Skip to main content Accessibility help
×
Hostname: page-component-76fb5796d-25wd4 Total loading time: 0 Render date: 2024-04-25T10:10:25.166Z Has data issue: false hasContentIssue false

6 - Artificial Intelligence in Alzheimer’s Drug Discovery

from Section 1 - Advancing Alzheimer’s Disease Therapies in a Collaborative Science Ecosystem

Published online by Cambridge University Press:  03 March 2022

Jeffrey Cummings
Affiliation:
University of Nevada, Las Vegas
Jefferson Kinney
Affiliation:
University of Nevada, Las Vegas
Howard Fillit
Affiliation:
Alzheimer’s Drug Discovery Foundation
Get access

Summary

Drug discovery and development pipelines are timely consuming and expensive, depending on numerous factors. Artificial intelligence (AI) tools are increasingly being applied in drug discovery for Alzheimer’s disease (AD). In the “big data” era, AI offers cutting-edge applications of informatics and computational tools for re-defining disease biology, discovering new therapeutics, and identifying novel targets with the least errors. The application of AI has the potential to enhance the pipeline across all stages of drug discovery and reduce failure rates in drug development for AD. In this chapter, we introduce AI techniques accessible for accelerating drug discovery. We summarize representation learning, machine learning, and deep learning toolboxes, available for drug discovery. We illustrate the application of AI for target identification, evaluation of pharmacokinetic properties (i.e., brain penetration), safety, and identification of biomarkers in clinical trials. We discuss current challenges and future directions of AI-based solutions for drug discovery. Rapidly developing, powerful and innovative AI technologies can expedite drug discovery and development for AD.

