Quantitative cross-species comparison of GO annotations: advantages and limitations of semantic similarity measure

We highlight the various kinds of difficulties arising when comparing two sets of GO annotations using either the intersection of sets of annotations or semantic similarity measures. We illustrate our approach by comparing the GO annotations of Apolipoprotein A-5 (apoa5) and Apolipoprotein A-1 (apoa1) respectively between human (hsa) and mice (mmu). Apoa5 is involved in similar biological processes in the two species [1], whereas Apoa1 is known to be significantly different [2]. For each gene product, we retrieved the annotations for each species using the GOA database from the EBI. We also retrieved the evidence codes and modifiers of these annotations in order to take negation into account [3, 4]. The Gene Ontology provided the hierarchy between the annotations. We used the daily version.