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image of Revolutionizing Patient Safety: Machine Learning and AI for the Early Detection of Adverse Drug Reactions and Drug-Induced Toxicity

Abstract

Adverse drug reactions and drug-induced toxicity provide significant issues in drug research, jeopardizing patient safety and driving up healthcare costs. Toxicity has a greater potential impact than infectious diseases since it is less visible. Early diagnosis of these difficulties is critical to determining a drug's safety and viability profile. The combination of machine learning and artificial intelligence has marked a watershed moment in the identification of early adverse drug reactions and toxicity. These computational approaches enable rapid, extensive, and precise prediction of likely adverse drug reactions and toxicity even before practical drug manufacture, preclinical testing, and clinical trials. This paradigm change strives to create more efficient and safe drugs, lowering the likelihood of drug withdrawal. This comprehensive review investigates the critical role of machine learning and artificial intelligence in quickly detecting adverse drug reactions and toxicity, including approaches from data mining to deep learning. It lists essential databases, modelling techniques, and software that may be used to model and predict a wide range of toxicities and adverse drug reactions. This review provides a comprehensive overview, outlining recent developments and projecting future opportunities in machine learning and artificial intelligence-driven rapid identification of adverse drug reactions and drug-induced toxicity. It highlights the capabilities of these technologies and their enormous potential to improve patient safety and revolutionize medication discovery.

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2024-10-21
2024-11-22
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References

  1. DiMasi J.A. Grabowski H.G. Hansen R.W. Innovation in the pharmaceutical industry: New estimates of R&D costs. J. Health Econ. 2016 47 20 33 10.1016/j.jhealeco.2016.01.012 26928437
    [Google Scholar]
  2. Harrison R.K. Phase II and phase III failures: 2013–2015. Nat. Rev. Drug Discov. 2016 15 12 817 818 10.1038/nrd.2016.184 27811931
    [Google Scholar]
  3. Kongkaew C. Noyce P.R. Ashcroft D.M. Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies. Ann. Pharmacother. 2008 42 7-8 1017 1025 10.1345/aph.1L037 18594048
    [Google Scholar]
  4. Björnsson E.S. Drug-induced liver injury: an overview over the most critical compounds. Arch. Toxicol. 2015 89 3 327 334 10.1007/s00204‑015‑1456‑2 25618544
    [Google Scholar]
  5. Sultana J. Cutroneo P. Trifirò G. Clinical and economic burden of adverse drug reactions. J. Pharmacol. Pharmacother. 2013 4 1_suppl S73 S77 10.4103/0976‑500X.120957 24347988
    [Google Scholar]
  6. Hartung T. Toxicology for the twenty-first century. Nature 2009 460 7252 208 212 10.1038/460208a 19587762
    [Google Scholar]
  7. Kar S. Roy K. QSAR of phytochemicals for the design of better drugs. Expert Opin. Drug Discov. 2012 7 10 877 902 10.1517/17460441.2012.716420 22897485
    [Google Scholar]
  8. Zhang P. Wang F. Hu J. Sorrentino R. Towards personalized medicine: leveraging patient similarity and drug similarity analytics. AMIA Jt. Summits Transl. Sci. Proc. 2014 2014 132 136 25717413
