ProtoNet 6.0: Organizing 10 million protein sequences in a compact hierarchical family tree

Nadav Rappoport, Solange Karsenty, Amos Stern, Nathan Linial, Michal Linial

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


ProtoNet 6.0 ( is a data structure of protein families that cover the protein sequence space. These families are generated through an unsupervised bottom-up clustering algorithm. This algorithm organizes large sets of proteins in a hierarchical tree that yields high-quality protein families. The 2012 ProtoNet (Version 6.0) tree includes over 9 million proteins of which 5.5% come from UniProtKB/ SwissProt and the rest from UniProtKB/TrEMBL. The hierarchical tree structure is based on an all-against-all comparison of 2.5 million representatives of UniRef50. Rigorous annotation-based quality tests prune the tree to most informative 162 088 clusters. Every high-quality cluster is assigned a ProtoName that reflects the most significant annotations of its proteins. These annotations are dominated by GO terms, UniProt/Swiss-Prot keywords and InterPro. ProtoNet 6.0 operates in a default mode. When used in the advanced mode, this data structure offers the user a view of the family tree at any desired level of resolution. Systematic comparisons with previous versions of ProtoNet are carried out. They show how our view of protein families evolves, as larger parts of the sequence space become known. ProtoNet 6.0 provides numerous tools to navigate the hierarchy of clusters.

Original languageEnglish
Pages (from-to)D313-D320
JournalNucleic Acids Research
Issue numberD1
StatePublished - 1 Jan 2012
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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