Should --very-sensitive be combined with -no-1mm-upfront?

Question

[Lucy]

Hi,

I am planning to use the --very-sensitive option for aligning my ATAC-seq reads. However, after reading the manual section below, I am unclear as to whether this option should be combined with --no-1mm-upfront or not?

"By default, Bowtie 2 will attempt to find either an exact or a 1-mismatch end-to-end alignment for the read before trying the multiseed heuristic. Such alignments can be found very quickly, and many short read alignments have exact or near-exact end-to-end alignments. However, this can lead to unexpected alignments when the user also sets options governing the multiseed heuristic, like -L and -N."

Many thanks,

Lucy

Answer 1

[Devon Ryan]

--very-sensitive doesn't change the permitted number of mismatches to 0, so you don't need to specify --no-1mm-upfront.