{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T20:02:01Z","timestamp":1784750521385,"version":"3.55.0"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T00:00:00Z","timestamp":1705104000000},"content-version":"vor","delay-in-days":52,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104063"],"award-info":[{"award-number":["82104063"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Top-notch Talent Cultivation Program for Graduate Students of Chongqing Medical University","award":["BJRC202110"],"award-info":[{"award-number":["BJRC202110"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In the drug development process, approximately 30% of failures are attributed to drug safety issues. In particular, the first-in-human (FIH) trial of a new drug represents one of the highest safety risks, and initial dose selection is crucial for ensuring safety in clinical trials. With traditional dose estimation methods, which extrapolate data from animals to humans, catastrophic events have occurred during Phase I clinical trials due to interspecies differences in compound sensitivity and unknown molecular mechanisms. To address this issue, this study proposes a CrossFuse-extreme gradient boosting (XGBoost) method that can directly predict the maximum recommended daily dose of a compound based on existing human research data, providing a reference for FIH dose selection. This method not only integrates multiple features, including molecular representations, physicochemical properties and compound\u2013protein interactions, but also improves feature selection based on cross-validation. The results demonstrate that the CrossFuse-XGBoost method not only improves prediction accuracy compared to that of existing local weighted methods [k-nearest neighbor (k-NN) and variable k-NN (v-NN)] but also solves the low prediction coverage issue of v-NN, achieving full coverage of the external validation set and enabling more reliable predictions. Furthermore, this study offers a high level of interpretability by identifying the importance of different features in model construction. The 241 features with the most significant impact on the maximum recommended daily dose were selected, providing references for optimizing the structure of new compounds and guiding experimental research. The datasets and source code are freely available at https:\/\/github.com\/cqmu-lq\/CrossFuse-XGBoost.<\/jats:p>","DOI":"10.1093\/bib\/bbad511","type":"journal-article","created":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T03:03:17Z","timestamp":1705114997000},"source":"Crossref","is-referenced-by-count":14,"title":["CrossFuse-XGBoost: accurate prediction of the maximum recommended daily dose through multi-feature fusion, cross-validation screening and extreme gradient boosting"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7001-6310","authenticated-orcid":false,"given":"Qiang","family":"Li","sequence":"first","affiliation":[{"name":"Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, Institute of Life Sciences, Chongqing Medical University , Chongqing 400016 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9402-8909","authenticated-orcid":false,"given":"Yu","family":"He","sequence":"additional","affiliation":[{"name":"Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, Institute of Life Sciences, Chongqing Medical University , Chongqing 400016 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6014-8160","authenticated-orcid":false,"given":"Jianbo","family":"Pan","sequence":"additional","affiliation":[{"name":"Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, Institute of Life Sciences, Chongqing Medical University , Chongqing 400016 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,12]]},"reference":[{"key":"2024011303025125300_ref1","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.tips.2019.06.004","article-title":"Advancing drug discovery via artificial intelligence","volume":"40","author":"Chan","year":"2019","journal-title":"Trends Pharmacol Sci"},{"key":"2024011303025125300_ref2","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1001\/jama.2020.1166","article-title":"Estimated research and development investment needed to bring a new medicine to market, 2009\u20132018","volume":"323","author":"Wouters","year":"2020","journal-title":"JAMA"},{"key":"2024011303025125300_ref3","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.drudis.2014.10.011","article-title":"A low-cost, high-quality new drug discovery process using patient-derived induced pluripotent stem cells","volume":"20","author":"Giri","year":"2015","journal-title":"Drug Discov Today"},{"key":"2024011303025125300_ref4","doi-asserted-by":"crossref","first-page":"6423","DOI":"10.1021\/acs.jmedchem.9b01365","article-title":"Dose predictions for drug design","volume":"63","author":"Maurer","year":"2020","journal-title":"J Med Chem"},{"key":"2024011303025125300_ref5","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1200\/PO.20.00379","article-title":"Designing dose-finding phase I clinical trials: top 10 questions that should be discussed with your statistician","volume":"5","author":"Lee","year":"2021","journal-title":"JCO Precis Oncol"},{"key":"2024011303025125300_ref6","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1056\/NEJMoa063842","article-title":"Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412","volume":"355","author":"Suntharalingam","year":"2006","journal-title":"N Engl J Med"},{"key":"2024011303025125300_ref7","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/cpt.2290","article-title":"Safety, tolerability, and pharmacokinetics of FAAH inhibitor BIA 10-2474: a double-blind, randomized, placebo-controlled study in healthy volunteers","volume":"111","author":"Rocha","year":"2022","journal-title":"Clin Pharmacol Ther"},{"key":"2024011303025125300_ref8","article-title":"Lessons from the fatal French study BIA-10-2474","volume":"353","author":"Moore","year":"2016","journal-title":"BMJ"},{"key":"2024011303025125300_ref9","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.1111\/febs.13754","article-title":"The rise and fall of the CD 28 superagonist TGN 1412 and its return as TAB 08: a personal account","volume":"283","author":"H\u00fcnig","year":"2016","journal-title":"FEBS J"},{"key":"2024011303025125300_ref10","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1007\/s00228-020-02924-x","article-title":"First-in-human dose: current status review for better future perspectives","volume":"76","author":"Mishra","year":"2020","journal-title":"Eur J Clin Pharmacol"},{"key":"2024011303025125300_ref11","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2174\/1570163043484789","article-title":"Assessment of the health effects of chemicals in humans: I. 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