Which aligner is more suitable for ONT R10.4.1 Dorado-corrected reads: minimap2 or winnowmap?

Question

[tungsega]

Hello everyone,

I currently have ONT R10.4.1 simplex reads corrected by Dorado, and I am considering which aligner would be more suitable — minimap2 or winnowmap.

I plan to perform the following analyses after mapping:

1. ONT Read phasing, using an existing VCF generated from short reads (from the same sample) and the hg38 reference.
2. Assembly polishing.
3. Structural variant calling.

I know that minimap2 already provides the lr:hq and lr:hqae presets specifically designed for ONT R10.4.1 data. On the other hand, winnowmap currently seems to lack equivalent parameters to reproduce the lr:hq preset environment (issue for lr:hq preset discussion).

However, I’m not sure whether minimap2’s latest version has improved performance in repetitive regions compared to previous releases.

I’d really appreciate hearing others’ experiences or opinions: Which aligner would you recommend for ONT R10.4.1 Dorado-corrected reads, especially for downstream phasing and SV detection?

Thank you very much for your time and suggestions!

Best Regards

[colindaven]

Good summary. I never tried winnowmap despite it's apparent advantages. If you have really repeat rich regions like centromeres that it may be useful. However my gut feeling is that ONT sequencing has moved on again considerably in the last 2 years so the error model of Winnowmap might not be appropriate any more. Perhaps ask the authors ? Certainly, the more modern minimap presets would appear to be beneficial for dealing with the latest ONT data.
If this is just one alignment though, then why not do both and let the community know about your experiences ?

[tungsega]

Thank you for your reply.

I’m currently trying to perform alignments using both aligners, but I wanted to ask if anyone has conducted a similar systematic comparison before.

Actually, I’m not quite sure about the best way to evaluate the performance differences between aligners. I was thinking of comparing metrics such as the NM tag, samtools flagstat, or MAPQ values.

Could you please give me some advice or suggestions on how to properly compare the results?

Answer 1

[okiedokie1208]

I believe ONT recommends Minimap2. This is also the default tools in their EPI2ME workflow.