sokrypton / sokrypton/ColabFold

Local MSA results different from MSA server

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Description

Expected Behavior

I expect using colabfold_search with locally prepared DBs to give the same MSA results as those using colabfold_batch with the MSA server.

Current Behavior

The two give different MSA results given the same input .fasta.

Steps to Reproduce (for bugs)

  1. Install colabfold==1.5.5 via pip to a fresh new mamba environment (python==3.11.10).

  2. Build mmseqs2 of commit 71dd32ec43e3ac4dabf111bbc4b124f1c66a85f1 following ColabFold README.

  3. Execute the following to set up the DBs:

    MMSEQS_NO_INDEX=1 bash setup_databases.sh $colabfold_db_dir
    

    where I use the mmseqs2 built from step 2 for the tsv2exprofiledb commands.

  4. Prepare a sample .fasta file (say sample.fasta) of a single protein sequence.

  5. Get a locally generated MSA by:

    colabfold_search --mmseqs $mmseqs sample.fasta $colabfold_db_dir out_local
    # $mmseqs == mmseqs2 executable from step 2
    # Adding args `--db2 pdb100_230517` gave no change in the MSA outputs.
    
  6. Independently, get a MSA generated by querying the server like:

    colabfold_batch sample.fasta out_server --msa-only
    
  7. Compare the .a3m files generated from steps 5 and 6.

ColabFold Output (for bugs)

Omitted; I can attach outputs if necessary.

Context

I want to reproduce results from ColabFold notebooks on my local machine.

Your Environment

  • Git commit used: e2ca9e8f992cd65c986de5b64885d5572d8b8ad9
    where I used the ColabFold code only for executing setup_databases.sh. For colabfold_{search,batch} commands, I used v1.5.5 installed via pip.
  • Operating system and version: Red Hat Enterprise Linux 9.3 (Plow)

Contributor guide

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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 reproducing the comparison with colabfold_search and colabfold_batch using the sample.fasta and locally prepared databases from setup_databases.sh. Compare the generated .a3m files while checking the reported ColabFold and mmseqs2 versions; the issue is done when equivalent local and server runs produce matching MSA results or the discrepancy is explained.

Written by the indexing model from the issue text.

Assessment

Tech stack
python
Domain
bioinformatics
Issue type
Bug
Difficulty
4/5
Estimated time
3-5 days
Activity status
Stale
Clarity
Mostly clear
Newbie friendliness
35/100

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