Type
Chapter
Information
Alzheimer's Disease Drug Development
Research and Development Ecosystem
, pp. 62 - 72
Publisher: Cambridge University Press
Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Hippius, H, Neundorfer, G. The discovery of Alzheimer’s disease. Dialogues Clin Neurosci 2003; 5: 101–8.Google Scholar
Corriveau, RA, Koroshetz, WJ, Gladman, JT, et al. Alzheimer’s Disease-Related Dementias Summit 2016: national research priorities. Neurology 2017; 89: 2381–91.Google Scholar
Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement 2016; 12: 459509.Google Scholar
Alzheimer’s Association. 2020 Alzheimer’s disease facts and figures. Alzheimers Dement 2020; 17: 327406.Google Scholar
Cummings, JL, Morstorf, T, Zhong, K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther 2014; 6: 37.CrossRefGoogle ScholarPubMed
Avorn, J. The $2.6 billion pill: methodologic and policy considerations. N Engl J Med 2015; 372: 1877–9.CrossRefGoogle ScholarPubMed
Fleming, N. How artificial intelligence is changing drug discovery. Nature 2018; 557: S55–7.CrossRefGoogle ScholarPubMed
Zhou, Y, Wang, F, Tang, J, et al. Artificial intelligence in COVID-19 drug repurposing. Lancet Digit Health 2020; 2: E667–76.Google ScholarPubMed
Vamathevan, J, Clark, D, Czodrowski, P, et al. Applications of machine learning in drug discovery and development. Nat Rev Drug Discov 2019; 18: 463–77.CrossRefGoogle ScholarPubMed
Schneider, P, Walters, WP, Plowright, AT, et al. Rethinking drug design in the artificial intelligence era. Nat Rev Drug Discov 2020; 19: 353–64.Google Scholar
Beecham, GW, Bis, JC, Martin, ER, et al. The Alzheimer’s Disease Sequencing Project: study design and sample selection. Neurol Genet 2017; 3: e194.Google Scholar
Petersen, RC, Aisen, PS, Beckett, LA, et al. Alzheimer’s Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology 2010; 74: 201–9.Google Scholar
Wishart, DS, Feunang, YD, Guo, AC, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res 2018; 46: D1074–82.Google Scholar
Ursu, O, Holmes, J, Knockel, J, et al. DrugCentral: online drug compendium. Nucleic Acids Res 2017; 45: D932–9.CrossRefGoogle ScholarPubMed
Zhou, Y, Fang, J, Bekris, L, et al. AlzGPS: a genome-wide positioning systems platform to catalyze multi-omics for Alzheimer’s therapeutic discovery. Alzheimers Res Ther 2021; 13: 24.CrossRefGoogle Scholar
O’Boyle, NM. Towards a universal SMILES representation: a standard method to generate canonical SMILES based on the InChI. J Cheminform 2012; 4: 22.Google Scholar
Lipinski, CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 2004; 1: 337–41.Google Scholar
Rogers, D, Hahn, M. Extended-connectivity fingerprints. J Chem Inf Model 2010; 50: 742–54.Google Scholar
Jaeger, S, Fulle, S, Turk, S . Mol2vec: unsupervised machine learning approach with chemical intuition. J Chem Inf Model 2018; 58: 2735.CrossRefGoogle ScholarPubMed
LeCun, Y, Bengio, Y, Hinton, G. Deep learning. Nature 2015; 521: 436–44.CrossRefGoogle ScholarPubMed
Rumelhart, DE, Hinton, GE, Williams, RJ. Learning representations by back-propagating errors. Nature 1986; 323: 533–6.CrossRefGoogle Scholar
Cai, C, Guo, P, Zhou, Y, et al. Deep learning-based prediction of drug-induced cardiotoxicity. J Chem Inf Model 2019; 59: 1073–84.CrossRefGoogle ScholarPubMed
Wu, Z, Ramsundar, B, Feinberg, EN, et al. MoleculeNet: a benchmark for molecular machine learning. Chem Sci 2018; 9: 513–30.CrossRefGoogle ScholarPubMed
Pardridge, WM. Alzheimer’s disease drug development and the problem of the blood–brain barrier. Alzheimers Dement 2009; 5: 427–32.Google Scholar
Cheng, F, Li, W, Liu, G, et al. In silico ADMET prediction: recent advances, current challenges and future trends. Curr Top Med Chem 2013; 13: 1273–89.Google Scholar
Shen, J, Cheng, F, Xu, Y, et al. Estimation of ADME properties with substructure pattern recognition. J Chem Inf Model 2010; 50: 1034–41.Google Scholar
Shaker, B, Yu, MS, Song, JS, et al. LightBBB: computational prediction model of blood–brain-barrier penetration based on LightGBM. Bioinformatics 2021; 37:1135–9.CrossRefGoogle ScholarPubMed
Miao, R, Xia, LY, Chen, HH, et al. Improved classification of blood–brain-barrier drugs using deep learning. Sci Rep 2019; 9: 8802.Google Scholar
Saxena, D, Sharma, A, Siddiqui, MH, et al. Blood brain barrier permeability prediction using machine learning techniques: an update. Curr Pharm Biotechnol 2019; 20: 1163–71.Google Scholar
Cheng, F, Kovacs, IA, Barabasi, AL. Network-based prediction of drug combinations. Nat Commun 2019; 10: 1197.Google Scholar
Bakkar, N, Kovalik, T, Lorenzini, I, et al. Artificial intelligence in neurodegenerative disease research: use of IBM Watson to identify additional RNA-binding proteins altered in amyotrophic lateral sclerosis. Acta Neuropathol 2018; 135: 227–47.CrossRefGoogle Scholar
Wang, Q, Chen, R, Cheng, F, et al. A Bayesian framework that integrates multi-omics data and gene networks predicts risk genes from schizophrenia GWAS data. Nat Neurosci 2019; 22: 691–9.Google Scholar
Fang, J, Zhang, P, Wang, Q, et al. Network-based translation of GWAS findings to pathobiology and drug repurposing for Alzheimer’s disease. bioRxiv 2020;DOI: http://doi.org/10.1101/2020.01.15.20017160.Google Scholar
Cheng, F, Desai, RJ, Handy, DE, et al. Network-based approach to prediction and population-based validation of in silico drug repurposing. Nat Commun 2018; 9: 2691.Google Scholar
Greene, JA, Loscalzo, J. Putting the patient back together: social medicine, network medicine, and the limits of reductionism. N Engl J Med 2017; 377: 2493–9.Google Scholar
Zeng, X, Song, X, Ma, T, et al. Repurpose open data to discover therapeutics for COVID-19 using deep learning. J Proteome Res 2020; 19: 4624–36.CrossRefGoogle ScholarPubMed
Santos, R, Ursu, O, Gaulton, A, et al. A comprehensive map of molecular drug targets. Nat Rev Drug Discov 2017; 16: 1934.Google Scholar
Zeng, X, Zhu, S, Lu, W, et al. Target identification among known drugs by deep learning from heterogeneous networks. Chem Sci 2020; 11: 1775–97.Google Scholar
Zeng, X, Zhu, S, Liu, X, et al. deepDR: a network-based deep learning approach to in silico drug repositioning. Bioinformatics 2019; 35: 5191–8.CrossRefGoogle ScholarPubMed
Fang, J, Pieper, AA, Nussinov, R, et al. Harnessing endophenotypes and network medicine for Alzheimer’s drug repurposing. Med Res Rev 2020; 40: 2386–426.Google Scholar
Hampel, H, Williams, C, Etcheto, A, et al. A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer’s disease therapy: analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study. Alzheimers Dement (N Y) 2020; 6: e12013.Google Scholar
Simpraga, S, Alvarez-Jimenez, R, Mansvelder, HD, et al. EEG machine learning for accurate detection of cholinergic intervention and Alzheimer’s disease. Sci Rep 2017; 7: 5775.CrossRefGoogle ScholarPubMed
Park, JH, Cho, HE, Kim, JH, et al. Machine learning prediction of incidence of Alzheimer’s disease using large-scale administrative health data. NPJ Digit Med 2020; 3: 46.CrossRefGoogle ScholarPubMed
Ma, J, Yu, MK, Fong, S, et al. Using deep learning to model the hierarchical structure and function of a cell. Nat Methods 2018; 15: 290–8.Google Scholar
Cheng, F, Ma, Y, Uzzi, B, et al. Importance of scientific collaboration in contemporary drug discovery and development: a detailed network analysis. BMC Biol 2020; 18: 138.Google Scholar
Tasaki, S, Gaiteri, C, Mostafavi, S, et al. The molecular and neuropathological consequences of genetic risk for Alzheimer’s dementia. Front Neurosci 2018; 12: 699.Google Scholar
Cheng, F, Zhao, J, Wang, Y, et al. Comprehensive characterization of protein–protein interactions perturbed by disease mutations. Nat Genet 2021; 53: 342–53.Google Scholar
Swarup, V, Hinz, FI, Rexach, JE, et al. Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia. Nat Med 2019; 25: 152–64.Google Scholar
Wang, M, Li, A, Sekiya, M, et al. Transformative network modeling of multi-omics data reveals detailed circuits, key regulators, and potential therapeutics for Alzheimer’s disease. Neuron 2021; 109: 257–72.CrossRefGoogle ScholarPubMed
Xu, J, Zhang, P, Huang, Y, et al. Multimodal single-cell/nucleus RNA-sequencing data analysis uncovers molecular networks between disease-associated microglia and astrocytes with implications for drug repurposing in Alzheimer’s disease. Genome Res 2021;DOI: http://doi.org/10.1101/gr.272484.120.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×