{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T21:26:34Z","timestamp":1776893194394,"version":"3.51.2"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-006960"],"award-info":[{"award-number":["INV-006960"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Malaria which is mainly caused by <jats:italic>Plasmodium falciparum<\/jats:italic> parasite remains a devastating public health concern, necessitating the need to develop new antimalarial agents. <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> heat shock protein 90 (Hsp90), is indispensable for parasite survival and a promising drug target. Inhibitors targeting the ATP-binding pocket of the N-terminal domain have anti-<jats:italic>Plasmodium<\/jats:italic> effects. We proposed a <jats:italic>de novo<\/jats:italic> active learning (AL) driven method in tandem with docking to predict inhibitors with unique scaffolds and preferential selectivity towards PfHsp90. Reference compounds, predicted to bind PfHsp90 at the ATP-binding pocket and possessing anti-<jats:italic>Plasmodium<\/jats:italic> activities, were used to generate 10,000 unique derivatives and to build the Auto-quantitative structures activity relationships (QSAR) models. Glide docking was performed to predict the docking scores of the derivatives and &gt; 15,000 compounds obtained from the ChEMBL database. Re-iterative training and testing of the models was performed until the optimum Kennel-based Partial Least Square (KPLS) regression model with a regression coefficient R2 = 0.75 for the training set and squared correlation prediction Q2 = 0.62 for the test set reached convergence. Rescoring using induced fit docking and molecular dynamics simulations enabled us to prioritize 15 ATP\/ADP-like design ideas for purchase. The compounds exerted moderate activity towards <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> NF54 strain with IC<jats:sub>50<\/jats:sub> values of \u2264 6\u03bcM and displayed moderate to weak affinity towards PfHsp90 (K<jats:sub>D<\/jats:sub> range: 13.5\u201319.9\u03bcM) comparable to the reported affinity of ADP. The most potent compound was FTN-T5 (PfN54 IC<jats:sub>50<\/jats:sub>:1.44\u03bcM; HepG2\/CHO cells SI\u2265 29) which bound to PfHsp90 with moderate affinity (K<jats:sub>D<\/jats:sub>:7.7\u03bcM), providing a starting point for optimization efforts. Our work demonstrates the great utility of AL for the rapid identification of novel molecules for drug discovery (i.e., hit identification). The potency of FTN-T5 will be critical for designing species-selective inhibitors towards developing more efficient agents against malaria.<\/jats:p>","DOI":"10.1371\/journal.pone.0308969","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T18:28:27Z","timestamp":1732559307000},"page":"e0308969","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Auto QSAR-based active learning docking for hit identification of potential inhibitors of Plasmodium falciparum Hsp90 as antimalarial agents"],"prefix":"10.1371","volume":"19","author":[{"given":"Thato","family":"Matlhodi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisema Patrick","family":"Makatsela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tendamudzimu Harmfree","family":"Dongola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mthokozisi Blessing Cedric","family":"Simelane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Addmore","family":"Shonhai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4213-5416","authenticated-orcid":true,"given":"Njabulo Joyfull","family":"Gumede","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0864-9157","authenticated-orcid":true,"given":"Fortunate","family":"Mokoena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"pone.0308969.ref001","unstructured":"Organization WH. World malaria World malaria report report. 2023."