Looking for therapeutic antibodies in next-generation sequencing repositories

Recently it has become possible to query the great diversity of natural antibody repertoires using next-generation sequencing (NGS). These methods are capable of producing millions of sequences in a single experiment. Here we compare clinical-stage therapeutic antibodies to the ~1b sequences from 60...

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Huvudupphovsmän: Krawczyk, K, Raybould, M, Kovaltsuk, A, Deane, C
Materialtyp: Journal article
Publicerad: Taylor and Francis 2019
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author Krawczyk, K
Raybould, M
Kovaltsuk, A
Deane, C
author_facet Krawczyk, K
Raybould, M
Kovaltsuk, A
Deane, C
author_sort Krawczyk, K
collection OXFORD
description Recently it has become possible to query the great diversity of natural antibody repertoires using next-generation sequencing (NGS). These methods are capable of producing millions of sequences in a single experiment. Here we compare clinical-stage therapeutic antibodies to the ~1b sequences from 60 independent sequencing studies in the Observed Antibody Space database, which includes antibody sequences from NGS analysis of immunoglobulin gene repertoires. Of 242 post-Phase 1 antibodies, we found 16 with sequence identity matches of 95% or better for both heavy and light chains. There are also 54 perfect matches to therapeutic CDR-H3 regions in the NGS outputs, suggesting a nontrivial amount of convergence between naturally observed sequences and those developed artificially. This has potential implications for both the legal protection of commercial antibodies and the discovery of antibody therapeutics.
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spelling oxford-uuid:0fa7fc00-696e-414d-814b-a98a708fbb482022-03-26T09:52:20ZLooking for therapeutic antibodies in next-generation sequencing repositoriesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0fa7fc00-696e-414d-814b-a98a708fbb48Symplectic Elements at OxfordTaylor and Francis2019Krawczyk, KRaybould, MKovaltsuk, ADeane, CRecently it has become possible to query the great diversity of natural antibody repertoires using next-generation sequencing (NGS). These methods are capable of producing millions of sequences in a single experiment. Here we compare clinical-stage therapeutic antibodies to the ~1b sequences from 60 independent sequencing studies in the Observed Antibody Space database, which includes antibody sequences from NGS analysis of immunoglobulin gene repertoires. Of 242 post-Phase 1 antibodies, we found 16 with sequence identity matches of 95% or better for both heavy and light chains. There are also 54 perfect matches to therapeutic CDR-H3 regions in the NGS outputs, suggesting a nontrivial amount of convergence between naturally observed sequences and those developed artificially. This has potential implications for both the legal protection of commercial antibodies and the discovery of antibody therapeutics.
spellingShingle Krawczyk, K
Raybould, M
Kovaltsuk, A
Deane, C
Looking for therapeutic antibodies in next-generation sequencing repositories
title Looking for therapeutic antibodies in next-generation sequencing repositories
title_full Looking for therapeutic antibodies in next-generation sequencing repositories
title_fullStr Looking for therapeutic antibodies in next-generation sequencing repositories
title_full_unstemmed Looking for therapeutic antibodies in next-generation sequencing repositories
title_short Looking for therapeutic antibodies in next-generation sequencing repositories
title_sort looking for therapeutic antibodies in next generation sequencing repositories
work_keys_str_mv AT krawczykk lookingfortherapeuticantibodiesinnextgenerationsequencingrepositories
AT raybouldm lookingfortherapeuticantibodiesinnextgenerationsequencingrepositories
AT kovaltsuka lookingfortherapeuticantibodiesinnextgenerationsequencingrepositories
AT deanec lookingfortherapeuticantibodiesinnextgenerationsequencingrepositories