Overview of the Exogean methodology. Exogean annotations are based on protein and/or mRNA alignments. Protein sequences come from a different species than that of the DNA to be annotated (for example, mouse protein to annotate human genes), while the mRNAs originate from tissues of the species being annotated. (a) These alignments are first processed to remove artifacts using heuristics. (b) The core of the method is the directed acyclic multigraph (DACM) component, which builds transcripts of increasing complexity in three iterative steps using a second set of heuristics. (c) The transcripts are then examined to identify a complete or a partial coding sequence (CDS), and (d) a last filter applies a last set of rules to remove pseudogenes.