ImmunoSeq
1 Introduction
ImmunoSeq1 is an interpretable and practical antibody immunogenicity prediction tool built on the biological principle of immune tolerance, which is dedicated to evaluating the immunogenicity risk of antibody sequences. Based on paired human and mouse antibody sequences as well as human protein sequences from the Observed Antibody Space2 (OAS) database, the tool constructs a k-mer (k=8–12) peptide library. Among them, the human peptide library serves as the positive reference library, and the mouse peptide library acts as the negative control library. The Hit Rate is calculated by summing the scores of positive matches (+1.0) and penalty scores of negative matches (−0.2), and then dividing the total sum by the number of all peptide fragments. A higher Hit Rate indicates a lower risk of inducing anti-drug antibody (ADA) responses. Furthermore, ImmunoSeq enables residue-level resolution analysis and can accurately pinpoint immunogenic hotspot regions within antibody sequences.
Figure 1. Technical framework of ImmunoSeq.
Figure 2. Correlation plot between Hit Rate and ADA% of therapeutic antibodies.
Figure 3. Distribution of Hit Rate across different species of therapeutic antibodies.
2 Parameters
- Heavy Chain Sequence：Fv protein sequence of antibody heavy chain.
- Light Chain Sequence：Fv protein sequence of antibody light chain.
3 Results Explanation
- Hit Rate: Immunogenicity hit rate. A higher value indicates a lower risk of anti-drug antibody (ADA) generation.
- Immunogenicity hotspot region plot
Figure 4. Example plot of immunogenicity hotspot regions.
4 Reference
[1] Kovaltsuk, A. et al. Observed Antibody Space: A Resource for Data Mining Next-Generation Sequencing of Antibody Repertoires. The Journal of Immunology 201, 2502–2509. https://doi.org/10.4049/jimmunol.1800708