    [Google Scholar]
  9. Topol E.J. High-performance medicine: the convergence of human and artificial intelligence. Nat. Med. 2019 25 1 44 56 10.1038/s41591‑018‑0300‑7 30617339
    [Google Scholar]
  10. Jensen P.B. Jensen L.J. Brunak S. Mining electronic health records: towards better research applications and clinical care. Nat. Rev. Genet. 2012 13 6 395 405 10.1038/nrg3208 22549152
    [Google Scholar]
  11. Liu M. Wu Y. Chen Y. Sun J. Zhao Z. Chen X. Matheny M.E. Xu H. Large-scale prediction of adverse drug reactions using chemical, biological, and phenotypic properties of drugs. J. Am. Med. Inform. Assoc. 2012 19 e1 e28 e35 10.1136/amiajnl‑2011‑000699 22718037
    [Google Scholar]
  12. Bates D.W. Evans R.S. Murff H. Stetson P.D. Pizziferri L. Hripcsak G. Detecting adverse events using information technology. J. Am. Med. Inform. Assoc. 2003 10 2 115 128 10.1197/jamia.M1074 12595401
    [Google Scholar]
  13. Cherkasov A. Muratov E.N. Fourches D. Varnek A. Baskin I.I. Cronin M. Dearden J. Gramatica P. Martin Y.C. Todeschini R. Consonni V. Kuz’min V.E. Cramer R. Benigni R. Yang C. Rathman J. Terfloth L. Gasteiger J. Richard A. Tropsha A. QSAR modeling: where have you been? Where are you going to? J. Med. Chem. 2014 57 12 4977 5010 10.1021/jm4004285 24351051
    [Google Scholar]
  14. Kim J.H. Scialli A.R. Thalidomide: the tragedy of birth defects and the effective treatment of disease. Toxicol. Sci. 2011 122 1 1 6 10.1093/toxsci/kfr088 21507989
    [Google Scholar]
  15. Lenz W. A short history of thalidomide embryopathy. Teratology 1988 38 3 203 215 10.1002/tera.1420380303 3067415
    [Google Scholar]
  16. Kelsey F.O. Thalidomide update: Regulatory aspects. Teratology 1988 38 3 221 226 10.1002/tera.1420380305 3227491
    [Google Scholar]
  17. Krumholz H.M. Ross J.S. Presler A.H. Egilman D.S. What have we learnt from Vioxx? BMJ 2007 334 7585 120 123 10.1136/bmj.39024.487720.68 17235089
    [Google Scholar]
  18. Sibbald B. Rofecoxib (Vioxx) voluntarily withdrawn from market. CMAJ 2004 171 9 1027 1028 10.1503/cmaj.1041606 15505253
    [Google Scholar]
  19. Rockwell M.S. Oyese E.G. Singh E. Vinson M. Yim I. Turner J.K. Epling J.W. A Scoping Review of Interventions to De-implement Potentially Harmful Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Healthcare Settings. medRxiv 2023 10.1101/2023.07.29.23293362
    [Google Scholar]
  20. Hébert P.C. Fergusson D.A. Hutton B. Mazer C.D. Fremes S. Blajchman M. MacAdams C. Wells G. Robblee J. Bussières J. Teoh K. Regulatory decisions pertaining to aprotinin may be putting patients at risk. CMAJ 2014 186 18 1379 1386 10.1503/cmaj.131582 25267766
    [Google Scholar]
  21. Sayuk G.S. Tack J. Tegaserod: what’s old is new again. Clin. Gastroenterol. Hepatol. 2022 20 10 2175 2184.e19 10.1016/j.cgh.2022.01.024 35123085
    [Google Scholar]
  22. Czernichow S. Batty D. Withdrawal of sibutramine for weight loss: where does this leave clinicians? Obes. Facts 2010 3 3 1 10.1159/000316508 20616603
    [Google Scholar]
  23. Chakhtoura M. Haber R. Ghezzawi M. Rhayem C. Tcheroyan R. Mantzoros C.S. Pharmacotherapy of obesity: an update on the available medications and drugs under investigation. EClinicalMedicine 2023 58 101882 10.1016/j.eclinm.2023.101882 36992862
    [Google Scholar]
