Biomedical generative pre-trained based transformer language model for age-related disease target discovery.

aging biomarkers deep learning human aging therapeutic target discovery transformers

Journal

Aging
ISSN: 1945-4589
Titre abrégé: Aging (Albany NY)
Pays: United States
ID NLM: 101508617

Informations de publication

Date de publication:
22 09 2023
Historique:
received: 15 06 2023
accepted: 20 08 2023
medline: 9 10 2023
pubmed: 24 9 2023
entrez: 24 9 2023
Statut: ppublish

Résumé

Target discovery is crucial for the development of innovative therapeutics and diagnostics. However, current approaches often face limitations in efficiency, specificity, and scalability, necessitating the exploration of novel strategies for identifying and validating disease-relevant targets. Advances in natural language processing have provided new avenues for predicting potential therapeutic targets for various diseases. Here, we present a novel approach for predicting therapeutic targets using a large language model (LLM). We trained a domain-specific BioGPT model on a large corpus of biomedical literature consisting of grant text and developed a pipeline for generating target prediction. Our study demonstrates that pre-training of the LLM model with task-specific texts improves its performance. Applying the developed pipeline, we retrieved prospective aging and age-related disease targets and showed that these proteins are in correspondence with the database data. Moreover, we propose CCR5 and PTH as potential novel dual-purpose anti-aging and disease targets which were not previously identified as age-related but were highly ranked in our approach. Overall, our work highlights the high potential of transformer models in novel target prediction and provides a roadmap for future integration of AI approaches for addressing the intricate challenges presented in the biomedical field.

Identifiants

pubmed: 37742294
pii: 205055
doi: 10.18632/aging.205055
pmc: PMC10564439
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

