{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:58:00Z","timestamp":1768568280771,"version":"3.49.0"},"posted":{"date-parts":[[2025,3,12]]},"group-title":"Genetic and Genomic Medicine","reference-count":23,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Deep learning (DL) is increasingly used to analyze medical imaging, but is less refined for rare conditions, which require novel pre-processing and analytical approaches. To assess DL in the context of rare diseases, we focused on alkaptonuria (AKU), a rare disorder that affects the spine and involves other sequelae; treatments include the medication nitisinone. Since assessing X-rays to determine disease severity can be a slow, manual process requiring considerable expertise, we aimed to determine whether our DL methods could accurately identify overall spine severity, severity at specific regions of the spine, and whether DL could detect whether patients were receiving nitisinone. We evaluated DL performance versus clinical experts using cervical and lumbar spine radiographs. DL models predicted global severity scores (30-point scale) within 1.72 \u00b1 1.96 points of expert clinician scores for cervical and 2.51 \u00b1 1.96 points for lumbar radiographs. For region-specific metrics, we assessed the degree of narrowing, calcium, and vacuum phenomena at each intervertebral space (IVS). Our model\u2019s narrowing scores were within 0.191-0.557 points from clinician scores (6-point scale), calcium was predicted with 78\u201390% accuracy (present, absent, or disc fusion), while vacuum disc phenomenon predictions were less consistent (41\u201390%). Intriguingly, DL models predicted nitisinone treatment status with 68\u201377% accuracy, while expert clinicians appeared unable to discern nitisinone status (51% accuracy) (p = 2.0 \u00d7 10\n                  <jats:sup>-9<\/jats:sup>\n                  ). This highlights the potential for DL to augment certain types of clinical assessments in rare disease, as well as identifying occult features like treatment status.\n                <\/jats:p>","DOI":"10.1101\/2025.03.11.25323762","type":"posted-content","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T12:54:24Z","timestamp":1741870464000},"source":"Crossref","is-referenced-by-count":0,"title":["Deep Learning Study of Alkaptonuria Spinal Disease Assesses Global and Regional Severity and Detects Occult Treatment Status"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9473-1354","authenticated-orcid":false,"given":"Kendall A.","family":"Flaharty","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vibha","family":"Chandrasekar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene J.","family":"Castillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dat","family":"Duong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2697-1046","authenticated-orcid":false,"given":"Carlos R.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanna Ledgister","family":"Hanchard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebekah L.","family":"Waikel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Rossignol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy J.","family":"Introne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin D.","family":"Solomon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025032002554492000_2025.03.11.25323762v1.1","article-title":"How to build the best medical image segmentation algorithm using foundation models: a comprehensive empirical study with Segment Anything Model","year":"2024","journal-title":"arXiv 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Metabolic Disease"},{"key":"2025032002554492000_2025.03.11.25323762v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.04.016"},{"key":"2025032002554492000_2025.03.11.25323762v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2019.06.006"},{"key":"2025032002554492000_2025.03.11.25323762v1.14","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1080\/14397595.2020.1764744","article-title":"Comprehensive review on intravertebral intraspinal, intrajoint, and intradiscal vacuum phenomenon: From anatomy and physiology to pathology","volume":"31","year":"2021","journal-title":"Modern Rheumatology"},{"key":"2025032002554492000_2025.03.11.25323762v1.15","doi-asserted-by":"crossref","first-page":"10286","DOI":"10.1038\/s41598-021-89743-x","article-title":"Predicting sex from retinal fundus photographs using automated deep learning","volume":"11","year":"2021","journal-title":"Scientific 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