{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T01:01:49Z","timestamp":1768352509809,"version":"3.49.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T00:00:00Z","timestamp":1518048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"publisher","award":["81771478"],"award-info":[{"award-number":["81771478"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"publisher","award":["61571233"],"award-info":[{"award-number":["61571233"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018615","name":"University Science Research Project of Jiangsu Province","doi-asserted-by":"crossref","award":["17KJA510003"],"award-info":[{"award-number":["17KJA510003"]}],"id":[{"id":"10.13039\/501100018615","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI1564756"],"award-info":[{"award-number":["DBI1564756"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Precise assessment of ligand bioactivities (including IC50, EC50, Ki, Kd, etc.) is essential for virtual screening and lead compound identification. However, not all ligands have experimentally determined activities. In particular, many G protein-coupled receptors (GPCRs), which are the largest integral membrane protein family and represent targets of nearly 40% drugs on the market, lack published experimental data about ligand interactions. Computational methods with the ability to accurately predict the bioactivity of ligands can help efficiently address this problem.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We proposed a new method, WDL-RF, using weighted deep learning and random forest, to model the bioactivity of GPCR-associated ligand molecules. The pipeline of our algorithm consists of two consecutive stages: (i) molecular fingerprint generation through a new weighted deep learning method, and (ii) bioactivity calculations with a random forest model; where one uniqueness of the approach is that the model allows end-to-end learning of prediction pipelines with input ligands being of arbitrary size. The method was tested on a set of twenty-six non-redundant GPCRs that have a high number of active ligands, each with 200\u20134000 ligand associations. The results from our benchmark show that WDL-RF can generate bioactivity predictions with an average root-mean square error 1.33 and correlation coefficient (r2) 0.80 compared to the experimental measurements, which are significantly more accurate than the control predictors with different molecular fingerprints and descriptors. In particular, data-driven molecular fingerprint features, as extracted from the weighted deep learning models, can help solve deficiencies stemming from the use of traditional hand-crafted features and significantly increase the efficiency of short molecular fingerprints in virtual screening.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The WDL-RF web server, as well as source codes and datasets of WDL-RF, is freely available at https:\/\/zhanglab.ccmb.med.umich.edu\/WDL-RF\/ for academic purposes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty070","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T12:09:55Z","timestamp":1518005395000},"page":"2271-2282","source":"Crossref","is-referenced-by-count":44,"title":["WDL-RF: predicting bioactivities of ligand molecules acting with G protein-coupled receptors by combining weighted deep learning and random forest"],"prefix":"10.1093","volume":"34","author":[{"given":"Jiansheng","family":"Wu","sequence":"first","affiliation":[{"name":"School of Geographic and Biological Information, Nanjing University of Posts and Telecommunications, Nanjing, China"},{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuming","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Telecommunication and Information Engineering, Nanjing University of Posts and Telecommunications, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijian","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Computer and Information, Hohai University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Pang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haifeng","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Telecommunication and Information Engineering, Nanjing University of Posts and Telecommunications, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wallace K B","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan, Ann Arbor, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Ke","sequence":"additional","affiliation":[{"name":"Child Mental Health Research Center, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, USA"},{"name":"Department of Biological Chemistry, University of Michigan, Ann Arbor, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,2,8]]},"reference":[{"key":"2023051604095943000_bty070-B1","doi-asserted-by":"crossref","first-page":"46.","DOI":"10.1186\/1471-2156-8-46","article-title":"Variation in the gene coding for the M5 Muscarinic receptor (CHRM5) influences cigarette dose but is not associated with dependence to drugs of addiction: evidence from a prospective population based cohort study of young adults","volume":"8","author":"Anney","year":"2007","journal-title":"BMC Genet"},{"key":"2023051604095943000_bty070-B2","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.freeradbiomed.2005.09.015","article-title":"Inhibition of sphingosine-1-phosphate- and vascular endothelial growth factor-induced endothelial cell chemotaxis by red grape skin polyphenols correlates with a decrease in early platelet-activating factor synthesis","volume":"40","author":"Barthomeuf","year":"2006","journal-title":"Free Radic. 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