Figure 1

Aggregating mutations using protein domains to form domain hotspots. (A) Mutations from multiple proteins in a single organism sharing a common protein domain mapped to the domain level. These mutations have different phenotypes but can be shown to form a large cluster at a single position in the domain, indicating similarity. (B) Mutations from multiple organisms mapped to a protein domain. These mutations form a large cluster of mutations at the domain level despite having originated from different species. (C) A domain hotspot is formed using mutations from only organism 1, but mutations aligning to the same domain position from organism 2 do not have enough mutations to form a domain hotspot. However, some association can still be drawn due to the existence of a domain hotspot in organism 1 aligning to a mutation in organism 2.