samtools mpileup command has quite a neat feature that it is able to correct mapping errors associated with misalignment of INDELs. By default, the
mpileup command will not work for reads that have more than 250X coverage of the reference genome. While this limit can be increased, very high coverage causes the mpileup program to grind to a halt, so it'd be nice to know if there's some easy way to make that faster.
To add a bit more context, I've been doing this with mitochondrial genome reads that were extracted from both Illumina whole-genome sequencing (coverage ~1000X), and from targeted amplicon sequencing done on the IonTorrent (coverage up to ~4000X).
I see that @rightskewed has mentioned the downsampling ability of samtools with
samtools view -s <float> (see here), which seems like it might work as a solution for this if used prior to the mpileup operation.