The RESP AI model accelerates the identification of tight-binding antibodies.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 01 2023
28 01 2023
Historique:
received:
31
07
2022
accepted:
13
01
2023
pubmed:
29
1
2023
medline:
1
2
2023
entrez:
28
1
2023
Statut:
epublish
Résumé
High-affinity antibodies are often identified through directed evolution, which may require many iterations of mutagenesis and selection to find an optimal candidate. Deep learning techniques hold the potential to accelerate this process but the existing methods cannot provide the confidence interval or uncertainty needed to assess the reliability of the predictions. Here we present a pipeline called RESP for efficient identification of high affinity antibodies. We develop a learned representation trained on over 3 million human B-cell receptor sequences to encode antibody sequences. We then develop a variational Bayesian neural network to perform ordinal regression on a set of the directed evolution sequences binned by off-rate and quantify their likelihood to be tight binders against an antigen. Importantly, this model can assess sequences not present in the directed evolution library and thus greatly expand the search space to uncover the best sequences for experimental evaluation. We demonstrate the power of this pipeline by achieving a 17-fold improvement in the K
Identifiants
pubmed: 36709319
doi: 10.1038/s41467-023-36028-8
pii: 10.1038/s41467-023-36028-8
pmc: PMC9884274
doi:
Substances chimiques
Peptide Library
0
Antibodies
0
Antigens
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
454Subventions
Organisme : NIAID NIH HHS
ID : R21 AI158114
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM111941
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
MAbs. 2022 Jan-Dec;14(1):2020203
pubmed: 35133949
Patterns (N Y). 2021 Dec 09;3(2):100406
pubmed: 35199061
PLoS Comput Biol. 2021 Mar 29;17(3):e1008864
pubmed: 33780441
PLoS One. 2015 Nov 10;10(11):e0141287
pubmed: 26555596
Phys Chem Chem Phys. 2014 Aug 21;16(31):16719-29
pubmed: 24999761
Annu Rev Pathol. 2021 Jan 24;16:223-249
pubmed: 33197221
Biotechnol Prog. 1998 Jan-Feb;14(1):55-62
pubmed: 10858036
Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):E193-201
pubmed: 23277561
Bioinformatics. 2021 Jun 10;:
pubmed: 34110413
Bioinform Adv. 2022 Jun 17;2(1):vbac046
pubmed: 36699403
Bioinformatics. 2020 Jul 1;36(13):3996-4003
pubmed: 32321157
Nat Biomed Eng. 2021 Jun;5(6):600-612
pubmed: 33859386
Bioinformatics. 2018 Aug 1;34(15):2605-2613
pubmed: 29554211
Oncotarget. 2017 Oct 6;8(52):90215-90224
pubmed: 29163822
Sci Rep. 2021 Mar 12;11(1):5852
pubmed: 33712669
Nat Commun. 2021 Apr 23;12(1):2403
pubmed: 33893299
Nat Commun. 2022 Jul 1;13(1):3788
pubmed: 35778381
J Biomed Sci. 2020 Jan 2;27(1):1
pubmed: 31894001
PLoS Comput Biol. 2019 Aug 23;15(8):e1007207
pubmed: 31442220
Front Immunol. 2018 Oct 16;9:2278
pubmed: 30386328
J Proteome Res. 2020 Jun 5;19(6):2304-2315
pubmed: 32308001
Clin Dev Immunol. 2012;2012:980250
pubmed: 22474489
Protein Expr Purif. 2005 Aug;42(2):255-67
pubmed: 15946857
Methods Mol Biol. 2017;1529:265-277
pubmed: 27914056
Brief Bioinform. 2022 Jul 18;23(4):
pubmed: 35830864
Brief Bioinform. 2022 Jan 17;23(1):
pubmed: 34676398
Protein Cell. 2018 Jan;9(1):135-139
pubmed: 28488247
Patterns (N Y). 2022 May 18;3(7):100513
pubmed: 35845836
J Hematol Oncol. 2019 Sep 5;12(1):92
pubmed: 31488176
Sci Rep. 2017 Jul 17;7(1):5532
pubmed: 28717238
Protein Eng Des Sel. 2019 Dec 31;32(7):347-354
pubmed: 31504835
PLoS Comput Biol. 2022 Jun 27;18(6):e1010271
pubmed: 35759518
Protein Eng Des Sel. 2010 Aug;23(8):589-97
pubmed: 20513707
Nat Methods. 2019 Dec;16(12):1315-1322
pubmed: 31636460
Methods Mol Biol. 2015;1319:51-63
pubmed: 26060069
Science. 2018 Apr 27;360(6387):423-427
pubmed: 29700264
Brief Bioinform. 2020 Sep 25;21(5):1549-1567
pubmed: 31626279
Bioinformatics. 2020 Apr 1;36(7):2126-2133
pubmed: 31778140
Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3011-6
pubmed: 18287011
Nat Methods. 2019 Aug;16(8):687-694
pubmed: 31308553
Cold Spring Harb Perspect Biol. 2019 Dec 2;11(12):
pubmed: 30833455
Bioinformatics. 2021 May 17;37(7):992-999
pubmed: 32866236
Chem Soc Rev. 2018 Dec 10;47(24):9137-9157
pubmed: 30298157
Sci Rep. 2021 Oct 19;11(1):20685
pubmed: 34667200
PLoS Comput Biol. 2019 May 1;15(5):e1006980
pubmed: 31042706
PLoS Comput Biol. 2011 Oct;7(10):e1002195
pubmed: 22039361
Bioinformatics. 2018 Sep 1;34(17):2944-2950
pubmed: 29672675
J Chem Inf Model. 2020 Aug 24;60(8):3992-4004
pubmed: 32786513
Nat Protoc. 2006;1(2):755-68
pubmed: 17406305
MAbs. 2022 Jan-Dec;14(1):2008790
pubmed: 35293269
Nucleic Acids Res. 2021 Jul 2;49(W1):W431-W437
pubmed: 33956157
Methods Mol Biol. 2015;1319:65-78
pubmed: 26060070
Front Immunol. 2019 Oct 09;10:2365
pubmed: 31649674
J Biol Chem. 2013 Apr 26;288(17):11771-85
pubmed: 23417675
Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):E6506-14
pubmed: 26604307
Bioinformatics. 2021 Sep 21;:
pubmed: 34546288
Proc Natl Acad Sci U S A. 2021 Apr 13;118(15):
pubmed: 33876751
Bioinformatics. 2016 Jan 15;32(2):298-300
pubmed: 26424857
Curr Opin Struct Biol. 2016 Jun;38:163-73
pubmed: 27525816