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 ABodyBuilder-ML, with CDR loops modelled by ABlooper and side-chains modelled by PEARS, to generate a model structure of your antibody.
- 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, communicating the confidence you should have in our metric values
- 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 profiler, or if you use this software, 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 27th June 2022. We are now tracking 591 post Phase-I therapeutic Fvs.
NB: As of 27 June 2022, the TAP protocol was updated to use Fv models generated by ABodyBuilder-ML, our new machine-learning based version of ABodyBuilder that uses ABlooper for CDR modelling. 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 (27th June 2022) | Red Region (27th June 2022) |
|---|---|---|
| Total CDR Length (L) | 38 ≤ L ≤ 43 | L < 38 |
| 55 ≤ L ≤ 63 | L > 63 | |
| Patches of Surface Hydrophobicity (PSH) | 77.58 ≤ PSH ≤ 94.92 | PSH < 77.58 |
| 151.07 ≤ PSH ≤ 182.49 | PSH > 182.49 | |
| Patches of Positive Charge (PPC) | 1.30 ≤ PPC ≤ 3.71 | PPC > 3.71 |
| Patches of Negative Charge (PNC) | 1.97 ≤ PNC ≤ 3.65 | PNC > 3.65 |
| Structural Fv Charge Symmetry Parameter (SFvCSP) | -19.6 ≤ SFvCSP ≤ -4.95 | SFvCSP < -19.6 |
Please visit Thera-SAbDab to access our latest CST sequence data.
