AbDiver

AbDiver enables comparison of query antibody sequences to hundreds of millions of human antibody sequences from next-generation sequencing (NGS) datasets to inform rational therapeutic antibody design.

Key Features:

• Natural sequence comparison: Contrasts query therapeutic antibody sequences against naturally observed variants derived from NGS datasets containing hundreds of millions of human antibody sequences to provide a mutational roadmap.
• Positional variability analysis: Provides precomputed positional variability statistics derived from multiple independent studies to indicate common and rare mutations at each residue position.
• Full variable-region retrieval: Retrieves close full variable-region sequence matches from natural repertoires to identify naturally occurring sequences similar to queries.
• CDR3 and clonotype matching: Retrieves matching CDR3 regions and clonotypes to identify shared critical functional domains.
• Performance evaluation: Demonstrated retrieval of relevant results across use-cases for a dataset of 742 therapeutic antibodies.

Scientific Applications:

• Rational therapeutic antibody design: Informs design decisions by mapping observed natural variation onto therapeutic candidates.
• Mutation selection for engineering: Guides selection of tolerated or naturally observed mutations during antibody engineering.
• CDR3 and clonotype analysis: Supports identification of naturally occurring CDR3 sequences and clonotypes for functional and lineage studies.
• Exploration of mutation space: Enables large-scale exploration of antibody mutation landscapes via sequence-level matches and positional variability statistics.

Methodology:

Uses next-generation sequencing (NGS) datasets of hundreds of millions of human antibody sequences; computes positional variability statistics from multiple independent studies; performs sequence comparisons to retrieve full variable-region matches and CDR3/clonotype matches; validated on a dataset of 742 therapeutic antibodies.