Implement DNA-to-Protein Pipeline (Work Order 03) by AkeBoss-tech · Pull Request #7 · AkeBoss-tech/HiC-TAD-Library

AkeBoss-tech · 2026-04-05T04:58:08Z

This submission addresses Work Order 03: The DNA-to-Protein Pipeline. It implements transcription, alternative splicing simulation, rule-based translation, and protein structure impact analysis (mock API). Tested for frameshift deletions and pLDDT drop (structural collapse) edge cases. Tests passing correctly.

PR created automatically by Jules for task 13697527110041319258 started by @AkeBoss-tech

- Added `predict_isoforms` to assemble mature mRNA from reference and mutant sequences. - Added `translate` and `compare_translation` for codon-to-AA translation and frameshift detection. - Added `ProteinFolder` API wrapper to predict protein structure mock pLDDT scores. - Implemented `compute_structure_impact` to assess structural collapse. - Added tests to verify frameshifts and structural collapse detection. Co-authored-by: AkeBoss-tech <69588353+AkeBoss-tech@users.noreply.github.com>

google-labs-jules · 2026-04-05T04:58:09Z

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Pull request overview

Implements a basic DNA→mRNA→protein pipeline under src/hg_dt/, plus tests covering a frameshift deletion and a mocked “structural collapse” signal using pLDDT deltas.

Changes:

Add transcript isoform assembly from exon annotations and edited sequence windows.
Add ORF detection + translation and a simple translation comparison (frameshift heuristic).
Add a mock protein folding wrapper and a pLDDT-based structural impact metric, with tests for key edge cases.

Reviewed changes

Copilot reviewed 6 out of 6 changed files in this pull request and generated 8 comments.

Show a summary per file

File	Description
`src/hg_dt/translate/transcript.py`	Builds ref/mut mRNA sequences per transcript by concatenating exon segments and handling strand/RNA conversion.
`src/hg_dt/translate/translator.py`	Finds longest ORF and translates to AA; compares ref vs mut translation for frameshift/truncation detection.
`src/hg_dt/models/protein.py`	Introduces a mocked protein folding API wrapper that returns synthetic pLDDT scores.
`src/hg_dt/analyze/deltas.py`	Adds `compute_structure_impact` to summarize pLDDT deltas and flag potential fold collapse.
`tests/hg_dt/test_pipeline.py`	Adds unit tests for frameshift deletion translation and structural collapse/no-collapse scenarios.
`pip_install.sh`	Adds a pip install step for `pyranges`.

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Copilot · 2026-04-05T05:01:34Z

+def compare_translation(ref_mrna: str, mut_mrna: str) -> Dict[str, any]:
+    """


compare_translation is annotated as Dict[str, any], but any is the built-in function, not a typing type. Use typing.Any (and import it) or a more precise TypedDict/return dataclass so type checkers don’t misinterpret this annotation.

Copilot · 2026-04-05T05:01:34Z

+def compute_structure_impact(ref_plddt: List[float], mut_plddt: List[float]) -> Dict[str, float]:
+    """
+    Computes structural impact metrics between reference and mutant pLDDT scores.


compute_structure_impact is annotated as returning Dict[str, float], but the returned dict includes a boolean (collapse). Adjust the return type (e.g., Dict[str, Any] or a TypedDict) to match the actual values.

Copilot · 2026-04-05T05:01:35Z

+        Dictionary of metrics, including average pLDDT drop and whether structural collapse occurred.
+    """
+    if not ref_plddt and not mut_plddt:
+        return {'avg_drop': 0.0, 'collapse': False}


When both inputs are empty, this function returns only avg_drop and collapse, but in the non-empty case it returns additional keys (avg_ref_plddt, avg_mut_plddt). Returning inconsistent shapes makes the API harder to consume; consider always returning the full key set (with 0.0 defaults) even in the empty-input case.

