This is a test version of Biostars. For the public version, visit https://www.biostars.org.
Which Aligners Recognize Soft-Masked Repeats In Reference Sequences?

Which aligners (long and short read) behave differently when parts of a reference/target sequence are "soft-masked", i.e. have portions in lowercase to designate repeat regions?

alignment
• 13,866 views • link
updated by Ali R. Vahdati Ali R. Vahdati • written by Jeremy Leipzig Jeremy Leipzig

3 answers

No, do not align to masked genome for any purpose. Filter out the reads mapped to the masked region after whole-genome alignment.

• 1 views • link
written by lh3 lh3

What will be a difference, except for paired-ends or spliced mappings?

• 0 views • link
written by Darked89 Darked89

so I assume BWA does not care about lowercase nucleotides?

• 0 views • link
written by Jeremy Leipzig Jeremy Leipzig

Masking has never been perfect and probably will never be perfect. This will lead to wrongly mapped sequences, spurious SNPs/indels calls and all sorts of problems. I cannot think a single use case when masking may lead to better outcomes. Trust me. Do not mask.

• 0 views • link
written by lh3 lh3

BWA always uses all bases in alignment. Again, do not mask, unless you want to play with troubles.

• 0 views • link
written by lh3 lh3

Yup. Do not mask. You get the most accurate alignment when you align to what is actually there. What you do not want are reads that really belong to repetitive regions being forced to align to the wrong place because you didn't provide the correct sequence for the read to align to.

bwa does not care about lowercase nucleotides.

• 0 views • link
written by swbarnes2 swbarnes2

LASTZ, 'soft-masked' regions are NOT available for seeding but allow extension. It also allows you to specify a separate file for the intervals to mask (with softmask=<mask_file>).

• 1 views • link
written by Haibao Tang Haibao Tang

FSA also takes into account soft-masked regions when supplied with --softmasked option.

• 0 views • link
updated by Ram Ram • written by Ali R. Vahdati Ali R. Vahdati

Log in to answer this question.

More posts like this