A Roadmap to Domain Based Proteomics.

Protein domains are reusable segments of proteins and play an important role in protein evolution. By combining the elements from a relatively small set of domains into unique arrangements, a large number of distinct proteins can be generated. Since domains often have specific functions, changes in their arrangement usually affect the overall protein function. Furthermore, domains are well amenable to computational representations, e.g., by Hidden Markov Models (HMMs), and these HMMs are widely represented in various databases. Therefore, domains can be efficiently used for proteomic analyses. Here, we describe how domains are annotated using different domain databases and then how to assess the annotation quality of proteomes. We next show how functional annotations of domains in large-scale data such as whole genomes or transcriptomes can be used to analyze molecular differences between species. Furthermore, we describe methods to analyze the changes in domain content of proteins which significantly helps to characterize and reconstruct the modular evolution of proteins. Altogether, domain-based methods offer a computationally highly effective approach to analyze large amounts of proteomic data in an evolutionary setting.