Добавил:
kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз: Предмет: Файл:

Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_117_библиотеки_им_акад_М_И_Перельмана

.pdf
Скачиваний:
2
Добавлен:
15.09.2026
Размер:
15 Мб
Скачать
☆
126
A. V. Geevarghese
generation have gently grown in acceptance. Although both of them show potential in probing newly uncharted molecular time, but additionally come with disadvan­tages, like limited ability to be synthesised. “Hybrid” techniques, which mix rule­free and rules-based techniques, could be an acceptable substitute. A special emphasis is going to be given to generative techniques that may take advantage of additional sources of data, including a few of the groundbreaking research on the expression of genes, conformation space and the understanding of ligand binding locations. Advanced machine learning for natural language processing is going to continue to serve as a source of inspiration and an engine of innovation for auto­mated synthesising scheduling and response predictions. Frequently under­examined topics including yield estimation, side-product generation after generation, and forecasting of favourable reaction situations will receive vital attention. In the years to come, advances in robots and learning by reinforcement will lay a basis for entirely automated synthesis. The acceptance of articial intelligence-supported discovery of drugs will increase due to the comeback in interest in explainable AI and methods like feature attribute, instance-based molecular hypothetical justica­tion, and uncertainty prediction. Further research across disciplines will be required for the development and verication for these methodologies. A special focus will also be placed on techniques which could make use of information in low-data regimes, including transferable learning, juggling multiple tasks and meta-learning, or for motivated professionals, the barriers to acquiring and applying advanced learning methods have been substantially reduced in the past few years. Given an ongoing creation of broad a high-level studies and installation programmes, and also comprehensive documentation, the current state of affairs implies that these techniques will grow easier to obtain in the not-too-distant future. Using methods including feature identication, instance-based molecule causal explanation, and unpredictability, explicable articial intelligence is currently gaining prominence. According to an assessment, it will increase the market of AI-assisted discovery of drugs. Further research across disciplines is going to be needed for the development and verication of such strategies. In addition, techniques that may make advantage of data in low-data regimes, like as transfer learning, juggling multiple tasks and the concept of meta-, will get special emphasis. The obstacles to studying and using advanced learning approaches have signicantly decreased for dedicated profes­sionals in recent years. The present trend indicates that these approaches will soon become more widely available given the continuing development of numerous high­level research and installation projects with understandable records.
References
1. Vamathevan J, Clark D, Czodrowski P etal (2019) Applications of machine learning in drug discovery and development. Nat Rev Drug Discov 18(6):463–477
2. Lavecchia A (2015) Machine-learning approaches in drug discovery: methods and applica­tions. Drug Discov Today 20(3):318–331
Explainable Articial Intelligence inDrug Discovery
3. Lo Y-C, Rensi SE, Torng W etal (2018) Machine learning in chemoinformatics and drug discovery. Drug Discov Today 23(8):1538–1546
4. Xue L, Bajorath J (2000) Molecular descriptors in chemoinformatics, computational combi­natorial chemistry, and virtual screening. Comb Chem High Throughput Screen 3(5):363–372
5. Todeschini R, Consonni V (2009) Molecular descriptors for chemoinformatics: volume I: alphabetical listing/volume II: appendices, references. Wiley, Weinheim
6. Schneider G (2019) Mind and machine in drug design. Nat Mach Intell 1(3):128–130
7. Wu Z, Ramsundar B, Feinberg E etal (2018) MoleculeNet: a benchmark for molecular machine learning. Chem Sci 9(2):513–530
8. Feinberg EN, Sur D, Wu Z etal (2018) PotentialNet for molecular property prediction. ACS Cent Sci 4(11):1520–1530
9. Kearnes S, McCloskey K, Berndl M etal (2016) Molecular graph convolutions: moving beyond ngerprints. J Comput Aided Mol Des 30(8):595–608
