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Bulk Humanize...

[!WARNING] This method is not meant for lead humanization. It is to test a simple humanization on a large number of candidates. Use a more thoughtful approach for a final lead.

To humanize multiple antibodies in a single batch, select the desired entries in the Project View, open the Edit menu, and select Bulk Humanize....

The Bulk Humanize modal provides configurable options to customize the humanization strategy across the selected entries:

  • Method:

  • Top Germline: Identifies the closest germline V and J genes using the Modifiable Residues Identity method and grafts germline residues at non-excluded positions. Germlines are selected using a deterministic 5-tier ranking hierarchy matching the Humanization workspace: (1) Modifiable % Identity, (2) Modifiable % Homology tie-breaker, (3) Full Sequence % Identity tie-breaker, (4) Full Sequence % Homology tie-breaker, and (5) Gene Name alphabetically.

  • Sapiens: Utilizes the deep learning Sapiens antibody language model to predict human residues for non-excluded positions (restricted to Human target species).

  • Target Species:

  • Select the target germline species (e.g. Human, Rhesus, Mouse, Rat, Rabbit, Pig, Alpaca, Dog, Cat) when using Top Germline. Automatically locked to Human when Sapiens is selected.

  • Exclusions:

  • Honegger: Excludes structural Honegger framework and CDR positions from modification, grafting only into standard humanized framework positions.

  • CDRs: Excludes only CDR residues based on the chosen CDR definition (North, IMGT, Kabat, Martin, or AHo), allowing all framework positions to be modified.

  • Vernier Zone Exclusions:

  • Optional checkbox to retain parental residues at the 30 classic Vernier zone positions (16 on Heavy Chain, 14 on Light Chain) to preserve CDR conformation and binding affinity.

  • Automatic VHH Hallmark Retention:

  • Single-domain VHH entries automatically preserve parental residues at hallmark solubility positions (IMGT 42, 49, 50, and 52) under both Top Germline and Sapiens, and under both Honegger and CDR exclusion modes.

  • Registration and Analysis:

  • Generated sequences are registered directly into the project database under <Parent>_Hum names for Top Germline or <Parent>_Sapiens names for Sapiens (bypassing the Engineering workspace).

  • Automatically enqueues a targeted background re-analysis run that processes only the newly created entries.