how should one treat samples in sequencing

Question

[Learner]

I have 2 control and 2 tumor samples which I have their exome sequencing data. I want to know if you should combine them after alignment during annotation or after annotation or when would be the best time to combine them ?

Or should I treat them separately ?

My other question is which database is best for mutation annotation?

[GenoMax]

Are the samples from different individuals or are they matched tumor/normals?

Rather than database you would want to use snpEff or VEP from Ensembl to do annotations.

[Learner]

@genomax Can you tell me what should I do in both cases? do you have any idea how to download those databases? is there any differences between all these annotation tools?