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Insights into next generation sequencing guided antibody selection strategies

Erasmus, M Frank ; Ferrara, Fortunato ; D'Angelo, Sara ; Spector, Laura ; Leal-Lopes, Camila ; Teixeira, André A ; Sørensen, Jesper ; Nagpal, Suhani ; Perea-Schmittle, Kathryn ; Choudhary, Alok ; Honnen, William ; Calianese, David ; Antonio Rodriguez Carnero, Luis ; Cocklin, Simon ; Greiff, Victor ; Pinter, Abraham ; Bradbury, Andrew R M

Scientific reports, 2023-10, Vol.13 (1), p.18370-18370, Article 18370 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Insights into next generation sequencing guided antibody selection strategies
Autor: Erasmus, M Frank ; Ferrara, Fortunato ; D'Angelo, Sara ; Spector, Laura ; Leal-Lopes, Camila ; Teixeira, André A ; Sørensen, Jesper ; Nagpal, Suhani ; Perea-Schmittle, Kathryn ; Choudhary, Alok ; Honnen, William ; Calianese, David ; Antonio Rodriguez Carnero, Luis ; Cocklin, Simon ; Greiff, Victor ; Pinter, Abraham ; Bradbury, Andrew R M
Assuntos: Affinity ; Antibodies ; Antibodies - genetics ; Antigens ; Cloning ; Epitopes ; High-Throughput Nucleotide Sequencing - methods ; Machine learning ; Next-generation sequencing ; Severe acute respiratory syndrome coronavirus 2 ; Yeast
É parte de: Scientific reports, 2023-10, Vol.13 (1), p.18370-18370, Article 18370
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: Therapeutic antibody discovery often relies on in-vitro display methods to identify lead candidates. Assessing selected output diversity traditionally involves random colony picking and Sanger sequencing, which has limitations. Next-generation sequencing (NGS) offers a cost-effective solution with increased read depth, allowing a comprehensive understanding of diversity. Our study establishes NGS guidelines for antibody drug discovery, demonstrating its advantages in expanding the number of unique HCDR3 clusters, broadening the number of high affinity antibodies, expanding the total number of antibodies recognizing different epitopes, and improving lead prioritization. Surprisingly, our investigation into the correlation between NGS-derived frequencies of CDRs and affinity revealed a lack of association, although this limitation could be moderately mitigated by leveraging NGS clustering, enrichment and/or relative abundance across different regions to enhance lead prioritization. This study highlights NGS benefits, offering insights, recommendations, and the most effective approach to leverage NGS in therapeutic antibody discovery.
Editor: England: Nature Publishing Group
Idioma: Inglês;Norueguês

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Insights into next generation sequencing guided antibody selection strategies

England: Nature Publishing Group

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