10. Gilmer J, Schoenholz SS, Riley PF etal (2017) Neural message passing for quantum chem­istry. arXiv [cs.LG]
11. Gawehn E, Hiss JA, Schneider G (2016) Deep learning in drug discovery. Mol Inform 35(1):3–14
12. Zhang L, Tan J, Han D etal (2017) From machine learning to deep learning: progress in machine intelligence for rational drug discovery. Drug Discov Today 22(11):1680–1685
13. Chen H, Engkvist O, Wang Y etal (2018) The rise of deep learning in drug discovery. Drug Discov Today 23(6):1241–1250
14. Muratov EN etal (2020) QSAR without borders. Chem Soc Rev 49:3525–3564
15. Lenselink EB etal (2017) Beyond the hype: deep neural networks outperform established methods using a ChEMBL bioactivity benchmark set. J Cheminform 9:45
16. Goh GB, Siegel C, Vishnu A, Hodas NO, Baker N (2017) Chemception: a deep neural net­work with minimal chemistry knowledge matches the performance of expert-developed QSAR/QSPR models. Preprint at https://arxiv.org/abs/1706.06689
17. Unterthiner T etal (2014) Deep learning as an opportunity in virtual screening. In: Proc. deep learning workshop at NIPS 27. NIPS, pp1–9
18. Schwaller P, Gaudin T, Lanyi D, Bekas C, Laino T (2018) ‘Found in translation’: predicting outcomes of complex organic chemistry reactions using neural sequence-to-sequence mod­els. Chem Sci 9:6091–6098
19. Coley CW, Green WH, Jensen KF (2018) Machine learning in computer-aided synthesis planning. Acc Chem Res 51:1281–1289
20. Öztürk H, Özgür A, Ozkirimli E (2018) DeepDTA: deep drug–target binding afnity predic­tion. Bioinformatics 34:i821–i829
21. Jimenez J etal (2018) Pathwaymap: molecular pathway association with self-normalizing neural networks. J Chem Inf Model 59:1172–1181
22. Marchese Robinson RL, Palczewska A, Palczewski J, Kidley N (2017) Comparison of the predictive performance and interpretability of random forest and linear models on benchmark data sets. J Chem Inf Model 57:1773–1792
23. Webb SJ, Hanser T, Howlin B, Krause P, Vessey JD (2014) Feature combination networks for the interpretation of statistical machine learning models: application to Ames mutagenicity. J Cheminform 6:8
24. Grisoni F, Consonni V, Ballabio D (2019) Machine learning consensus to predict the binding to the androgen receptor within the CoMPARA project. J Chem Inf Model 59:1839–1848
25. Chen Y, Stork C, Hirte S, Kirchmair J (2019) NP-scout: machine learning approach for the quantication and visualization of the natural product-likeness of small molecules. Biomol Ther 9:43
26. Riniker S, Landrum GA (2013) Similarity maps—a visualization strategy for molecular n­gerprints and machine-learning methods. J Cheminform 5:43
27. Marcou G etal (2012) Interpretability of sar/qsar models of any complexity by atomic con­tributions. Mol Inform 31:639–642
127
128
28. Rudin C (2019) Stop explaining black box machine learning models for high stakes decisions and use interpretable models instead. Nat Mach Intell 1:206–215
29. Gupta M, Lee HJ, Barden CJ, Weaver DF (2019) The blood–brain barrier (BBB) score. J Med Chem 62:9824–9836
30. Rankovic Z (2017) CNS physicochemical property space shaped by a diverse set of mol­ecules with experimentally determined exposure in the mouse brain: miniperspective. J Med Chem 60:5943–5954
31. Leeson PD, Young RJ (2015) Molecular property design: does everyone get it? ACS Med Chem Lett 6:722–725
32. Hirst JD, King RD, Sternberg MJ (1994) Quantitative structure–activity relationships by neu­ral networks and inductive logic programming. I.The inhibition of dihydrofolate reductase by pyrimidines. J Comput Aided Mol Des 8:405–420
33. Fiore M, Sicurello F, Indorato G (1995) An integrated system to represent and manage medi­cal knowledge. Medinfo 8:931–933
34. Goebel R etal (2018) Explainable AI: the new 42? In: Holzinger A, Kieseberg P, Tjoa A, Weippl E (eds) Machine learning and knowledge extraction. CD-MAKE 2018. Lecture notes in computer science, vol 11015. Springer, Cham
35. Doshi-Velez F, Kim B (2017) Towards a rigorous science of interpretable machine learning. Preprint at https://arxiv.org/abs/1702.08608
36. Lapuschkin S etal (2019) Unmasking clever Hans predictors and assessing what machines really learn. Nat Commun 10:1096
37. Miller T (2019) Explanation in articial intelligence: insights from the social sciences. Artif Intell 267:1–38
