Humanize antibodies with optimal V-gene matching. Learn more
What is HuMatch?
HuMatch performs joint humanization of paired antibody heavy- and light-chain variable domains. It combines gene-specific germline-likeness data with three lightweight convolutional neural networks:
- CNN-H scores the heavy chain against seven human V-gene families.
- CNN-L scores the light chain against ten lambda and seven kappa families.
- CNN-P scores whether the heavy/light combination resembles a naturally paired human antibody.
ProteinIQ runs HuMatch 1.0.1 from the reviewed source revision and uses the model weights and germline arrays published with Zenodo record 13764771.
How to use HuMatch online
ProteinIQ runs HuMatch online for a paired antibody variable domain. Submit one heavy-chain and one light-chain sequence, choose the humanization targets, then receive humanized sequences, selected V-gene families, CNN scores, edit counts, the native HuMatch CSV, and a reproducibility record for the run.
Inputs
| Input | Requirement |
|---|---|
Heavy Chain (VH) | One complete antibody heavy-chain variable domain, 50-200 standard amino acids |
Light Chain (VL) | One complete antibody light-chain variable domain, 50-200 standard amino acids |
Raw sequence text and single-record FASTA are accepted. Both inputs must use the 20 standard amino-acid one-letter codes. Lowercase input is normalized to uppercase. Ambiguous residues, gaps, stop symbols, and multiple FASTA records in one slot are rejected.
ANARCI must be able to recognize and number both variable domains. A protein-like sequence that is not an antibody variable domain may pass the alphabet and length checks but fail during numbering. For numbering without humanization, run ANARCI.
Settings
Germline-likeness targets
The heavy- and light-chain targets default to 0.40, matching HuMatch. These
control the first mutation phase independently for each chain.
CNN targets
The heavy-chain, light-chain, and pairing targets each default to 0.95.
Higher targets request more human-like designs but may require more
substitutions or may not be reachable within the edit threshold.
Mutation controls
Maximum total edit distancedefaults to60across the paired heavy and light chains. HuMatch applies its initial germline-likeness mutations before checking this stopping threshold, so a returned best design can occasionally exceed it.Preserve CDR regionsis enabled by default and excludes IMGT CDR1, CDR2, and CDR3 positions from both mutation phases.
Target V-gene families
Automatic selection uses the highest-scoring human family for each submitted chain. Advanced runs can force HV1-HV7 for the heavy chain or KV1-KV7 / LV1-LV10 for the light chain.
Fixed IMGT positions
Enter comma-separated positions such as 9, 81A, 120 to prevent HuMatch from
changing those positions in either mutation phase. Heavy- and light-chain
lists are configured separately.
Output options
HuMatch's native CSV is always retained. A run can additionally request a TSV or JSON conversion. The sequence-comparison option adds a FASTA file containing the original and humanized heavy and light chains.
Results
The Results table contains one row per chain:
| Column | Meaning |
|---|---|
Original Sequence | Submitted variable-domain sequence |
Humanized Sequence | HuMatch design with padding removed |
Target V-Gene Family | Selected HV, KV, or LV family |
CNN Humanness Score | Probability assigned to the selected chain family |
Edits | Substitutions in that chain |
CNN Pairing Score | Probability that the paired design resembles natural human pairing |
Total Paired Edits | Source aggregate edit count across both chains |
Targets Reached | Whether all three configured CNN targets were reached |
Warning | Visible explanation when targets are unmet or the source result exceeds the edit stopping threshold |
Downloadable files
humatch-results.csv: Native HuMatch result withHumatch_H,Humatch_L,Edit,HV,LV,CNN_H,CNN_L, andCNN_Phumatch-config.yaml: Exact effective HuMatch configurationhumatch-provenance.json: Source, ANARCI, model-data, runtime, and setting provenancehumatch-run.log: HuMatch standard output and diagnostic messageshumatch-sequence-comparison.fasta: Optional original/humanized sequence comparisonhumatch-results.tsvorhumatch-results.json: Optional converted result
How humanization works
HuMatch first aligns each variable domain to 200 IMGT-numbered positions with ANARCI. It then applies two mutation phases.
- Germline-likeness phase: Common residues for the selected target V-gene family are introduced until each chain reaches its configured germline target.
- CNN-guided phase: HuMatch evaluates possible single substitutions and chooses changes that jointly improve the heavy-chain, light-chain, and pairing scores.
By default, IMGT CDR1, CDR2, and CDR3 positions are excluded from both phases. Humanization stops when all configured CNN targets are reached, the edit stopping threshold is crossed, or no novel design can be found. If every target cannot be reached, HuMatch returns the best-scoring design it observed and ProteinIQ reports a warning.
Limitations
- HuMatch evaluates sequence behavior; it does not model three-dimensional structures or binding affinity.
- CDR preservation reduces the chance of changing binding determinants but cannot guarantee preserved affinity or specificity.
- V-gene families with less training data may have less reliable classification scores.
- A high CNN-P score is a sequence-based pairing signal, not an experimental stability measurement.
- Designs should be reviewed structurally and validated experimentally before therapeutic use.
