What is genome annotation?
Before addressing the problems with annotation, I will first summarize how it is done. The process of sequencing and annotating the DNA of a bacterial species has become highly automated in recent years, but the major steps are quite similar to what was done for the very first bacterial genome, Haemophilus influenzae, in 1995 [5]. Figure 1 shows an outline of the main steps of the whole-genome shotgun sequencing and annotation process for a bacterial genome. Similar procedures – for both sequencing and annotation – are followed for much larger genomes, including the human genome, although the details vary. The laboratory steps have not changed greatly since H. influenzae: they begin with DNA purification, followed by shearing the DNA into countless small fragments (the ‘shotgun’ step). These fragments are then cloned and sequenced from both ends and assembled, usually resulting in a set of contiguous DNA sequences (contigs) joined together into larger scaffolds. The annotation pipeline