  24. Reddy S.M. Carroll E. Nanda R. Atezolizumab for the treatment of breast cancer. Expert Rev. Anticancer Ther. 2020 20 3 151 158 10.1080/14737140.2020.1732211 32067545
    [Google Scholar]
  25. Zhang Y. Ma Z. Wang Y. Feng X. An Z. Phosphatidylinositol 3 kinase inhibitor-related pneumonitis: a systematic review and meta-analysis. Expert Rev. Clin. Pharmacol. 2023 16 9 855 863 10.1080/17512433.2023.2238602 37489925
    [Google Scholar]
  26. FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma. 2020 Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma
  27. Reynolds R.F. Lesko S.M. Gatto N.M. van Staa T.P. Mitchell A.A. The Use of Randomized Controlled Trials in Pharmacoepidemiology. Pharmacoepidemiology 2019 792 812 10.1002/9781119413431.ch32
    [Google Scholar]
  28. Obach R.S. Baxter J.G. Liston T.E. Silber B.M. Jones B.C. MacIntyre F. Rance D.J. Wastall P. The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J. Pharmacol. Exp. Ther. 1997 283 1 46 58 9336307
    [Google Scholar]
  29. Zhang Z. Tang W. Drug metabolism in drug discovery and development. Acta Pharm. Sin. B 2018 8 5 721 732 10.1016/j.apsb.2018.04.003 30245961
    [Google Scholar]
  30. Brian Houston J. Carlile D.J. Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices. Drug Metab. Rev. 1997 29 4 891 922 10.3109/03602539709002237 9421679
    [Google Scholar]
  31. Kalvass J.C. Maurer T.S. Pollack G.M. Use of plasma and brain unbound fractions to assess the extent of brain distribution of 34 drugs: comparison of unbound concentration ratios to in vivo p-glycoprotein efflux ratios. Drug Metab. Dispos. 2007 35 4 660 666 10.1124/dmd.106.012294 17237155
    [Google Scholar]
  32. Derendorf H. Schmidt S. Rowland and Tozer's Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications. 2011
    [Google Scholar]
  33. Qiu Y. Chen Y. Zhang G.G. Yu L. Mantri R.V. Developing solid oral dosage forms: Pharmaceutical theory and practice. Academic press 2016
    [Google Scholar]
  34. Collier R. Rapidly rising clinical trial costs worry researchers. CMAJ 2009 180 7 277 8 10.1503/cmaj.082041
    [Google Scholar]
  35. Step 3: Clinical Research. Available from: https://www.fda.gov/patients/drug-development-process/step-3-clinical-research
  36. Huang S.M. Lertora J.J. Vicini P. Atkinson A.J. Jr Atkinson’s principles of clinical pharmacology. Academic Press 2021
    [Google Scholar]
  37. Kaitin K.I. DiMasi J.A. Pharmaceutical innovation in the 21st century: new drug approvals in the first decade, 2000-2009. Clin. Pharmacol. Ther. 2011 89 2 183 188 10.1038/clpt.2010.286 21191382
    [Google Scholar]
  38. Eisenstein E.L. Collins R. Cracknell B.S. Podesta O. Reid E.D. Sandercock P. Shakhov Y. Terrin M.L. Sellers M.A. Califf R.M. Granger C.B. Diaz R. Sensible approaches for reducing clinical trial costs. Clin. Trials 2008 5 1 75 84 10.1177/1740774507087551 18283084
    [Google Scholar]
  39. O’Connell M.B. Korner E.J. Rickles N.M. Sias J.J. Cultural competence in health care and its implications for pharmacy. Part 1. Overview of key concepts in multicultural health care. Pharmacotherapy 2007 27 7 1062 1079 10.1592/phco.27.7.1062 17594213
    [Google Scholar]
  40. Emanuel E.J. Bedarida G. Macci K. Gabler N.B. Rid A. Wendler D. Quantifying the risks of non-oncology phase I research in healthy volunteers: Meta-analysis of phase I studies. BMJ 2015 350 h3271 10.1136/bmj.h3271.