38. Chander A, Srinivasan R, Chelian S, Wang J, Uchino K (2018) Working with beliefs: AI transparency in the enterprise. In: Said A, Komatsu T (eds) Joint Proceedings of the ACM IUI 2018 workshops co-located with the 23rd ACM conference on intelligent user interfaces
2068. CEUR-WS.org
39. Guidotti R etal (2018) A survey of methods for explaining black box models. ACM Comput Surv 51:93
40. Lundberg SM etal (2020) From local explanations to global understanding with explainable AI for trees. Nat Mach Intell 2:2522–5839
41. Bendassolli PF (2013) Theory building in qualitative research: reconsidering the problem of induction. Forum Qual Soc Res 14:20
42. Schneider P, Schneider G (2016) De novo design at the edge of chaos: miniperspective. J Med Chem 59:4077–4086
43. Liao QV, Gruen D, Miller S (2020) Questioning the AI: informing design practices for explainable AI user experiences. In: Proc. 2020 CHI conference on human factors in comput­ing systems, CHI ’20. ACM, pp1–15
44. Sheridan RP (2019) Interpretation of QSAR models by coloring atoms according to changes in predicted activity: how robust is it? J Chem Inf Model 59:1324–1337
45. Preuer K, Klambauer G, Rippmann F, Hochreiter S, Unterthiner T (2019) In: Samek W etal (eds) Interpretable deep learning in drug discovery. Springer, pp331–345
46. Xu Y, Pei J, Lai L (2017) Deep learning based regression and multiclass models for acute oral toxicity prediction with automatic chemical feature extraction. J Chem Inf Model 57:2672–2685
47. Ciallella HL, Zhu H (2019) Advancing computational toxicology in the big data era by arti­cial intelligence: data-driven and mechanism-driven modeling for chemical toxicity. Chem Res Toxicol 32:536–547
48. Dey S, Luo H, Fokoue A, Hu J, Zhang P (2018) Predicting adverse drug reactions through interpretable deep learning framework. BMC Bioinform 19:476
49. Kutchukian PS etal (2012) Inside the mind of a medicinal chemist: the role of human bias in compound prioritization during drug discovery. PLoS One 7:e48476
A. V. Geevarghese
Explainable Articial Intelligence inDrug Discovery
50. Boobier S, Osbourn A, Mitchell JB (2017) Can human experts predict solubility better than computers? J Cheminform 9:63
51. Hansch C, Maloney PP, Fujita T et al (1962) Correlation of biological activity of phen­oxyacetic acids with Hammett substituent constants and partition coefcients. Nature 194(4824):178–180
52. Goller A, Kuhnke L, Montanari F etal (2020) Bayer’s in silico ADMET platform: a journey of machine learning over the past two decades. Drug Discov Today 25(9):1702–1709
53. Winiwarter S, Ahlberg E, Watson E etal (2018) In silico ADME in drug design—enhancing the impact. ADMET DMPK 6(1):15–33
54. Beresford AP, Segall M, Tarbit MH (2004) In silico prediction of ADME properties: are we making progress? Curr Opin Drug Discov Devel 7(1):36–42
55. Norinder U, Bergstrom CAS (2006) Prediction of ADMET properties. ChemMedChem 1(9):920–937
56. Beck B, Geppert T (2014) Industrial applications of in silico ADMET. J Mol Model 20(7):2322. https://doi.org/10.1007/s00894- 014- 2322- 5
57. Fujita T, Winkler DA (2016) Understanding the roles of the ‘two QSARs. J Chem Inf Model 56(2):269–274
58. Rumelhart DE, McClelland JL (1986) Parallel distributed processing: explorations in the microstructure of cognition, vol 1: foundations. MIT Press, Cambridge, MA
59. Zupan J, Gasteiger J (1993) Neural networks for chemists: an introduction. Wiley, NewYork
60. Devillers J (1996) Neural networks in QSAR and drug design. Academic Press, Lyon
61. Schneider G (2002) Adaptive systems in drug design. CRC Press, Boca Raton, FL
62. Unterthiner T, Mayr A, Klambauer G etal (2014) Deep learning as an opportunity in virtual screening. In: Proceedings of the deep learning workshop at NIPS, Montreal, Canada, vol 27, pp1–9
63. Sheridan RP, Wang WM, Liaw A etal (2016) Extreme gradient boosting as a method for quantitative structure–activity relationships. J Chem Inf Model 56(12):2353–2360
64. Winkler DA, Le TC (2017) Performance of deep and shallow neural networks, the universal approximation theorem, activity cliffs, and QSAR.Mol Inform 36(1–2):1600118
65. Henninot A, Collins JC, Nuss JM (2018) The current state of peptide drug discovery: back to the future? J Med Chem 61(4):1382–1414
66. Chakravarti SK, Alla SRM (2019) Descriptor-free QSAR modeling using deep learning with long short-term memory neural networks. Front Artif Intell Appl 2:17
67. Zou Y, Ma D, The WY (2019) PROTAC technology in drug development. Cell Biochem Funct 37(1):21–30
