cfe-lab / cfe-lab/CFEIntact

Feature Request: Option to use a custom FASTA file as the alignment reference (e.g., for lab strains like NL4-3)

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enhancement
Dominant language
Python
Stars
5
Forks
4
Avg merge
10h 7m
Merged PRs (30d)
5

Description

Hi developers,

I am trying to use CFEIntact to QC a known, intact lab strain (NL4-3). However, because the tool forces an alignment against the default subtypes, it flags my input sequence as "Scrambled" due to minor coordinate differences between the two strains. Currently, there is no way to tell the tool that the input sequence is the "correct" reference.

I would like to request an option to provide a custom reference genome (e.g., --reference NL4-3.fasta). This would allow the tool to align the input sequence against a perfect match, thereby bypassing incorrect "scrambled" or "inversion" flags for known intact clones.

What I have tried:
I have already attempted using --ignore-scramble, which works but disables the scramble check entirely rather than resolving the underlying alignment issue.

Additional context:
The specific defect I am receiving is: Sequence is plus-scrambled. When I do a separate blast for my NL4-3 reference sequence to the default HXB2 reference that CFEIntact uses for subtype B, I see high identity (~96%), but the coordinate differences and gaps are causing the global alignment to fragment, triggering the false positive.

Why this matters:
If there were an option to provide a custom reference genome, it would be greatly useful for many HIV researchers who work with different engineered lab strains to check the intactness of their sequences. I would greatly appreciate if this can be achieved on your end, or if you can point me to any settings I can manually change to accommodate my needs.

Thank you for your consideration.

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First steps

  1. Read the whole issue, then the project's contributing guide.
  2. Comment on the issue to say you are picking it up — it saves two people doing the same work.
  3. Fork the repository and make your change on a branch.
  4. Open a pull request that references the issue number.

Research direction

Start by tracing the command-line handling for --ignore-scramble and the alignment against the default HXB2 reference. Define how a --reference FASTA option should select the alignment reference while preserving scramble and inversion checks, then verify behavior with an NL4-3 reference and input sequence; the issue names no source files or tests.

Written by the indexing model from the issue text.

Assessment

Tech stack
python
Domain
cli, data
Issue type
Feature
Difficulty
5/5
Estimated time
Over a week
Activity status
Quiet
Clarity
Mostly clear
Newbie friendliness
45/100

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