    [Google Scholar]
  41. DiMasi J.A. Feldman L. Seckler A. Wilson A. Trends in risks associated with new drug development: success rates for investigational drugs. Clin. Pharmacol. Ther. 2010 87 3 272 277 10.1038/clpt.2009.295 20130567
    [Google Scholar]
  42. Arrowsmith J. Phase III and submission failures: 2007–2010. Nat. Rev. Drug Discov. 2011 10 2 87 10.1038/nrd3375 21283095
    [Google Scholar]
  43. Giffen C.A. Wagner E.L. Adams J.T. Hitchcock D.M. Welniak L.A. Brennan S.P. Carroll L.E. Providing researchers with online access to NHLBI biospecimen collections: The results of the first six years of the NHLBI BioLINCC program. PLoS One 2017 12 6 e0178141 10.1371/journal.pone.0178141 28614402
    [Google Scholar]
  44. Glickman S.W. McHutchison J.G. Peterson E.D. Cairns C.B. Harrington R.A. Califf R.M. Schulman K.A. Ethical and scientific implications of the globalization of clinical research. N. Engl. J. Med. 2009 360 8 816 823 10.1056/NEJMsb0803929 19228627
    [Google Scholar]
  45. Chan A.W. Tetzlaff J.M. Altman D.G. Laupacis A. Gøtzsche P.C. Krleža-Jerić K. Hróbjartsson A. Mann H. Dickersin K. Berlin J.A. Doré C.J. Parulekar W.R. Summerskill W.S.M. Groves T. Schulz K.F. Sox H.C. Rockhold F.W. Rennie D. Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann. Intern. Med. 2013 158 3 200 207 10.7326/0003‑4819‑158‑3‑201302050‑00583 23295957
    [Google Scholar]
  46. Woodcock J. Woosley R. The FDA critical path initiative and its influence on new drug development. Annu. Rev. Med. 2008 59 1 1 12 10.1146/annurev.med.59.090506.155819 18186700
    [Google Scholar]
  47. Bhatt D.L. Mehta C. Adaptive designs for clinical trials. N. Engl. J. Med. 2016 375 1 65 74 10.1056/NEJMra1510061 27406349
    [Google Scholar]
  48. Sertkaya A. Wong H.H. Jessup A. Beleche T. Key cost drivers of pharmaceutical clinical trials in the United States. Clin. Trials 2016 13 2 117 126 10.1177/1740774515625964 26908540
    [Google Scholar]
  49. Nallamothu B.K. Hayward R.A. Bates E.R. Beyond the randomized clinical trial: the role of effectiveness studies in evaluating cardiovascular therapies. Circulation 2008 118 12 1294 1303 10.1161/CIRCULATIONAHA.107.703579 18794402
    [Google Scholar]
  50. Psaty B.M. Prentice R.L. Minimizing bias in randomized trials: the importance of blinding. JAMA 2010 304 7 793 794 10.1001/jama.2010.1161 20716744
    [Google Scholar]
  51. Shivayogi P. Vulnerable population and methods for their safeguard. Perspect. Clin. Res. 2013 4 1 53 57 10.4103/2229‑3485.106389 23533983
    [Google Scholar]
  52. Smithy J.W. Downing N.S. Ross J.S. Publication of pivotal efficacy trials for novel therapeutic agents approved between 2005 and 2011: a cross-sectional study. JAMA Intern. Med. 2014 174 9 1518 1520 10.1001/jamainternmed.2014.3438 25070357
    [Google Scholar]
  53. Katz M.H. Evaluating clinical and public health interventions: A practical guide to study design and statistics. 2010 10.1017/CBO9780511712074
    [Google Scholar]
  54. Wise J. GSK will resume paying doctors to promote its drugs after policy U turn. BMJ 2018 363 k4157 10.1136/bmj.k4157
    [Google Scholar]
  55. Hempenius M. Drug exposure assessment in pharmacoepidemiological database studies: Reporting and impact of exposure misclassification. Doctoral thesis, Utrecht University
    [Google Scholar]
  56. Davies D.M. Textbook of adverse drug reactions. 1991
    [Google Scholar]