68. Ramsundar B, Kearnes S, Riley P etal (2015) Massively multitask networks for drug discov­ery. arXiv [stat.ML]
69. Simoes RS, Maltarollo VG, Oliveira PR et al (2018) Transfer and multi-task learning in QSAR modeling: advances and challenges. Front Pharmacol 9:74. https://doi.org/10.3389/
fphar.2018.00074
70. Sosnin S, Karlov D, Tetko IV etal (2019) Comparative study of multitask toxicity modeling on a broad chemical space. J Chem Inf Model 59(3):1062–1072
71. Vilar S, Santana L, Uriarte E (2006) Probabilistic neural network model for the in silico evaluation of anti-HIV activity and mechanism of action. J Med Chem 49(3):1118–1124
72. Prado-Prado FJ, Garcia-Mera X, Gonzalez-Diaz H (2010) Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species. Bioorg Med Chem 18(6):2225–2231
73. Speck-Planche A, Kleandrova VV, Luan F etal (2012) Rational drug design for anti-cancer chemotherapy: multi-target QSAR models for the in silico discovery of anti-colorectal cancer agents. Bioorg Med Chem 20(15):4848–4855
74. Speck-Planche A, Kleandrova VV, Cordeiro MNDS (2013) Chemoinformatics for ratio­nal discovery of safe antibacterial drugs: simultaneous predictions of biological activity
129
130
against streptococci and toxicological proles in laboratory animals. Bioorg Med Chem 21(10):2727–2732
75. Speck-Planche A, Cordeiro MNDS (2015) Multitasking models for quantitative structure– biological effect relationships: current status and future perspectives to speed up drug discov­ery. Expert Opin Drug Discov 10(3):245–256
76. Ambure P, Halder AK, Gonzalez Diaz H etal (2019) QSAR-Co: an open source software for developing robust multitasking or multitarget classication-based QSAR models. J Chem Inf Model 59(6):2538–2544
77. Montanari F, Kuhnke L, Ter Laak A etal (2019) Modeling physico-chemical ADMET end­points with multitask graph convolutional networks. Molecules 25(1):44
78. Wenzel J, Matter H, Schmidt F (2019) Predictive multitask deep neural network models for ADME-Tox properties: learning from large data sets. J Chem Inf Model 59(3):1253–1268
79. Rodriguez-Perez R, Bajorath J (2018) Prediction of compound proling matrices, part II: relative performance of multitask deep learning and random forest classication on the basis of varying amounts of training data. ACS Omega 3(9):12033–12040
80. Merget B, Turk S, Eid S etal (2017) Proling prediction of kinase inhibitors: toward the virtual assay. J Med Chem 60(1):474–485
81. Lenselink EB, Ten Dijke N, Bongers B etal (2017) Beyond the hype: deep neural networks outperform established methods using a ChEMBL bioactivity benchmark set. J Cheminform 9:45. https://doi.org/10.1186/s13321- 017- 0232- 0
82. Chu Y, Kaushik AM, Wang X et al (2021) DTI-CDF: a cascade deep forest model towards the prediction of drug-target interactions based on hybrid features. Brief Bioinform 22(1):451–462
83. Altae-Tran H, Ramsundar B, Pappu AS etal (2017) Low data drug discovery with one-shot learning. ACS Cent Sci 3(4):283–293
84. Finn C, Abbeel P, Levine S (2017) Model-agnostic meta-learning for fast adaptation of deep networks. arXiv [cs.LG]
85. Reker D, Schneider G (2015) Active-learning strategies in computer-assisted drug discovery. Drug Discov Today 20(4):458–465
86. Wachter S, Mittelstadt B, Russell C (2017) Counterfactual explanations without opening the black box: automated decisions and the GDPR.Harv JL Tech 31:841–887
87. Mauri A (2020) alvaDesc: a tool to calculate and analyze molecular descriptors and nger­prints. In: Roy K (ed) Ecotoxicological QSARs. Springer, NewYork, pp801–820
88. Moriwaki H, Tian Y-S, Kawashita N et al (2018) A molecular descriptor calculator. J Cheminform 10:4. https://doi.org/10.1186/s13321- 018- 0258- y
89. Jimenez-Luna J, Grisoni F, Schneider G (2020) Drug discovery with explainable articial intelligence. Nat Mach Intell 2(10):573–584
90. Sundararajan M, Taly A, Yan Q (2017) Axiomatic attribution for deep networks. arXiv [cs.LG]
91. Preuer K, Klambauer G, Rippmann F etal (2019) Interpretable deep learning in drug discov­ery. In: Samek W, Montavon G, Vedaldi A etal (eds) Explainable AI: interpreting, explaining and visualizing deep learning. Springer, Cham, pp331–345
92. Gawehn E, Hiss JA, Brown JB etal (2018) Advancing drug discovery via GPU-based deep learning. Expert Opin Drug Discov 13(7):579–582
93. Lapuschkin S, Waldchen S, Binder A etal (2019) Unmasking Clever Hans predictors and assessing what machines really learn. Nat Commun 10(1):1096
