1. If you are interested in coding variants, you could consider supplying a set of regions to samtools to limit calling to those regions.
2. Consider running several samples in parallel since samtools is single-threaded.

I've also noticed that samtools' default performance is quite slow. Until the recent development work on samtools catches up and provides suitable defaults, I suggest using freebayes. /shameless plug/

You can call somatic variants in a tumor/normal pair as such:

freebayes -f ref.fa --pooled-discrete --genotype-qualities tumor.bam normal.bam | vcfsamplediff -s VT normal tumor -

In my experience, getting good results this way has required post-filtering (using vcfsom specifically). I'm still waiting on results from the most-recent TCGA variant calling exercise. Please write the freebayes mailing list if you have any questions.

Oh, and you'll want to add read groups to the files so that you can call them all at the same time. This is easily done with bamaddrg.

Hi Erik, I used the command you suggested above to call somatic variants in tumor-normal pairs, and the resulting VCF file named, 'freebayes_pooled-discrete.vcf' had

##INFO=<ID=SSC,Number=1,Type=Float,Description="Somatic variant score (phred-scaled probability that the somatic variant call is correct).">

However, looking at some of the data lines and using 'grep SSC freebayes_pooled-discrete.vcf', none of the called variants had the Somatic variant score (SSC). Could you be knowing why this is so? The exact command line I used was:

freebayes  --no-indels --no-mnps --no-complex -f hg19.fa --pooled-discrete --genotype-qualities normal.bam tumor.bam | ./vcfsamplediff -s VT normal.bam tumor.bam - | ./vcffilter  -f "QUAL > 20" > freebayes_pooled-discrete.vcf

Also, I am using muTect and it has PASS and SOMATIC defined as:

##FILTER=<ID=PASS,Description="Accept as a confident somatic mutation"> 
##INFO=<ID=SOMATIC,Number=0,Type=Flag,Description="Somatic event">

How do these compare with freebayes as I used it? I am trying to determine which parameters will best make freebayes and muTect comparable when it comes to calling somatic point mutations. The muTect command I used is:

java -Xmx2g -jar muTect-1.1.4.jar --analysis_type MuTect --reference_sequence hg19.fa --dbsnp dbsnp_137.hg19.vcf --input_file:normal normal.bam --input_file:tumor tumor.bam --out mutect_results.txt --coverage_file mutect_coverage.wig --enable_extended_output  --vcf mutect_results_extended.vcf

Would really appreciate your advice!