  57. Coleman J.J. Pontefract S.K. Adverse drug reactions. Clin. Med. (Lond.) 2016 16 5 481 485 10.7861/clinmedicine.16‑5‑481 27697815
    [Google Scholar]
  58. Mallal S. Phillips E. Carosi G. Molina J.M. Workman C. Tomažič J. Jägel-Guedes E. Rugina S. Kozyrev O. Cid J.F. Hay P. Nolan D. Hughes S. Hughes A. Ryan S. Fitch N. Thorborn D. Benbow A. HLA-B*5701 screening for hypersensitivity to abacavir. N. Engl. J. Med. 2008 358 6 568 579 10.1056/NEJMoa0706135 18256392
    [Google Scholar]
  59. Aronson J.K. Ferner R.E. Joining the DoTS: new approach to classifying adverse drug reactions. BMJ 2003 327 7425 1222 1225 10.1136/bmj.327.7425.1222 14630763
    [Google Scholar]
  60. Russell S.J. Norvig P. Artificial intelligence a modern approach. Prentice Hall 2010
    [Google Scholar]
  61. Petrovic A. Jovanovic L. Venkatachalam K. Zivkovic M. Bacanin N. Budimirovic N. Anomaly detection in electrocardiogram signals using metaheuristic optimized time-series classification with attention incorporated models. Int. J. Hybrid Intell. Syst. 2024 20 159 183 10.3233/HIS‑240004
    [Google Scholar]
  62. Schneider P. Walters W.P. Plowright A.T. Sieroka N. Listgarten J. Goodnow R.A. Jr Fisher J. Jansen J.M. Duca J.S. Rush T.S. Zentgraf M. Hill J.E. Krutoholow E. Kohler M. Blaney J. Funatsu K. Luebkemann C. Schneider G. Rethinking drug design in the artificial intelligence era. Nat. Rev. Drug Discov. 2020 19 5 353 364 10.1038/s41573‑019‑0050‑3 31801986
    [Google Scholar]
  63. Mohammed M.A. Al-Khateeb B. Yousif M. Mostafa S.A. Kadry S. Abdulkareem K.H. Garcia-Zapirain B. Novel crow swarm optimization algorithm and selection approach for optimal deep learning COVID‐19 diagnostic model. Comput. Intell. Neurosci. 2022 2022 1 1 22 10.1155/2022/1307944 35996653
    [Google Scholar]
  64. Ibrahim R. Ghnemat R. Abu Al-Haija Q. Improving Alzheimer’s Disease and Brain Tumor Detection Using Deep Learning with Particle Swarm Optimization. AI 2023 4 3 551 573 10.3390/ai4030030.
    [Google Scholar]
  65. Lv H. Shi L. Berkenpas J.W. Dao F.Y. Zulfiqar H. Ding H. Zhang Y. Yang L. Cao R. Application of artificial intelligence and machine learning for COVID-19 drug discovery and vaccine design. Brief. Bioinform. 2021 22 6 bbab320 10.1093/bib/bbab320 34410360
    [Google Scholar]
  66. Cai R. Liu M. Hu Y. Melton B.L. Matheny M.E. Xu H. Duan L. Waitman L.R. Identification of adverse drug-drug interactions through causal association rule discovery from spontaneous adverse event reports. Artif Intell Med 2017 76 7 15 10.1016/j.artmed.2017.01.004
    [Google Scholar]
  67. Xiao C. Li Y. Baytas I.M. Zhou J. Wang F. An MCEM framework for drug safety signal detection and combination from heterogeneous real world evidence. Sci. Rep. 2018 8 1 1806 10.1038/s41598‑018‑19979‑7 29379048
    [Google Scholar]
  68. Ren J.J. Sun T. He Y. Zhang Y. A statistical analysis of vaccine-adverse event data. BMC Med. Inform. Decis. Mak. 2019 19 1 101 10.1186/s12911‑019‑0818‑8 31138219
    [Google Scholar]
  69. Li R. Dong Y. Kuang Q. Wu Y. Li Y. Zhu M. Li M. Inductive matrix completion for predicting adverse drug reactions (ADRs) integrating drug–target interactions. Chemom. Intell. Lab. Syst. 2015 144 71 79 10.1016/j.chemolab.2015.03.013
    [Google Scholar]
  70. Zhao J. Henriksson A. Asker L. Boström H. Predictive modeling of structured electronic health records for adverse drug event detection. BMC Med. Inform. Decis. Mak. 2015 15 S4 S1 10.1186/1472‑6947‑15‑S4‑S1 26606038