94. Nguyen A, Yosinski J, Clune J (2015) Deep neural networks are easily fooled: high con­dence predictions for unrecognizable images. In: Proceedings of the IEEE conference on computer vision and pattern recognition, Boston, MA, pp427–436
95. Graves A (2011) Practical variational inference for neural networks. In: Shawe-Taylor J, Zemel RS, Bartlett PL etal (eds) Adv. neural inf. process. syst. 24. Curran Associates, Inc., Granada, pp2348–2356
A. V. Geevarghese
Explainable Articial Intelligence inDrug Discovery
96. Lakshminarayanan B, Pritzel A, Blundell C etal (2017) Simple and scalable predictive uncer­tainty estimation using deep ensembles. In: Guyon I (ed) Adv. neural inf. process. syst. 30. Curran Associates, Inc., Long Beach, CA, pp6402–6413
97. Cao Y, Li L (2014) Improved protein–ligand binding afnity prediction by using a curvature­dependent surface-area model. Bioinformatics 30(12):1674–1680
98. Wang R, Lai L, Wang S (2002) Further development and validation of empirical scoring func­tions for structure-based binding afnity prediction. J Comput Aided Mol Des 16(1):11–26
99. Bohm HJ (1998) Prediction of binding constants of protein ligands: a fast method for the prioritization of hits obtained from de novo design or 3D database search programs. J Comput Aided Mol Des 12(4):309–323
100. Wang R, Liu L, Lai L etal (1998) SCORE: a new empirical method for estimating the bind­ing afnity of a protein-ligand complex. Mol Mod Annu 4(12):379–394
101. Ain QU, Aleksandrova A, Roessler FD etal (2015) Machine-learning scoring functions to improve structure-based binding afnity prediction and virtual screening. Wiley Interdiscip Rev Comput Mol Sci 5(6):405–424
102. Ballester PJ, Mitchell JBO (2010) A machine learning approach to predicting protein–ligand binding afnity with applications to molecular docking. Bioinformatics 26(9):1169–1175
103. Pereira JC, Caffarena ER, dos Santos CN (2016) Boosting docking-based virtual screening with deep learning. J Chem Inf Model 56(12):2495–2506
104. Ragoza M, Hochuli J, Idrobo E etal (2017) Protein–ligand scoring with convolutional neural networks. J Chem Inf Model 57(4):942–957
105. Jimenez J, Škalič M, Martinez-Rosell G etal (2018) K DEEP: protein–ligand absolute binding afnity prediction via 3D-convolutional neural networks. J Chem Inf Model 58(2):287–296
106. Hochuli J, Helbling A, Skaist T etal (2018) Visualizing convolutional neural network protein­ligand scoring. J Mol Graph Model 84:96–108
107. Skalic M, Martinez-Rosell G, Jimenez J etal (2019) PlayMolecule BindScope: large scale CNN-based virtual screening on the web. Bioinformatics 35:1237–1238
108. Sunseri J, King JE, Francoeur PG etal (2019) Convolutional neural network scoring and minimization in the D3R 2017 community challenge. J Comput Aided Mol Des 33(1):19–34
109. Li H, Sze K, Lu G etal (2021) Machine-learning scoring functions for structure-based vir­tual screening. Wiley Interdiscip Rev Comput Mol Sci 11(1):e1478. https://doi.org/10.1002/
wcms.1478
110. Sieg J, Flachsenberg F, Rarey M (2019) In need of bias control: evaluating chemical data for machine learning in structure-based virtual screening. J Chem Inf Model 59(3):947–961
111. Thomas N, Smidt T, Kearnes S etal (2018) Tensor eld networks: rotation-and translation­equivariant neural networks for 3d point clouds. arXiv preprint arXiv
112. Cohen TS, Geiger M, Kohler J etal (2018) Spherical CNNs. arXiv preprint arXiv
113. Anderson B, Hy TS, Kondor R (2019) Cormorant: covariant molecular neural networks. Adv Neural Inf Process Syst 32:14537–14546
114. Schutt KT, Sauceda HE, Kindermans PJ etal (2018) SchNet–a deep learning architecture for molecules and materials. J Chem Phys 148:241722
115. Qiao Z, Welborn M, Anandkumar A etal (2020) OrbNet: deep learning for quantum chemis­try using symmetry-adapted atomic-orbital features. J Chem Phys 153(124111):124111
116. Irwin JJ, Shoichet BK (2005) ZINC—a free database of commercially available compounds for virtual screening. J Chem Inf Model 45:177–182
117. Gaulton A, Hersey A, Nowotka M etal (2017) The ChEMBL database in 2017. Nucleic Acids Res 45(D1):D945–D954
118. Liu Z, Li Y, Han L etal (2015) PDB-wide collection of binding data: current status of the PDBbind database. Bioinformatics 31(3):405–412
119. Liu T, Lin Y, Wen X etal (2006) BindingDB: a web-accessible database of experimentally determined protein–ligand binding afnities. Nucleic Acids Res 35(Database):D198–D201
