> ## Documentation Index
> Fetch the complete documentation index at: https://proto.evodesign.org/docs/llms.txt
> Use this file to discover all available pages before exploring further.

# AlphaGenome splice site usage score

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

<div class="page-hero">
  <img class="page-hero-banner" src="https://proto-bio.github.io/proto-assets/images/constraint/alphagenome-splice-site-usage/hero.png" alt="AlphaGenome splice site usage score" />
</div>

<Note>
  **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](https://github.com/google-deepmind/alphagenome_research/blob/main/LICENSE) and [model weights license](https://deepmind.google.com/science/alphagenome/model-terms) for full terms.
</Note>

<p class="entity-disclaimer">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.</p>

<hr class="entity-rule" />

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<a href="https://github.com/evo-design/proto-language/blob/d3b7822f74ea64747cc751a3b2ab1aa6b799ac47/proto_language/constraint/rna_splicing/alphagenome_splice_site_usage.py#L249" target="_blank" class="tab-panel source-panel" data-tab="source-constraint-alphagenome-splice-site-usage">
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    <span class="source-path">evo-design/proto-language<span class="source-subpath">/proto\_language/constraint/rna\_splicing/alphagenome\_splice\_site\_usage.py</span></span>
  </div>

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  <div class="cite-code-wrap">
    ```bibtex theme={null}
    @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}
    }
    ```
  </div>

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<div class="entity-contributors"><span class="entity-contributors-label">Constraint contributors</span><span class="entity-contributors-people"><a class="entity-contributor" href="https://github.com/dguo8412" target="_blank" rel="noopener" title="dguo8412: 4 commits"><img noZoom class="entity-contributor-avatar" src="https://avatars.githubusercontent.com/u/46211285?v=4&s=64" alt="" loading="lazy" /><span class="entity-contributor-login">dguo8412</span></a><a class="entity-contributor" href="https://github.com/adititm" target="_blank" rel="noopener" title="adititm: 2 commits"><img noZoom class="entity-contributor-avatar" src="https://avatars.githubusercontent.com/u/61667248?v=4&s=64" alt="" loading="lazy" /><span class="entity-contributor-login">adititm</span></a></span></div>
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

<div class="api-model-section api-model-static api-config-section">
  <div class="api-model-header"><span class="api-model-badge api-config-badge">Config</span><span class="api-model-name">AlphaGenomeSpliceSiteUsageConfig</span><a href="https://github.com/evo-design/proto-language/blob/d3b7822f74ea64747cc751a3b2ab1aa6b799ac47/proto_language/constraint/rna_splicing/alphagenome_splice_site_usage.py#L134" target="_blank" class="func-table-btn func-source-btn api-model-source"><svg width="12" height="12" viewBox="0 0 24 24" fill="none" stroke="currentColor" stroke-width="2" stroke-linecap="round" stroke-linejoin="round"><polyline points="16 18 22 12 16 6" /><polyline points="8 6 2 12 8 18" /></svg> Source</a></div>

  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.

  <ParamField path="genomic_context" type="string" required>
    Genomic context sequence for cassette integration (e.g., AAVS1 safe harbor locus).
  </ParamField>

  <ParamField path="cassette_left_context" type="string" required>
    Left flanking context for the cassette (plasmid/gene sequence 5' of the target).
  </ParamField>

  <ParamField path="cassette_right_context" type="string" required>
    Right flanking context for the cassette (plasmid/gene sequence 3' of the target).
  </ParamField>

  <ParamField path="ontology_terms" type="List[string]" required>
    AlphaGenome ontology term(s) to score.
  </ParamField>

  <ParamField path="splice_pos" type="List[integer]" required>
    0-indexed position(s) in the concatenated target to evaluate.
  </ParamField>

  <ParamField path="direction" type="enum" default="max">
    'max' returns 1-mean(SSU); 'min' returns mean(SSU).

    Options: `max`, `min`
  </ParamField>

  <ParamField path="peak_search_radius" type="integer" default="0">
    Score each splice position as the max usage within +/- this many positions; 0 = exact index.
  </ParamField>

  <ParamField path="strand" type="enum" default="positive">
    Track strand subset to aggregate over.

    Options: `positive`, `negative`, `all`
  </ParamField>

  <ParamField path="model_version" type="string" default="all_folds">
    AlphaGenome model version.
  </ParamField>

  <ParamField path="organism" type="enum" default="human">
    Organism for AlphaGenome prediction.

    Options: `human`, `mouse`
  </ParamField>

  <ParamField path="device" type="string" default="cuda">
    Device for AlphaGenome prediction.
  </ParamField>

  <ParamField path="prediction_timeout" type="integer" default="3600">
    Timeout (seconds) for each AlphaGenome prediction call.
  </ParamField>
</div>

<div class="api-model-section api-model-static api-output-section">
  <div class="api-model-header"><span class="api-model-badge api-output-badge">Returns</span><span class="api-model-name">ConstraintOutput</span></div>

  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`.
</div>

## Usage

```python python icon="python" theme={null}
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`                           |