9293-9309

Références

Brief Bioinform. 2022 Nov 19;23(6):
pubmed: 36156661
Age Ageing. 2013 May;42(3):352-9
pubmed: 23111338
Nat Methods. 2019 Apr;16(4):315-318
pubmed: 30923381
Expert Opin Investig Drugs. 2018 Mar;27(3):301-311
pubmed: 29448843
Front Aging Neurosci. 2019 Aug 07;11:209
pubmed: 31447666
J Clin Endocrinol Metab. 2004 Apr;89(4):1646-9
pubmed: 15070925
Aging (Albany NY). 2019 Nov 25;11(22):10771-10780
pubmed: 31767810
Nat Biotechnol. 2019 Sep;37(9):1038-1040
pubmed: 31477924
Mol Med Rep. 2019 Feb;19(2):759-770
pubmed: 30535440
Cell. 2013 Jun 6;153(6):1194-217
pubmed: 23746838
Bioinformatics. 2009 Jun 1;25(11):1422-3
pubmed: 19304878
Trends Pharmacol Sci. 2019 Aug;40(8):546-549
pubmed: 31279569
Mediators Inflamm. 2014;2014:292376
pubmed: 24523569
Healthcare (Basel). 2023 Mar 19;11(6):
pubmed: 36981544
Cureus. 2023 Mar 17;15(3):e36272
pubmed: 37073184
Nat Biotechnol. 2010 Dec;28(12):1248-50
pubmed: 21139605
Eur J Clin Invest. 2021 Nov;51(11):e13600
pubmed: 34076259
Ageing Res Rev. 2020 Jul;60:101050
pubmed: 32272169
J Clin Invest. 1995 Mar;95(3):1009-17
pubmed: 7883948
Cytokine Growth Factor Rev. 2001 Dec;12(4):361-73
pubmed: 11544105
Front Immunol. 2022 Jan 20;12:816515
pubmed: 35126374
Mol Pharm. 2018 Oct 1;15(10):4311-4313
pubmed: 30269508
Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:779-803
pubmed: 32997601
Signal Transduct Target Ther. 2022 Dec 16;7(1):391
pubmed: 36522308
Scand J Gastroenterol. 2017 May;52(5):551-557
pubmed: 28140695
Nature. 1993 Jan 7;361(6407):79-82
pubmed: 7678446
Aging (Albany NY). 2022 Mar 29;14(6):2475-2506
pubmed: 35347083
Front Aging. 2023 Mar 01;4:1057204
pubmed: 36936271
Aging Cell. 2017 Jun;16(3):594-597
pubmed: 28299908
Liver Int. 2018 Jun;38(6):1128-1138
pubmed: 29356312
Nat Aging. 2023 Mar;3(3):248-257
pubmed: 37118425
J Neurosci Res. 1999 Jul 15;57(2):153-65
pubmed: 10398293
Cancer Res. 2019 Oct 1;79(19):4801-4807
pubmed: 31292161
Sci China Life Sci. 2022 Dec;65(12):2354-2454
pubmed: 36066811
Science. 2003 Dec 5;302(5651):1704-9
pubmed: 14657486
Osteoporos Int. 2012 Mar;23(3):971-80
pubmed: 21656018
Med Ref Serv Q. 2020 Oct-Dec;39(4):382-387
pubmed: 33085945
Nucleic Acids Res. 2018 Jan 4;46(D1):D1083-D1090
pubmed: 29121237
Aging Cell. 2022 Jun;21(6):e13646
pubmed: 35645319
Front Aging Neurosci. 2022 Jun 28;14:914017
pubmed: 35837482
Oxid Med Cell Longev. 2017;2017:7941563
pubmed: 28874954
Rheumatology (Oxford). 2017 Mar 1;56(3):495-497
pubmed: 28082621
Breast Cancer Res. 2021 Jan 23;23(1):11
pubmed: 33485378
Endocrinol Metab Clin North Am. 2018 Dec;47(4):743-758
pubmed: 30390810
J Leukoc Biol. 1996 Jul;60(1):147-52
pubmed: 8699119
Aging (Albany NY). 2015 Sep;7(9):616-28
pubmed: 26342919
Mol Pharm. 2017 Sep 5;14(9):3098-3104
pubmed: 28703000
EMBO Rep. 2019 Oct 4;20(10):e47865
pubmed: 31531937
iScience. 2020 Jun 26;23(6):101199
pubmed: 32534441
J Clin Endocrinol Metab. 2003 Dec;88(12):5766-72
pubmed: 14671166
Nat Rev Neurol. 2016 Feb;12(2):95-105
pubmed: 26782333
Nat Aging. 2021 Jan;1(1):5-7
pubmed: 37118000
Kidney Int. 1985 Nov;28(5):722-7
pubmed: 2935672
Nat Rev Endocrinol. 2021 May;17(5):296-306
pubmed: 33603219
Signal Transduct Target Ther. 2020 Jun 10;5(1):90
pubmed: 32532965
J Gerontol A Biol Sci Med Sci. 2018 Oct 8;73(11):1482-1490
pubmed: 29340580
Hum Genet. 2001 Dec;109(6):678-80
pubmed: 11810281
Nat Rev Cancer. 2015 Jan;15(1):55-64
pubmed: 25533676

Auteurs

Diana Zagirova (D)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.

Stefan Pushkov (S)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.

Geoffrey Ho Duen Leung (GHD)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.

Bonnie Hei Man Liu (BHM)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.

Anatoly Urban (A)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.

Denis Sidorenko (D)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.

Aleksandr Kalashnikov (A)

Insilico Medicine AI Limited, Level 6, Unit 08, Block A, IRENA HQ Building, Masdar City, Abu Dhabi, UAE.

Ekaterina Kozlova (E)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.

Vladimir Naumov (V)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.

Frank W Pun (FW)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.

Ivan V Ozerov (IV)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.

Alex Aliper (A)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
Insilico Medicine AI Limited, Level 6, Unit 08, Block A, IRENA HQ Building, Masdar City, Abu Dhabi, UAE.

Alex Zhavoronkov (A)

Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
Insilico Medicine AI Limited, Level 6, Unit 08, Block A, IRENA HQ Building, Masdar City, Abu Dhabi, UAE.

Articles similaires

Humans Robotic Surgical Procedures Male Female Aged
Humans Hernias, Diaphragmatic, Congenital Case-Control Studies Prospective Studies Sweden

UK Foot and Ankle Thromboembolism (UK-FATE).

Jitendra Mangwani, Linzy Houchen-Wolloff, Karan Malhotra et al.
1.00
Humans Venous Thromboembolism Male Female United Kingdom

Classifications MeSH