Handling of loci with interruptions and complex motifs

[HLHsieh]

Hi Fang,

I have a few questions regarding the handling of loci with interruptions and complex motifs in NanoRepeat.

I saw that NanoRepeat supports joint quantification of two adjacent STRs. However, I’m wondering whether this approach can also be applied when two different motifs occur within the same locus, rather than in adjacent regions. For example, would a command like the following work?

nanoRepeat-joint.py -i sample.fastq -r ref.fasta -1 chr4:3074876:3074933:CAG:200  -2 chr4:3074876:3074933:CAA:20 -o test

Alternatively, would it be more appropriate to use nanoRepeat.py directly with a BED file like:

4 3074876 3074933 CAG  
4 3074876 3074933 CAA

Similarly, would this approach work for interrupted repeats? Specifically, is it possible to identify and count the number of interruption motifs (e.g., interruptions within a CAG array)?

Lastly, how does NanoRepeat currently handle mosaic repeat expansions? Are there features or parameters that help detect or quantify mosaicism in the current implementation?

I believe I can tune the --max_num_components or --remove_noisy_reads parameters to achieve this goal. Am I right? However, what is the difference between these two parameters?

Any clarification or recommendations would be greatly appreciated.

Best regards,
Hsin