    [Google Scholar]
  71. Zhao J. Henriksson A. Learning temporal weights of clinical events using variable importance. BMC Med. Inform. Decis. Mak. 2016 16 S2 71 10.1186/s12911‑016‑0311‑6 27459993
    [Google Scholar]
  72. Desautels T. Das R. Calvert J. Trivedi M. Summers C. Wales D.J. Ercole A. Prediction of early unplanned intensive care unit readmission in a UK tertiary care hospital: a cross-sectional machine learning approach. BMJ Open 2017 7 9 e017199 10.1136/bmjopen‑2017‑017199 28918412
    [Google Scholar]
  73. Wang Y. Coiera E. Runciman W. Magrabi F. Using multiclass classification to automate the identification of patient safety incident reports by type and severity. BMC Med. Inform. Decis. Mak. 2017 17 1 84 10.1186/s12911‑017‑0483‑8 28606174
    [Google Scholar]
  74. Wunnava S. Qin X. Kakar T. Sen C. Rundensteiner E.A. Kong X. Adverse drug event detection from electronic health records using hierarchical recurrent neural networks with dual-level embedding. Drug Saf. 2019 42 1 113 122 10.1007/s40264‑018‑0765‑9 30649736
    [Google Scholar]
  75. Harpaz R. DuMouchel W. Shah N.H. Madigan D. Ryan P. Friedman C. Novel data-mining methodologies for adverse drug event discovery and analysis. Clin. Pharmacol. Ther. 2012 91 6 1010 1021 10.1038/clpt.2012.50 22549283
    [Google Scholar]
  76. Ai H. Chen W. Zhang L. Huang L. Yin Z. Hu H. Zhao Q. Zhao J. Liu H. Predicting drug-induced liver injury using ensemble learning methods and molecular fingerprints. Toxicol. Sci. 2018 165 1 100 107 10.1093/toxsci/kfy121 29788510
    [Google Scholar]
  77. Whitebread S. Hamon J. Bojanic D. Urban L. Keynote review: In vitro safety pharmacology profiling: an essential tool for successful drug development. Drug Discov. Today 2005 10 21 1421 1433 10.1016/S1359‑6446(05)03632‑9 16243262
    [Google Scholar]
  78. Ekins S. Williams A.J. Krasowski M.D. Freundlich J.S. In silico repositioning of approved drugs for rare and neglected diseases. Drug Discov. Today 2011 16 7-8 298 310 10.1016/j.drudis.2011.02.016 21376136
    [Google Scholar]
  79. Jovanovic L. Damaševičius R. Matic R. Kabiljo M. Simic V. Kunjadic G. Antonijevic M. Zivkovic M. Bacanin N. Detecting Parkinson’s disease from shoe-mounted accelerometer sensors using convolutional neural networks optimized with modified metaheuristics. PeerJ Comput. Sci. 2024 10 e2031 10.7717/peerj‑cs.2031 38855236
    [Google Scholar]
  80. Gao M. Igata H. Takeuchi A. Sato K. Ikegaya Y. Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds. J. Pharmacol. Sci. 2017 133 2 70 78 10.1016/j.jphs.2017.01.003 28215473
    [Google Scholar]
  81. Hughes T.B. Miller G.P. Swamidass S.J. Site of reactivity models predict molecular reactivity of diverse chemicals with glutathione. Chem. Res. Toxicol. 2015 28 4 797 809 10.1021/acs.chemrestox.5b00017 25742281
    [Google Scholar]
  82. Roy K. Kar S. Das R.N. Understanding the basics of QSAR for applications in pharmaceutical sciences and risk assessment. Academic Press 2015
    [Google Scholar]
  83. Kar S. Leszczynski J. Exploration of Computational Approaches to Predict the Toxicity of Chemical Mixtures. Toxics 2019 7 1 15 10.3390/toxics7010015 30893892
    [Google Scholar]
  84. Roy K. Kar S. Ambure P. On a simple approach for determining applicability domain of QSAR models. Chemom. Intell. Lab. Syst. 2015 145 22 29 10.1016/j.chemolab.2015.04.013
    [Google Scholar]
