Help: Cannot load haploid VCF from snp-sites. Fails with "Must add at least one sample individual

[mandagaby18ag-design]

Hello tskit-dev team,

I am having extreme difficulty trying to infer an ARG from haploid virus data.

My pipeline is:

1. FASTA (84 sequences) -> mafft (alignment)
2. Alignment -> snp-sites -> VCF (this VCF has 1848 SNPs)
3. VCF -> tsinfer

The VCF from snp-sites seems incompatible with tsinfer. No matter what I try, I always get the error: Must add at least one sample individual (or Must add at least one site).

Here is what I have tried, and all of them fail with the same error:

• Using the old SampleData API (which shows a DeprecationWarning).
• Fixing the contig name (from '0' to '1', which is the contig in my VCF).
• Setting ploidy=1 in add_vcf.
• Adding individuals manually (samples.add_individual) before calling add_vcf.
• Adding individuals (samples.add_individual) and samples (samples.add_sample) before calling add_vcf.

I also wrote my own Python script to "clean" the VCF from snp-sites. My script successfully splits multi-allelic sites and creates a new, clean VCF with 2091 valid SNPs.

This is the main problem: Even when I try to load this "perfectly clean" VCF, tsinfer still fails with the exact same error: Must add at least one sample individual.

This makes me think the SampleData API is fundamentally broken for this task.

What is the correct, modern way (using SampleFile?) to load a haploid VCF (especially one from snp-sites)? All my attempts have failed.

Thank you for any help you can provide.
(My environment: Linux, Python 3.11, tsinfer version 0.4.1)

[hyanwong]

The "Modern" way is to convert the VCF to VCF-Zarr format, see e.g. https://sgkit-dev.github.io/bio2zarr/vcf2zarr/overview.html. Could you try this and let us know if you successfully create a .vcz file?

Once you have it in .vcz, you should be able to follow the steps at https://tskit.dev/tsinfer/docs/stable/usage.html#variantdata-and-ancestral-alleles without any problems, I hope.

If you have a small example VCF you are having problems with (e.g. < 5MB), you cold post it here?