How similar is your antibody to clinical-stage therapeutics?
- To use this application, you only require an amino acid antibody variable domain heavy and light chain sequence.
- The Therapeutic Antibody Profiler (TAP) compares your antibody variable domain sequence against five developability guidelines derived from clinical-stage therapeutic values.
- TAP now uses ABodyBuilder2 (*) to generate a model structure of your antibody.
(*)NB: ABodyBuilder-ML has been deprecated as ABodyBuilder2 is now our main tool for antibody structure modelling. This will have an effect on computed TAP scores and thresholds for flagging. To stay up-to-date with any new changes to our tools, follow our Twitter account.
- TAP then calculates the following properties (explained in the paper) to see if your antibody design is commenserate with those of clinical-stage therapeutics:
- Total CDR Length
- Patches of Surface Hydrophobicity (PSH) metric across the CDR Vicinity
- Patches of Positive Charge (PPC) metric across the CDR Vicinity
- Patches of Negative Charge (PNC) metric across the CDR Vicinity
- Structural Fv Charge Symmetry Parameter (SFvCSP)
- TAP also outputs...
- An interactive representation of your antibody model, allowing you to visualise hydrophobic/charge patches on the Van der Waals surface. The model is downloadable.
- A representation showing predicted model accuracy from ABodyBuilder2
- Sequence liabilities likely to lead to post- or co-translational modification
- For a sample TAP output, please click here. More information about the guidelines and more resources can be found here.
For a full description of the TAP metrics, please refer to: Raybould MIJ, et al. Five Computational Developability Guidelines for Therapeutic Antibody Profiling. PNAS. (2019)
Please cite our paper "Five Computational Developability Guidelines for Therapeutic Antibody Profiling" if making use of these datasets.
- The 242 Clinical-Stage Therapeutics (CST) models that set the TAP Guidelines in the PNAS paper can be found here.
- The 242 CST sequences can be found in the paper SI here (Dataset S2).
- The TAP Guidelines were last updated on 30th January 2023. We are now tracking 644 post Phase-I therapeutic Fvs.
NB: 30th January 2023, the TAP protocol was updated to use Fv models generated by ABodyBuilder2, our new version of ABodyBuilder that is part of ImmuneBuilder, a set of deep-learning models for structure prediction of immune proteins, including antibodies, nanobodies, and T-cell receptors (TCRs). TAP scores and therapeutic thresholds have changed accordingly. Please avoid interpreting the results from previous TAP runs against these new thresholds; instead resubmit your sequences to TAP to ensure the modelling methodology is consistent
| Property | Amber Region (30th January 2023) | Red Region (30th January 2023) |
|---|---|---|
| Total CDR Length (L) | 37 ≤ L ≤ 42 | L < 37 |
| 55 ≤ L ≤ 63 | L > 63 | |
| Patches of Surface Hydrophobicity (PSH) | 95.72 ≤ PSH ≤ 110.71 | PSH < 95.72 |
| 168.82 ≤ PSH ≤ 207.09 | PSH > 207.09 | |
| Patches of Positive Charge (PPC) | 1.34 ≤ PPC ≤ 4.27 | PPC > 4.27 |
| Patches of Negative Charge (PNC) | 1.95 ≤ PNC ≤ 4.43 | PNC > 4.43 |
| Structural Fv Charge Symmetry Parameter (SFvCSP) | -30.60 ≤ SFvCSP ≤ -6.0 | SFvCSP < -30.60 |
Please visit Thera-SAbDab to access our latest CST sequence data.