120. Senior AW, Evans R, Jumper J etal (2020) Improved protein structure prediction using poten­tials from deep learning. Nature 577(7792):706–710
131
132
121. Si D, Moritz SA, Pfab J etal (2020) Deep learning to predict protein backbone structure from high-resolution cryo-EM density maps. Sci Rep 10:4282. https://doi.org/10.1038/
s41598- 020- 60598- y
122. Wassermann AM, Lounkine E, Hoepfner D etal (2015) Dark chemical matter as a promising starting point for drug lead discovery. Nat Chem Biol 11:958–966
123. Engels MFM, Gibbs AC, Jaeger EP etal (2006) A cluster-based strategy for assessing the overlap between large chemical libraries and its application to a recent acquisition. J Chem Inf Model 46(6):2651–2660
124. Kogej T, Blomberg N, Greasly PJ et al (2013) Big pharma screening collections: more of the same or unique libraries? The AstraZeneca-Bayer Pharma AG case. Drug Discov Today 18(19–20):1014–1024
125. Le T, Winter R, Noe F et al (2020) Neuraldecipher—reverse-engineering extended­connectivity ngerprints (ECFPs) to their molecular structures. Chem Sci 11(38):10378–10389
126. Sheridan RP (2013) Time-split cross-validation as a method for estimating the goodness of prospective prediction. J Chem Inf Model 53(4):783–790
127. Ortwine DF, Aliagas I (2013) Physicochemical and DMPK in silico models: facilitating their use by medicinal chemists. Mol Pharm 10(4):1153–1161
128. Ballester PJ (2019) Selecting machine-learning scoring functions for structure-based virtual screening. Drug Discov Today Technol 32-33:81–87
129. Durrant JD, Carlson KE, Martin TE etal (2015) Neural-network scoring functions identify structurally novel estrogen-receptor ligands. J Chem Inf Model 55(9):1953–1961
130. Alexander DLJ, Tropsha A, Winkler DA (2015) Beware of R2: simple, unambiguous assessment of the prediction accuracy of QSAR and QSPR models. J Chem Inf Model 55(7):1316–1322
131. Todeschini R, Ballabio D, Grisoni F (2016) Beware of unreliable Q2! A comparative study of regression metrics for predictivity assessment of QSAR models. J Chem Inf Model 56(10):1905–1913
132. Dobson CM (2004) Chemical space and biology. Nature 432(7019):824–828
133. Lipinski C, Hopkins A (2004) Navigating chemical space for biology and medicine. Nature 432(7019):855–861
134. Topliss JG (1972) Utilization of operational schemes for analog synthesis in drug design. J Med Chem 15(10):1006–1011
135. Griffen E, Leach AG, Robb GR etal (2011) Matched molecular pairs as a medicinal chemis­try tool. J Med Chem 54(22):7739–7750
136. Stewart KD, Shiroda M, James CA (2006) Drug Guru: a computer software program for drug design using medicinal chemistry rules. Bioorg Med Chem 14(20):7011–7022
137. Humbeck L, Weigang S, Schäfer T etal (2018) CHI PMUNK: a virtual synthesizable small­molecule library for medicinal chemistry, exploitable for protein-protein interaction modula­tors. ChemMedChem 13(6):532–539
138. Schneider G, Lee ML, Stahl M etal (2000) De novo design of molecular architectures by evo­lutionary assembly of drug-derived building blocks. J Comput Aided Mol Des 14(5):487–494
139. Salakhutdinov R (2015) Learning deep generative models. Annu Rev Stat Appl 2(1):361–385
140. Gordeeva EV, Molchanova MS, Zerov NS (1990) General methodology and computer program for the exhaustive restoring of chemical structures by molecular connectivity indexes. Solution of the inverse problem in QSAR/QSPR.Tetrahedron Comput Methodol 3(6):389–415
141. Skvortsova MI, Stankevich IV, Zerov NS (1992) Generation of molecular structures of poly­condensed benzenoid hydrocarbons using the randic index. J Struct Chem 33(3):416–422
142. Skvortsova MI, Baskin II, Slovokhotova OL etal (1993) Inverse problem in QSAR/QSPR studies for the case of topological indexes characterizing molecular shape (Kier indices). J Chem Inf Model 33:630–634
A. V. Geevarghese
Explainable Articial Intelligence inDrug Discovery
143. Vanhaelen Q, Lin Y-C, Zhavoronkov A (2020) The advent of generative chemistry. ACS Med Chem Lett 11(8):1496–1505
144. Weininger D (1988) SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules. J Chem Inf Model 28(1):31–36
145. Segler MHS, Kogej T, Tyrchan C etal (2018) Generating focused molecule libraries for drug discovery with recurrent neural networks. ACS Cent Sci 4(1):120–131
146. Merk D, Friedrich L, Grisoni F etal (2018) De novo design of bioactive small molecules by articial intelligence. Mol Inform 37(1–2):1700153