},{"issue":"8","key":"pone.0308969.ref002","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nm.4381","article-title":"Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic","volume":"23","author":"B Blasco","year":"2017","journal-title":"Nat Med"},{"issue":"5","key":"pone.0308969.ref003","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1093\/bfgp\/elz008","article-title":"The genomic architecture of antimalarial drug resistance","volume":"18","author":"AN Cowell","year":"2019","journal-title":"Brief Funct Genomics"},{"issue":"10","key":"pone.0308969.ref004","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/s41591-020-1005-2","article-title":"Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda","volume":"26","author":"A Uwimana","year":"2020","journal-title":"Nat Med"},{"issue":"5","key":"pone.0308969.ref005","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1314981","article-title":"Spread of artemisinin resistance in Plasmodium falciparum malaria","volume":"371","author":"EA Ashley","year":"2014","journal-title":"N Engl J Med"},{"issue":"1","key":"pone.0308969.ref006","doi-asserted-by":"crossref","first-page":"11901","DOI":"10.1038\/ncomms11901","article-title":"A broad analysis of resistance development in the malaria parasite","volume":"7","author":"VC Corey","year":"2016","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0308969.ref007","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1574-695X.2009.00639.x","article-title":"Plasmodial heat shock proteins: targets for chemotherapy","volume":"58","author":"A. Shonhai","year":"2010","journal-title":"FEMS Immunol Med Microbiol"},{"issue":"2","key":"pone.0308969.ref008","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.molbiopara.2007.01.009","article-title":"Chaperoning a cellular upheaval in malaria: heat shock proteins in Plasmodium falciparum","volume":"153","author":"P Acharya","year":"2007","journal-title":"Mol Biochem Parasitol"},{"issue":"6388","key":"pone.0308969.ref009","doi-asserted-by":"crossref","DOI":"10.1126\/science.aap7847","article-title":"Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis","volume":"360","author":"M Zhang","year":"2018","journal-title":"Science"},{"issue":"1","key":"pone.0308969.ref010","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0378-1119(94)90661-0","article-title":"Sequence, transcript characterization and polymorphisms of a Plasmodium falciparum gene belonging to the heat-shock protein (HSP) 90 family","volume":"151","author":"X Su","year":"1994","journal-title":"Gene"},{"key":"pone.0308969.ref011","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1475-2875-2-30","article-title":"The heat shock protein 90 of Plasmodium falciparum and antimalarial activity of its inhibitor, geldanamycin","volume":"2","author":"R Kumar","year":"2003","journal-title":"Malar J"},{"issue":"20","key":"pone.0308969.ref012","doi-asserted-by":"crossref","first-page":"18336","DOI":"10.1074\/jbc.M211309200","article-title":"Heat Shock Protein 90 Function Is Essential for Plasmodium falciparum Growth in Human Erythrocytes*","volume":"278","author":"G Banumathy","year":"2003","journal-title":"J Biol Chem"},{"issue":"4","key":"pone.0308969.ref013","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01799-17","article-title":"Identification of Hsp90 Inhibitors with Anti-Plasmodium Activity","volume":"62","author":"D Posfai","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pone.0308969.ref014","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/1475-2875-9-236","article-title":"Chaperone expression profiles correlate with distinct physiological states of Plasmodium falciparum in malaria patients","volume":"9","author":"R Pallavi","year":"2010","journal-title":"Malar J"},{"key":"pone.0308969.ref015","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/128_2012_356","article-title":"Hsp90: structure and function","volume":"328","author":"SE Jackson","year":"2013","journal-title":"Top Curr Chem"},{"issue":"1\u20133","key":"pone.0308969.ref016","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0014-5793(04)00229-7","article-title":"Hsp90 isoforms: functions, expression and clinical importance","volume":"562","author":"AS Sreedhar","year":"2004","journal-title":"FEBS Lett"},{"issue":"49","key":"pone.0308969.ref017","doi-asserted-by":"crossref","first-page":"37964","DOI":"10.1074\/jbc.M110.155317","article-title":"Heat Shock Protein 90 as a Drug Target against Protozoan Infections BIOCHEMICAL CHARACTERIZATION OF HSP90 FROM PLASMODIUM FALCIPARUM AND TRYPANOSOMA