AlphaGenome splice site usage score

Score splice-site usage with AlphaGenome on three segments (left_flank, intron_core, right_flank).

License: AlphaGenome uses Apache-2.0 for code and Custom (AlphaGenome Terms of Use) for model weights and has restrictions around commercial use and may require explicit attribution when utilized. Model weights are gated and require accepting the provider’s terms and authenticating with a HuggingFace token. Please refer to the code license and model weights license for full terms.

This constraint is open source. Any third-party models, product names, or trademarks referenced are the property of their respective owners, and Proto is not affiliated with them.

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proto-bio/proto-language/proto_language/constraint/rna_splicing/alphagenome_splice_site_usage.py

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@article{avsec2026alphagenome,
  title={Advancing regulatory variant effect prediction with AlphaGenome},
  author={Avsec, {\v{Z}}iga and Latysheva, Natasha and Cheng, Jun and Novati, Guido and Taylor, Kyle R and Ward, Tom and Bycroft, Clare and Nicolaisen, Lauren and Arvaniti, Eirini and Pan, Joshua and Thomas, Raina and Dutordoir, Vincent and Perino, Matteo and De, Soham and Karollus, Alexander and Gayoso, Adam and Sargeant, Toby and Mottram, Anne and Wong, Lai Hong and Drot{\'a}r, Pavol and Kosiorek, Adam and Senior, Andrew and Tanburn, Richard and Applebaum, Taylor and Basu, Souradeep and Hassabis, Demis and Kohli, Pushmeet},
  journal={Nature},
  year={2026},
  volume={649},
  number={8099},
  pages={1206--1218},
  doi={10.1038/s41586-025-10014-0}
}

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Score AlphaGenome SSU at selected positions in a three-part target.

Each input tuple contains three DNA sequences (left_flank, intron_core, right_flank) which are concatenated into a target, wrapped with cassette contexts, and integrated into a genomic context for AlphaGenome prediction.

API Reference

ConfigAlphaGenomeSpliceSiteUsageConfig Source

Configuration for AlphaGenome splice-site-usage scoring.

Takes three segments (left_flank, intron_core, right_flank), concatenates them into a target sequence, wraps with cassette contexts, and integrates into a genomic context for AlphaGenome prediction. Splice positions are specified relative to the concatenated target sequence.

genomic_context · string · required

Genomic context sequence for cassette integration (e.g., AAVS1 safe harbor locus).

cassette_left_context · string · required

Left flanking context for the cassette (plasmid/gene sequence 5’ of the target).

cassette_right_context · string · required

Right flanking context for the cassette (plasmid/gene sequence 3’ of the target).

ontology_terms · List[string] · required

AlphaGenome ontology term(s) to score.

splice_pos · List[integer] · required

0-indexed position(s) in the concatenated target to evaluate.

direction · enum · default: "max"

‘max’ returns 1-mean(SSU); ‘min’ returns mean(SSU).

Options: max, min

strand · enum · default: "positive"

Track strand subset to aggregate over.

Options: positive, negative, all

model_version · string · default: "all_folds"

AlphaGenome model version.

organism · enum · default: "human"

Organism for AlphaGenome prediction.

Options: human, mouse

device · string · default: "cuda"

Device for AlphaGenome prediction.

prediction_timeout · integer · default: "3600"

Timeout (seconds) for each AlphaGenome prediction call.

ReturnsConstraintOutput

One result per input. score is in [0.0, 1.0] (interpretation depends on direction). metadata carries the selected tracks plus alphagenome_splice_site_usage_raw and _score.

Usage

python

from proto_language.core import Constraint
from proto_language.constraint import alphagenome_splice_site_usage, AlphaGenomeSpliceSiteUsageConfig

constraint = Constraint(
    inputs=[segment],
    function=alphagenome_splice_site_usage,
    function_config=AlphaGenomeSpliceSiteUsageConfig(
        # Configure parameters here
    ),
)

scores = constraint.evaluate()

Metadata

Property	Value
Key	alphagenome-splice-site-usage
Function	alphagenome_splice_site_usage
Category	rna_splicing
Mode	discrete
Uses GPU	True
Supported Types	dna