147. Olivecrona M, Blaschke T, Engkvist O etal (2017) Molecular de-novo design through deep reinforcement learning. J Cheminform. 9:48. https://doi.org/10.1186/s13321- 017- 0235- x
148. Blaschke T, Engkvist O, Bajorath J et al (2020) Memory-assisted reinforcement learn­ing for diverse molecular de novo design. J Cheminform 12:68. https://doi.org/10.1186/
s13321- 020- 00473- 0
149. Popova M, Isayev O, Tropsha A (2018) Deep reinforcement learning for de novo drug design. Sci Adv 4:eaap 7885
150. Gomez-Bombarelli R, Wei JN, Duvenaud D etal (2018) Automatic chemical design using a data-driven continuous representation of molecules. ACS Cent Sci 4(2):268–276
151. Maziarka Ł, Pocha A, Kaczmarczyk J etal (2018) Mol-CycleGAN: a generative model for molecular optimization. J Cheminform 12:2
152. Li Y, Zhang L, Liu Z (2018) Multi-objective de novo drug design with conditional graph generative model. J Cheminform 10:33. https://doi.org/10.1186/s13321- 018- 0287- 6
153. Khemchandani Y, O’Hagan S, Samanta S etal (2020) DeepGraphMolGen, a multi-objective, computational strategy for generating molecules with desirable properties: a graph convolu­tion and reinforcement learning approach. J Cheminform 12(1):1–17
154. Mendez-Lucio O, Baillif B, Clevert D-A etal (2020) De novo generation of hit-like mol­ecules from gene expression signatures using articial intelligence. Nat Commun 11(1):10
155. Nicolaou CA, Brown N (2013) Multi-objective optimization methods in drug design. Drug Discov Today Technol 10(3):e427–e435
156. Cruz-Monteagudo M, Borges F, Cordeiro MNDS (2008) Desirability-based multiobjec­tive optimization for global QSAR studies: application to the design of novel NSAIDs with improved analgesic, antiinammatory, and ulcerogenic proles. J Comput Chem 29(14):2445–2459
157. Perez-Castillo Y, Sanchez-Rodriguez A, Tejera E et al (2018) A desirability-based multi objective approach for the virtual screening discovery of broad-spectrum anti-gastric cancer agents. PLoS One 13(2):e0192176
158. Spiegel JO, Durrant JD (2020) AutoGrow4: an open-source genetic algorithm for de novo drug design and lead optimization. J Cheminform 12(1):25
159. Skalic M, Sabbadin D, Sattarov B etal (2019) From target to drug: generative modeling for the multimodal structure-based ligand design. Mol Pharm 16(10):4282–4291
160. Xu M, Ran T, Chen H (2020) De novo molecule design through molecular generative model conditioned by 3D information of protein binding sites. ChemRxiv. https://doi.org/10.26434/
chemrxiv.13498332.v1
161. Jeon W, Kim D (2020) Autonomous molecule generation using reinforcement learning and docking to develop potential novel inhibitors. Sci Rep 10(1):22104
162. Friedrich L, Rodrigues T, Neuhaus CS et al (2016) From complex natural products to simple synthetic mimetics by computational de novo design. Angew Chem Int Ed Engl 55(23):6789–6792
163. Sutskever I, Vinyals O, Le QV (2014) Sequence to sequence learning with neural networks. In: Ghahramani Z, Welling M, Cortes C etal (eds) Adv. neural inf. proc. sys, vol 27. Curran Associates, Inc., Montreal, pp3104–3112
164. Devlin J, Chang M-W, Lee K etal (2018) BERT: pre-training of deep bidirectional transform­ers for language understanding. arXiv [cs. CL]
133
134
165. Cadeddu A, Wylie EK, Jurczak J etal (2014) Organic chemistry as a language and the impli­cations of chemical linguistics for structural and retrosynthetic analyses. Angew Chem Int Ed Engl 53(31):8108–8112
166. Liu B, Ramsundar B, Kawthekar P etal (2017) Retrosynthetic reaction prediction using neu­ral sequence-to-sequence models. ACS Cent Sci 3(10):1103–1113
167. Baylon JL, Cilfone NA, Gulcher JR etal (2019) Enhancing retrosynthetic reaction prediction with deep learning using multiscale reaction classication. J Chem Inf Model 59(2):673–688
168. Coley CW, Rogers L, Green WH etal (2017) Computer-assisted retrosynthesis based on molecular similarity. ACS Cent Sci 3(12):1237–1245
169. Raccuglia P, Elbert KC, Adler PDF etal (2016) Machine-learning-assisted materials discov­ery using failed experiments. Nature 533(7601):73–76
170. Coley CW, Barzilay R, Jaakkola TS etal (2017) Prediction of organic reaction outcomes using machine learning. ACS Cent Sci 3(5):434–443
171. Coley CW. The open reaction database. [cited 2020 Dec 15]. https://docs.open- reaction-
database.org/