EVANSI AND EVALUATION OF ITS INHIBITOR AS A CANDIDATE DRUG *","volume":"285","author":"R Pallavi","year":"2010","journal-title":"J Biol Chem"},{"issue":"9","key":"pone.0308969.ref018","doi-asserted-by":"crossref","first-page":"e75446","DOI":"10.1371\/journal.pone.0075446","article-title":"A purine analog synergizes with chloroquine (CQ) by targeting Plasmodium falciparum Hsp90 (PfHsp90)","volume":"8","author":"D Shahinas","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"pone.0308969.ref019","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s12936-017-1940-7","article-title":"Identification and characterization of the antiplasmodial activity of Hsp90 inhibitors","volume":"16","author":"C Murillo-Solano","year":"2017","journal-title":"Malar J"},{"issue":"8","key":"pone.0308969.ref020","doi-asserted-by":"crossref","first-page":"4207","DOI":"10.1128\/AAC.00328-12","article-title":"Harmine is a potent antimalarial targeting Hsp90 and synergizes with chloroquine and artemisinin","volume":"56","author":"D Shahinas","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"pone.0308969.ref021","first-page":"143","article-title":"Intracellular Protozoan Parasites of Humans: The Role of Molecular Chaperones in Development and Pathogenesis","author":"A Shonhai","year":"2011","journal-title":"Science (80-)"},{"issue":"21","key":"pone.0308969.ref022","doi-asserted-by":"crossref","first-page":"127502","DOI":"10.1016\/j.bmcl.2020.127502","article-title":"Antimalarial activity of tetrahydro-\u03b2-carbolines targeting the ATP binding pocket of the Plasmodium falciparum heat shock 90 protein","volume":"30","author":"S Eagon","year":"2020","journal-title":"Bioorganic & Med Chem Lett"},{"issue":"8","key":"pone.0308969.ref023","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1002\/ejoc.201301580","article-title":"Microwave-Assisted Synthesis of Tetrahydro-\u03b2-carbolines and \u03b2-Carbolines","volume":"2014","author":"S Eagon","year":"2014","journal-title":"European J Org Chem"},{"issue":"1","key":"pone.0308969.ref024","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1186\/s12936-016-1625-7","article-title":"In vitro and in vivo anti-malarial activity of novel harmine-analog heat shock protein 90 inhibitors: a possible partner for artemisinin","volume":"15","author":"AG Bayih","year":"2016","journal-title":"Malar J"},{"issue":"6","key":"pone.0308969.ref025","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.1021\/jm401801t","article-title":"Differences in conformational dynamics between Plasmodium falciparum and human Hsp90 orthologues enable the structure-based discovery of pathogen-selective inhibitors","volume":"57","author":"T Wang","year":"2014","journal-title":"J Med Chem"},{"issue":"13","key":"pone.0308969.ref026","doi-asserted-by":"crossref","first-page":"6344","DOI":"10.1021\/acs.jmedchem.6b00591","article-title":"Inhibition of Plasmodium falciparum Hsp90 Contributes to the Antimalarial Activities of Aminoalcohol-carbazoles","volume":"59","author":"T Wang","year":"2016","journal-title":"J Med Chem"},{"key":"pone.0308969.ref027","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jmgm.2018.11.017","article-title":"In silico identification and evaluation of potential interaction of Azadirachta indica phytochemicals with Plasmodium falciparum heat shock protein 90","volume":"87","author":"MO Daniyan","year":"2019","journal-title":"J Mol Graph Model"},{"key":"pone.0308969.ref028","doi-asserted-by":"crossref","first-page":"127818","DOI":"10.1016\/j.bmcl.2021.127818","article-title":"Identification of Plasmodium falciparum heat shock 90 inhibitors via molecular docking","volume":"35","author":"N Everson","year":"2021","journal-title":"Bioorg Med Chem Lett"},{"key":"pone.0308969.ref029","article-title":"Pharmacophore Model-Based Virtual Screening Workflow for Discovery of Inhibitors Targeting Plasmodium falciparum Hsp90","author":"O Mafethe","year":"2023","journal-title":"ACS Omega"},{"issue":"9","key":"pone.0308969.ref030","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1080\/17460441.2021.1909567","article-title":"Artificial intelligence in drug discovery: recent advances and future perspectives","volume":"16","author":"J Jim\u00e9nez-Luna","year":"2021","journal-title":"Expert Opin Drug Discov"},{"issue":"7","key":"pone.0308969.ref031","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1021\/acs.jcim.3c01661","article-title":"Regression-Based Active Learning for Accessible Acceleration of Ultra-Large Library Docking","volume":"64","author":"E Marin","year":"2024","journal-title":"J Chem Inf Model"},{"key":"pone.0308969.ref032","unstructured":"Schr\u00f6dinger Release 2021\u20132. Maestro. Maestro. 