  85. Roy K. Kar S. A primer on QSAR/QSPR modeling: Fundamental concepts. Springer 2015 10.1007/978‑3‑319‑17281‑1.
    [Google Scholar]
  86. Puzyn T. Gajewicz A. Leszczynska D. Leszczynski J. Nanomaterials–the next great challenge for QSAR modelers. Recent Advances in QSAR Studies 2010 383 409 10.1007/978‑1‑4020‑9783‑6_14
    [Google Scholar]
  87. Liu J. Mansouri K. Judson R.S. Martin M.T. Hong H. Chen M. Xu X. Thomas R.S. Shah I. Predicting hepatotoxicity using ToxCast in vitro bioactivity and chemical structure. Chem. Res. Toxicol. 2015 28 4 738 751 10.1021/tx500501h 25697799
    [Google Scholar]
  88. Wang T. Wu M.B. Lin J.P. Yang L.R. Quantitative structure–activity relationship: promising advances in drug discovery platforms. Expert Opin. Drug Discov. 2015 10 12 1283 1300 10.1517/17460441.2015.1083006 26358617
    [Google Scholar]
  89. Mamoshina P. Vieira A. Putin E. Zhavoronkov A. Applications of deep learning in biomedicine. Mol. Pharm. 2016 13 5 1445 1454 10.1021/acs.molpharmaceut.5b00982 27007977
    [Google Scholar]
  90. Rajkomar A. Dean J. Kohane I. Machine learning in medicine. N. Engl. J. Med. 2019 380 14 1347 1358 10.1056/NEJMra1814259 30943338
    [Google Scholar]
  91. Zeng X. Zhu S. Liu X. Zhou Y. Nussinov R. Cheng F. deepDR: a network-based deep learning approach to in silico drug repositioning. Bioinformatics 2019 35 24 5191 5198 10.1093/bioinformatics/btz418 31116390
    [Google Scholar]
  92. Yu K.H. Kohane I.S. Framing the challenges of artificial intelligence in medicine. BMJ Qual. Saf. 2018 30291179
    [Google Scholar]
  93. Edwards I.R. Aronson J.K. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000 356 9237 1255 1259 10.1016/S0140‑6736(00)02799‑9 11072960
    [Google Scholar]
  94. Banda J.M. Evans L. Vanguri R.S. Tatonetti N.P. Ryan P.B. Shah N.H. A curated and standardized adverse drug event resource to accelerate drug safety research. Sci. Data 2016 3 1 160026 10.1038/sdata.2016.26 27193236
    [Google Scholar]
  95. Karimi S. Wang C. Metke-Jimenez A. Gaire R. Paris C. Text and data mining techniques in adverse drug reaction detection. ACM Comput. Surv. 2015 47 4 1 39 10.1145/2719920
    [Google Scholar]
  96. Harpaz R. DuMouchel W. LePendu P. Bauer-Mehren A. Ryan P. Shah N.H. Performance of pharmacovigilance signal-detection algorithms for the FDA adverse event reporting system. Clin. Pharmacol. Ther. 2013 93 6 539 546 10.1038/clpt.2013.24 23571771
    [Google Scholar]
  97. Bajorath J. Integration of virtual and high-throughput screening. Nat. Rev. Drug Discov. 2002 1 11 882 894 10.1038/nrd941 12415248
    [Google Scholar]
  98. Merk D. Friedrich L. Grisoni F. Schneider G. De novo design of bioactive small molecules by artificial intelligence. Mol. Inform. 2018 37 1-2 1700153 10.1002/minf.201700153 29319225
    [Google Scholar]
  99. Zhavoronkov A. Ivanenkov Y.A. Aliper A. Veselov M.S. Aladinskiy V.A. Aladinskaya A.V. Terentiev V.A. Polykovskiy D.A. Kuznetsov M.D. Asadulaev A. Volkov Y. Zholus A. Shayakhmetov R.R. Zhebrak A. Minaeva L.I. Zagribelnyy B.A. Lee L.H. Soll R. Madge D. Xing L. Guo T. Aspuru-Guzik A. Deep learning enables rapid identification of potent DDR1 kinase inhibitors. Nat. Biotechnol. 2019 37 9 1038 1040 10.1038/s41587‑019‑0224‑x 31477924
    [Google Scholar]
  100. Pushpakom S. Iorio F. Eyers P.A. Escott K.J. Hopper S. Wells A. Doig A. Guilliams T. Latimer J. McNamee C. Norris A. Sanseau P. Cavalla D. Pirmohamed M. Drug repurposing: progress, challenges and recommendations. Nat. Rev. Drug Discov. 2019 18 1 41 58 10.1038/nrd.2018.168 30310233
    [Google Scholar]