172. Satoh H, Funatsu K (1995) SOPHIA, a knowledge base-guided reaction prediction system— utilization of a knowledge base derived from a reaction database. J Chem Inf Comput Sci 35(1):34–44
173. Wei JN, Duvenaud D, Aspuru-Guzik A (2016) Neural networks for the prediction of organic chemistry reactions. ACS Cent Sci 2(10):725–732
174. Bradshaw J, Kusner MJ, Paige B etal (2018) A generative model for electron paths. arXiv [physics.chem-ph]
175. Do K, Tran T, Venkatesh S (2019) Graph transformation policy network for chemical reaction prediction. In: Proceedings of the 25th ACM SIGKDD international conference on knowl­edge discovery & data mining. Association for Computing Machinery, Anchorage, AK, pp750–760
176. Lipton ZC (2017) The doctor just won’t accept that! Preprint at https://arxiv.org/
abs/1711.08037
177. Goodman B, Flaxman S (2017) European Union regulations on algorithmic decision-making and a ‘right to explanation’. AI Mag 38:50–57
178. Ikebata H, Hongo K, Isomura T, Maezono R, Yoshida R (2017) Bayesian molecular design with a chemical language model. J Comput Aided Mol Des 31:379–391
179. Nagarajan D etal (2018) Computational antimicrobial peptide design and evaluation against multidrug-resistant clinical isolates of bacteria. J Biol Chem 293:3492–3509
180. Müller AT, Hiss JA, Schneider G (2018) Recurrent neural network model for constructive peptide design. J Chem Inf Model 58:472–479
181. Jiménez-Luna J, Cuzzolin A, Bolcato G, Sturlese M, Moro S (2020) A deep-learning approach toward rational molecular docking protocol selection. Molecules 25:2487
182. Rogers D, Hahn M (2010) Extended-connectivity ngerprints. J Chem Inf Model 50:742–754
183. Awale M, Reymond J-L (2014) Atom pair 2D-ngerprints perceive 3D-molecular shape and pharmacophores for very fast virtual screening of ZINC and GDB-17. J Chem Inf Model 54:1892–1907
184. Todeschini R, Consonni V (2010) New local vertex invariants and molecular descriptors based on functions of the vertex degrees. MATCH Commun Math Comput Chem 64:359–372
185. Katritzky AR, Gordeeva EV (1993) Traditional topological indexes vs electronic, geometri­cal, and combined molecular descriptors in QSAR/QSPR research. J Chem Inf Comput Sci 33:835–857
186. Sahigara F etal (2012) Comparison of different approaches to dene the applicability domain of QSAR models. Molecules 17:4791–4810
187. Mathea M, Klingspohn W, Baumann K (2016) Chemoinformatic classication methods and their applicability domain. Mol Inform 35:160–180
A. V. Geevarghese
Explainable AI forBig Data Control
RajanikanthAluvalu , SwapnaMudrakola , PradoshChandra Patnaik, UmaMaheswariV , andKrishnaKeerthiChennam
Abstract Digital transformation of the world has become automated scenarios in
our daily lives and made our lives easy and smart. The data collection, storage and maintenance have turned into big data. Big data in the digital industry has brought some problems from storage structure to data extraction. Big data analysis uses statistical, algebraic, probability, and articial intelligence (AI) concepts. Explained AI (XAI) is a process to explain the reason for the output predictions or results. XAI concepts are used to build automated applications and self-reason for the steps taken and justify the next sequence. AI algorithms are black box approaches and XAI are white box approaches and transparent in decision-making and interpretation of the results. Big data control requires a specic reason for insights generated using AI from a huge database. This chapter insights knowledge about the explainable AI and big data control challenges. Detailed surveys on the XAI applications and XAI tech­niques and case studies are discussed.
Keywords Explainable AI (XAI) · Articial intelligence · Machine learning · Reasoning
R. Aluvalu (*) Symbiosis Institute of Technology, Hyderabad Campus, Hyderabad, Telangana, India
Symbiosis International (Deemed University), Pune, India e-mail: rajanikanth.aluvalu@ieee.org
S. Mudrakola Department of AIML, Aurora University, Uppal, Hyderabad, India
P. Chandra Patnaik Aurora’s PG College, Nampally, Hyderabad, India
U. M. V Department of CSE, Chaitanya Bharathi Institute of Technology, Hyderabad, India
K. K. Chennam Vasavi Engineering College, Hyderabad, India
Ltd. 2024 R. Aluvalu et al. (eds.), Explainable AI in Health Informatics, Computational Intelligence Methods and Applications,
https://doi.org/10.1007/978-981-97-3705-5_7
135© The Author(s), under exclusive license to Springer Nature Singapore Pte