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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

ProtoNet 6.0 (http://www.protonet.cs.huji.ac.il) 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 languageAmerican English
Pages (from-to)D313-D320
JournalNucleic Acids Research
Volume40
Issue numberD1
DOIs
StatePublished - Jan 2012

Bibliographical note

Funding Information:
Sudarsky Center for Computational Biology (SCCB) fellowship (to N.R.); EU FRVII Prospects consortium and the Israel Science Foundation ISF 592/07. Funding for open access charge: EU FRVII Prospects consortium and the Israel Science Foundation ISF 592/07.

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