  101. Pérez Santín E. Rodríguez Solana R. González García M. García Suárez M.D.M. Blanco Díaz G.D. Cima Cabal M.D. Moreno Rojas J.M. López Sánchez J.I. Toxicity prediction based on artificial intelligence: A multidisciplinary overview. Wiley Interdiscip. Rev. Comput. Mol. Sci. 2021 11 5 e1516 10.1002/wcms.1516
    [Google Scholar]
  102. Singh A.V. Rosenkranz D. Ansari M.H.D. Singh R. Kanase A. Singh S.P. Johnston B. Tentschert J. Laux P. Luch A. Artificial intelligence and machine learning empower advanced biomedical material design to toxicity prediction. Adv. Intell. Syst. 2020 2 12 2000084 10.1002/aisy.202000084
    [Google Scholar]
  103. Basile A.O. Yahi A. Tatonetti N.P. Artificial intelligence for drug toxicity and safety. Trends Pharmacol. Sci. 2019 40 9 624 635 10.1016/j.tips.2019.07.005 31383376
    [Google Scholar]
  104. Jaganathan K. Tayara H. Chong K.T. Prediction of drug-induced liver toxicity using SVM and optimal descriptor sets. Int. J. Mol. Sci. 2021 22 15 8073 10.3390/ijms22158073 34360838
    [Google Scholar]
  105. Rao M. Nassiri V. Alhambra C. Snoeys J. Van Goethem F. Irrechukwu O. Aleo M.D. Geys H. Mitra K. Will Y. AI/ML Models to Predict the Severity of Drug-Induced Liver Injury for Small Molecules. Chem. Res. Toxicol. 2023 36 7 1129 1139 10.1021/acs.chemrestox.3c00098 37294641
    [Google Scholar]
  106. Kandasamy K. Chuah J.K.C. Su R. Huang P. Eng K.G. Xiong S. Li Y. Chia C.S. Loo L.H. Zink D. Prediction of drug-induced nephrotoxicity and injury mechanisms with human induced pluripotent stem cell-derived cells and machine learning methods. Sci. Rep. 2015 5 1 12337 10.1038/srep12337 26212763
    [Google Scholar]
  107. Cheng P. Waitman L.R. Hu Y. Liu M. Predicting Inpatient Acute Kidney Injury over Different Time Horizons: How Early and Accurate? AMIA Annu Symp Proc 2018 2017 565 574 29854121
    [Google Scholar]
  108. Kar S. Roy K. Prediction of hERG potassium channel blocking actions using combination of classification and regression based models: a mixed descriptors approach. Mol. Inform. 2012 31 11-12 879 894 10.1002/minf.201200039 27476741
    [Google Scholar]
  109. Cai C. Guo P. Zhou Y. Zhou J. Wang Q. Zhang F. Fang J. Cheng F. Deep learning-based prediction of drug-induced cardiotoxicity. J. Chem. Inf. Model. 2019 59 3 1073 1084 10.1021/acs.jcim.8b00769 30715873
    [Google Scholar]
  110. Zhao X. Sun Y. Zhang R. Chen Z. Hua Y. Zhang P. Guo H. Cui X. Huang X. Li X. Machine Learning Modeling and Insights into the Structural Characteristics of Drug-Induced Neurotoxicity. J. Chem. Inf. Model. 2022 62 23 6035 6045 10.1021/acs.jcim.2c01131 36448818
    [Google Scholar]
  111. Jiang C. Zhao P. Li W. Tang Y. Liu G. In silico prediction of chemical neurotoxicity using machine learning. Toxicol. Res. (Camb.) 2020 9 3 164 172 10.1093/toxres/tfaa016 32670548
    [Google Scholar]
  112. Kar S. Roy K. Development and validation of a robust QSAR model for prediction of carcinogenicity of drugs. Indian J Biochem Biophys. 2011 48 2 111 22 21682143
    [Google Scholar]
  113. Li T. Tong W. Roberts R. Liu Z. Thakkar S. DeepCarc: Deep Learning-Powered Carcinogenicity Prediction Using Model-Level Representation. Front Artif Intell 2021 4 757780 10.3389/frai.2021.757780.
    [Google Scholar]
  114. Nandy A. Kar S. Roy K. Development and validation of regression-based QSAR models for quantification of contributions of molecular fragments to skin sensitization potency of diverse organic chemicals. SAR QSAR Environ. Res. 2013 24 12 1009 1023 10.1080/1062936X.2013.821422 23988224
    [Google Scholar]
  115. Nandy A. Kar S. Roy K. Linear discriminant analysis for skin sensitisation potential of diverse organic chemicals. Mol. Simul. 2013 39 6 432 441 10.1080/08927022.2012.738421
    [Google Scholar]
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