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I'm faced with having to align many (some 100s) bacterial genomes, where the genome length is in the millions. Obviously, this is beyond normal alignment techniques and it's unclear to me what the best practice is for such circumstances:

  • conventional alignment on a very powerful computer with lots of memory
  • break up the genome into smaller fragments and align them individually
  • some exotic different procedure

What possible avenues of attack are there?

(I've attempted to use Mafft and Clustal with little success)

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    $\begingroup$ A standard MSA tool like Clustal will assume that there are no rearrangements between sequences. Unless all of your sequences are completely colinear, you'll need a dedicated genome alignment method like MUMmer. $\endgroup$
    – heathobrien
    Commented Jun 14, 2017 at 14:29
  • $\begingroup$ Adding some clarifications: there are no large scale rearrangements (otherwise I wouldn't try this). Most solutions are pairwise or to a reference, which isn't what I want to do here. $\endgroup$
    – agapow
    Commented Jun 14, 2017 at 14:34
  • $\begingroup$ I wouldn't expect Clustal to work but what went wrong with MAFFT? I'm pretty sure that's been used for whole genome alignments on vertebrate data, so I would be surprised if it failed for bacteria. $\endgroup$
    – terdon ♦
    Commented Jun 14, 2017 at 14:36
  • $\begingroup$ There are some tips here to run mafft on a relatively small number of long sequences. $\endgroup$
    – heathobrien
    Commented Jun 14, 2017 at 14:40
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    $\begingroup$ Have you considered using LASTZ (bx.psu.edu/~rsharris/lastz )? It is meant to align chromosome sized entities? $\endgroup$
    – GenoMax
    Commented Jun 14, 2017 at 23:48

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Whole genome aliment can be done using Progressive Mauve, LAST or Mummer. For bacteria I used Mauve since it has also very nice visualisation engine. A very new tool is Minimap2, a super fast mapper that supposed beside read mapping be able to handle reference vs reference. However, I do not know how performance of it compares to the tools mentioned above.

If you are interested in a rough idea of the shared genome regions, you can use bevel. Bevel is not really an aligner, it is more like a dot-plot, but it is super fast (even for mammalian sized genomes).

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