Suggested change

return {'avg_drop': 0.0, 'collapse': False}

return {

'avg_ref_plddt': 0.0,

'avg_mut_plddt': 0.0,

'avg_drop': 0.0,

'collapse': False

}

Copilot · 2026-04-05T05:01:35Z

+import os
+import requests
+from typing import Dict, Optional, Tuple, List
+
+class ProteinFolder:
+    """Wrapper for a protein folding API (e.g. BioNeMo AlphaFold/ESMFold)."""
+
+    def __init__(self, api_key: Optional[str] = None):
+        # We simulate the API call. In a real environment, we'd use BioNeMo's REST API.
+        self.api_key = api_key or os.environ.get("BIONEMO_API_KEY", "mock_key")


requests, Tuple, and List are imported but unused in this module. If the folding API call is intentionally mocked for now, consider removing unused imports (and potentially the unused api_key field) to avoid implying external network behavior and to keep the module’s dependency surface minimal.

Suggested change

import os

import requests

from typing import Dict, Optional, Tuple, List

class ProteinFolder:

"""Wrapper for a protein folding API (e.g. BioNeMo AlphaFold/ESMFold)."""

def __init__(self, api_key: Optional[str] = None):

# We simulate the API call. In a real environment, we'd use BioNeMo's REST API.

self.api_key = api_key or os.environ.get("BIONEMO_API_KEY", "mock_key")

from typing import Dict

class ProteinFolder:

"""Wrapper for a protein folding API (e.g. BioNeMo AlphaFold/ESMFold)."""

def __init__(self):

# We simulate the API call. In a real environment, we'd use BioNeMo's REST API.

pass

Copilot · 2026-04-05T05:01:35Z

+    def predict_structure(self, aa_seq: str) -> Dict[str, any]:
+        """


predict_structure is annotated as returning Dict[str, any], but any is the built-in function, not a typing type. Use typing.Any (or a TypedDict) for correct type annotations.

Copilot · 2026-04-05T05:01:35Z

@@ -0,0 +1 @@
+pip install pyranges


This install script adds pyranges, but the new pipeline code imports Biopython (Bio.Seq) and the mock folding wrapper imports requests. Neither biopython nor requests appear in environment.yml, so a fresh environment following repo setup will likely fail at import time. Consider adding the missing deps either here (pip) or to environment.yml so CI/users get a reproducible install.

Suggested change

pip install pyranges

pip install pyranges biopython requests

Copilot · 2026-04-05T05:01:36Z

+import pytest
+import pandas as pd
+from src.hg_dt.translate.transcript import predict_isoforms
+from src.hg_dt.translate.translator import compare_translation, translate


pytest and translate are imported but not used in this test module. Removing unused imports will keep the tests clean and avoid misleading readers about what’s being exercised.

Suggested change

import pytest

import pandas as pd

from src.hg_dt.translate.transcript import predict_isoforms

from src.hg_dt.translate.translator import compare_translation, translate

import pandas as pd

from src.hg_dt.translate.transcript import predict_isoforms

from src.hg_dt.translate.translator import compare_translation

Copilot · 2026-04-05T05:01:36Z

+    # 1 bp deletion at position 4 (G -> deleted)
+    # Ref: ATG GCC ATT GTA ATG GGC CGC TGA (start -> GCC -> ATT -> GTA -> ATG -> GGC -> CGC -> TGA stop)
+    # Ref AA: M A I V M G R *
+
+    # Mut: ATG CCA TTG TAA (start -> CCA -> TTG -> TAA stop)
+    # Mut AA: M P L *


The comment says “1 bp deletion at position 4” but the test parameters use edit_start=3, edit_end=4 (0-based half-open semantics). Consider clarifying the coordinate convention in the comment (0-based vs 1-based) to prevent future confusion when modifying this test.

Copilot AI review requested due to automatic review settings April 5, 2026 04:58

Copilot started reviewing on behalf of AkeBoss-tech April 5, 2026 04:58 View session

Copilot AI reviewed Apr 5, 2026

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Implement DNA-to-Protein Pipeline (Work Order 03)#7

Implement DNA-to-Protein Pipeline (Work Order 03)#7
AkeBoss-tech wants to merge 1 commit intoalphagenome-integration-3754893517514412865from
feat/dna-to-protein-pipeline-13697527110041319258

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		def compare_translation(ref_mrna: str, mut_mrna: str) -> Dict[str, any]:
		"""

		def predict_structure(self, aa_seq: str) -> Dict[str, any]:
		"""

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