2021;Schr\u00f6dinge(LLC):New York, NY."},{"issue":"13","key":"pone.0308969.ref033","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.1002\/prot.22799","article-title":"Structure of the ATP-binding domain of Plasmodium falciparum Hsp90","volume":"78","author":"KD Corbett","year":"2010","journal-title":"Proteins"},{"key":"pone.0308969.ref034","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0092-8674(00)80203-2","article-title":"Crystal Structure of an Hsp90 \u2013Geldanamycin Complex: Targeting of a Protein Chaperone by an Antitumor Agent","volume":"89","author":"CE Stebbins","year":"1997","journal-title":"Cell"},{"issue":"4","key":"pone.0308969.ref035","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1083\/jcb.143.4.901","article-title":"In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis","volume":"143","author":"WM Obermann","year":"1998","journal-title":"J Cell Biol"},{"key":"pone.0308969.ref036","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"HM Berman","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"pone.0308969.ref037","unstructured":"Schr\u00f6dinger Release 2021\u20133. Protein Preparation Wizard; Epik, Schr\u00f6dinger, LLC, New York, NY, 2021. Impact, Schr\u00f6dinger. 2021;Prime, Sch(New York, NY):LLC."},{"key":"pone.0308969.ref038","unstructured":"Schr\u00f6dinger Release 2021\u20132. Glide. Schr\u00f6dinger. 2021;LLC(New York, NY)."},{"key":"pone.0308969.ref039","unstructured":"Schr\u00f6dinger Release 2021\u20133. LigPrep. LigPrep. 2021;Schr\u00f6dinge(LLC):New York, NY."},{"issue":"1","key":"pone.0308969.ref040","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1021\/acs.jcim.2c01136","article-title":"Pathfinder\u2500Navigating and Analyzing Chemical Reaction Networks with an Efficient Graph-Based Approach","volume":"63","author":"PL T\u00fcrtscher","year":"2023","journal-title":"J Chem Inf Model"},{"issue":"6","key":"pone.0308969.ref041","doi-asserted-by":"crossref","DOI":"10.3390\/ph13060111","article-title":"Novel 1,2,4-Oxadiazole Derivatives in Drug Discovery","volume":"13","author":"K Biernacki","year":"2020","journal-title":"Pharmaceuticals (Basel)"},{"issue":"23","key":"pone.0308969.ref042","doi-asserted-by":"crossref","DOI":"10.3390\/molecules27238569","article-title":"Pathfinder-Driven Chemical Space Exploration and Multiparameter Optimization in Tandem with Glide\/IFD and QSAR-Based Active Learning Approach to Prioritize Design Ideas for FEP+ Calculations of SARS-CoV-2 PL(pro) Inhibitors","volume":"27","author":"NJ Gumede","year":"2022","journal-title":"Molecules"},{"issue":"9","key":"pone.0308969.ref043","doi-asserted-by":"crossref","first-page":"3782","DOI":"10.1021\/acs.jcim.9b00367","article-title":"Reaction-Based Enumeration, Active Learning, and Free Energy Calculations To Rapidly Explore Synthetically Tractable Chemical Space and Optimize Potency of Cyclin-Dependent Kinase 2 Inhibitors","volume":"59","author":"KD Konze","year":"2019","journal-title":"J Chem Inf Model"},{"issue":"15","key":"pone.0308969.ref044","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.4155\/fmc-2016-0093","article-title":"AutoQSAR: an automated machine learning tool for best-practice quantitative structure-activity relationship modeling","volume":"8","author":"SL Dixon","year":"2016","journal-title":"Future Med Chem"},{"key":"pone.0308969.ref045","doi-asserted-by":"crossref","unstructured":"Bowers KJ, Chow DE, Xu H, Dror RO, Eastwood MP, Gregersen BA, et al. Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters. In: SC \u201806: Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing. 2006. p. 43.","DOI":"10.1109\/SC.2006.54"},{"issue":"4","key":"pone.0308969.ref046","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1080\/07391102.2020.1734092","article-title":"In silico search of triple mutant T790M\/C797S allosteric inhibitors to conquer acquired resistance problem in non-small cell lung cancer (NSCLC): a combined approach of structure-based virtual screening and molecular dynamics simulation","volume":"39","author":"HM Patel","year":"2021","journal-title":"J Biomol Struct Dyn"},{"issue":"5","key":"pone.0308969.ref047","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"S Genheden","year":"2015","journal-title":"Expert Opin Drug Discov"},{"issue":"6","key":"pone.0308969.ref048","doi-asserted-by":"crossref","first-page":"739","DOI":"10.4269\/ajtmh.1993.48.739","article-title":"Parasite lactate dehydrogenase as an assay for Plasmodium falciparum drug sensitivity","volume":"48","author":"MT Makler","year":"1993","journal-title":"Am J Trop Med Hyg"},{"issue":"1\u20132","key":"pone.0308969.ref049","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"T. Mosmann","year":"1983","journal-title":"J Immunol Methods"},{"key":"pone.0308969.ref050","doi-asserted-by":"crossref","first-page":"947203","DOI":"10.3389\/fmolb.2022.947203","article-title":"Inhibition of Plasmodium falciparum Hsp70-Hop partnership by 2-phenylthynesulfonamide","volume":"9","author":"T Muthelo","year":"2022","journal-title":"Front Mol Biosci"},{"issue":"4","key":"pone.0308969.ref051","doi-asserted-by":"crossref","first-page":"187","DOI":"10.4103\/2229-3485.192046","article-title":"Common pitfalls in statistical analysis: The use of correlation techniques","volume":"7","author":"R Aggarwal","year":"2016","journal-title":"Perspect Clin Res"},{"issue":"3","key":"pone.0308969.ref052","doi-asserted-by":"crossref","first-page":"e0119264","DOI":"10.1371\/journal.pone.0119264","article-title":"Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis","volume":"10","author":"L. Mart\u00ednez","year":"2015","journal-title":"PLoS One"},{"issue":"17","key":"pone.0308969.ref053","doi-asserted-by":"crossref","first-page":"11122","DOI":"10.1021\/acsomega.1c00485","article-title":"Enthalpy\u2014Entropy Compensation in Biomolecular Recognition: A Computational Perspective","volume":"6","author":"F Peccati","year":"2021","journal-title":"ACS Omega"},{"issue":"4","key":"pone.0308969.ref054","doi-asserted-by":"crossref","first-page":"660","DOI":"10.2174\/1386207324666210308110646","article-title":"Water Mapping and Scoring Approaches to Predict the Role of Hydration Sites in the Binding Affinity of PAK1 Inhibitors","volume":"25","author":"J Biswal","year":"2022","journal-title":"Comb Chem High Throughput Screen"},{"issue":"4","key":"pone.0308969.ref055","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1021\/acs.jctc.1c00136","article-title":"Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein\u2014Ligand Binding","volume":"17","author":"EB Miller","year":"2021","journal-title":"J Chem Theory Comput"},{"key":"pone.0308969.ref056","unstructured":"World Health Organization. World Malaria Report. Vol. WHO\/HTM\/GM, World Health Organization. 2021. 238 p."},{"issue":"3","key":"pone.0308969.ref057","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/s41596-021-00659-2","article-title":"Artificial intelligence\u2014enabled virtual screening of ultra-large chemical libraries with deep docking","volume":"17","author":"F Gentile","year":"2022","journal-title":"Nat Protoc"},{"issue":"1","key":"pone.0308969.ref058","doi-asserted-by":"crossref","first-page":"7065","DOI":"10.1038\/s41467-021-26703-z","article-title":"A deep learning framework identifies dimensional representations of Alzheimer\u2019s Disease from brain structure","volume":"12","author":"Z Yang","year":"2021","journal-title":"Nat Commun"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0308969","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T18:28:46Z","timestamp":1732559326000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0308969"}},"subtitle":[],"editor":[{"given":"Yash","family":"Gupta","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,25]]},"references-count":58,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0308969","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,25]]}}}