Circular Genome Alignment

Question

[isaac.rstefan]

Hello all,

I'm aligning sequencing data to the human mitochondrial genome with Bowtie2. To handle the fact that the genome is circular, I'm doing two alignments (in which one has a shifted origin) as aligners treat the genome as linear. My goal was to replace the reads from one to the other where the origin is. However, when I do this, regions that should have the same number of reads in each alignment are significantly different. Further, the total number of reads that align is also VERY different. Does anyone have any suggestions on what might be going wrong or what to do?

Best, Stefan

[h.mon]

A common technique is adding a bit of "over-hangs" from the other side of the break at the extremes of the linearized circular contig - this would allow the reads to map at the extremities, and is simpler than the approach you are taking.

[Buffo]

bwa has the option to apply soft and hard clipping, it may be usefull, or hisat2 by default performs spliced alignments.

Answer 1

[Jonathanjacobs]

FWIW - CLC Genomics Workbench's read mapper supports circularized reference genomes and will map reads across origins without any issue.