problems in hg19 and b37 compatibility

Question

[Nicola Casiraghi]

Hi everybody,

A bam file has been aligned using hg19 reference genome. Thus, the chromosome notation is [chrM, chr1, chr2, chr3, chr4, ..., chrX,chrY].

I want to look for PMs using MuTect that requires in input vcf files from dbSNP and COSMIC. In these vcf files the chromosome notation is [1,2,3,4,...,MT,X,Y] according to b37 notation.

a) As expected running MuTect on these files, it returns the error:

##### ERROR MESSAGE: Input files dbsnp and reference have incompatible contigs: No overlapping contigs found.

b) I succesfully reheader bam file in order to remove 'chr' and changing chrM to MT, but the error now is:

##### ERROR MESSAGE: Input files reads and reference have incompatible contigs: Found contigs with the same name but different lengths:
##### ERROR   contig reads = MT / 16571
##### ERROR   contig reference = MT / 16569.

c) The last attempt was to add 'chr' and replace chrM to dbSNP and COSMIC vcf files required by MuTect. Error is:

##### ERROR MESSAGE: Invalid command line: No tribble type was provided on the command line and the type of the file could not be determined dynamically.

How can I run MuTect on these bam and vcf files?

many thanks

[Devon Ryan]

Allegedly there's an hg19 to b37 liftOver file provided by GATK in the resource bundle. If nothing else, just use that and call it done (I imagine that'll take a while to run).

[Chris Fields]

Devon, you should put this as the answer so Nicolas can accept it.

Answer 1

[Chris Fields]

The two build are very similar but not exactly the same; IIRC this is a known problem with hg19/b37 (note the difference in chrM size mentioned in the error message). See these links:

• http://seqanswers.com/forums/archive/index.php/t-18377.html
• http://gatkforums.broadinstitute.org/discussion/1810/what-s-the-difference-between-b37-and-hg19-resources

Note that the second link mentions the liftover data needed for a hg19->b37 conversion, as @Devon pointed out.

Answer 2

[Nicola Casiraghi]

Hi everybody, many thanks for all your helps and suggestions.

@Devon, I found in ftp://[e-mail]/Liftover_Chain_Files and here files that should be able to convert b37toh19 and viceversa. Unfortunately, and I do not know why, it doesn't work in my case. I'm working on it to fix the problem.

@Chris, thank you for the links, the first one is exactly my problem.

[Devon Ryan]

When you say that it doesn't work what exactly do you mean? Do you get an error message? If so, what is it?

[rse]

Were you able to solve the problem?

[Chris Fields]

We ran into this issue a few years ago, and the quickest way we found to solve it was to rerun the analysis with the 'correct' chrM, as suggested in the second link.

[Manuel Sokolov Ravasqueira]

The link does not work, is there any way to find the Liftover_Chain_Files to convert b37 into hg19?

Answer 3

[chan-song]

You may use the following steps:

1. Convert the b37 chromosome notation in those vcf files into the hg19 chromosome notation
2. Use igvtools (http://www.broadinstitute.org/software/igv/download) to re-create index files for those vcf files