I am performing copy number analysis on some exome sequencing data where some of the samples does not have the matched normal (the tool that I am using - ADTEx - requires a matched normal sample for the copy number analysis). However, I have 3 normal samples (bam files) which are prepared and sequenced the same way as the tumor samples (those that do not have the normal samples). I was wondering what the best practices are in order to create a pooled normal exome sample?
Currently, I am thinking of merging 3 normal bam files using 'samtools merge' and then find the coverage for each exon using 'coverageBed' and then divide the coverage for each exon by 3. However, I am not sure if this way is correct and whether I need to do some kind of normalization. In addition, I have noticed that 'ExomeCNV' R package has a function called 'pool.coverage()' which is meant for this purpose but unfortunately this package has been removed from CRAN!
I would like to thank you in advance for your thoughts and answers.