Feature importance and attribution analysis revealed genotype-specific organelle biases in the relative contribution of mitochondrial and lysosomal features, with mitochondrial features dominating classification in\n                    <jats:italic>PRKN<\/jats:italic>\n                    neurons, balanced mitochondrial and lysosomal contributions in\n                    <jats:italic>SNCA<\/jats:italic>\n                    neurons, and a greater lysosomal contribution in\n                    <jats:italic>LRRK2<\/jats:italic>\n                    neurons. Multi-class models retained strong performance, and findings were reproduced across two independent laboratories using different dyes and imaging conditions. These results demonstrate that morphomics provides a robust and scalable framework to quantify genotype-specific organelle abnormalities in PD neurons and supports its application for cellular stratification and biomarker discovery.\n                  <\/jats:p>","DOI":"10.1038\/s41531-026-01458-w","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T18:03:31Z","timestamp":1785607411000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Machine learning image analysis predicts Parkinson disease genotype and mitochondrial lysosomal abnormalities in iPS neurons"],"prefix":"10.1038","volume":"12","author":[{"given":"Yan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7473-8640","authenticated-orcid":false,"given":"Maximilian","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7985-5148","authenticated-orcid":false,"given":"Jessica","family":"Chedid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1287-4007","authenticated-orcid":false,"given":"Ratneswary","family":"Sutharsan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adahir","family":"Labrador-Garrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2687-3526","authenticated-orcid":false,"given":"Dad","family":"Abu-Bonsrah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2890-7021","authenticated-orcid":false,"given":"Chiara","family":"Pavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4395-5830","authenticated-orcid":false,"given":"Tyra","family":"Fraser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9603-8385","authenticated-orcid":false,"given":"Dmitry","family":"Ovchinnikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0512-8989","authenticated-orcid":false,"given":"Ryan","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9234-3243","authenticated-orcid":false,"given":"Dario","family":"Strbenac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4867-9230","authenticated-orcid":false,"given":"Jennifer A.","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2632-0304","authenticated-orcid":false,"given":"Lachlan H.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1360-1265","authenticated-orcid":false,"given":"Deniz","family":"Kirik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8212-9884","authenticated-orcid":false,"given":"Clare L.","family":"Parish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0422-8398","authenticated-orcid":false,"given":"Glenda M.","family":"Halliday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1255-3617","authenticated-orcid":false,"given":"Carolyn M.","family":"Sue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9121-0294","authenticated-orcid":false,"given":"Nicolas","family":"Dzamko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2961-3954","authenticated-orcid":false,"given":"Gautam","family":"Wali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"1458_CR1","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","volume":"397","author":"BR Bloem","year":"2021","unstructured":"Bloem, B. 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