TreeGrafter: phylogenetic tree-based annotation of proteins with Gene Ontology terms and other annotations

Abstract

Summary: TreeGrafter is a new software tool for annotating protein sequences using pre-annotated phylogenetic trees. Currently, the tool provides annotations to Gene Ontology (GO) terms, and PANTHER family and subfamily. The approach is generalizable to any annotations that have been made to internal nodes of a reference phylogenetic tree. TreeGrafter takes each input query protein sequence, finds the best matching homologous family in a library of pre-calculated, pre-annotated gene trees, and then grafts it to the best location in the tree. It then annotates the sequence by propagating annotations from ancestral nodes in the reference tree. We show that TreeGrafter outperforms subfamily HMM scoring for correctly assigning subfamily membership, and that it produces highly specific annotations of GO terms based on annotated reference phylogenetic trees. This method will be further integrated into InterProScan, enabling an even broader user community.

Availability and implementation: TreeGrafter is freely available on the web at https://github.com/pantherdb/TreeGrafter, including as a Docker image.

Supplementary information: Supplementary data are available at Bioinformatics online.

Fig. 1.

TreeGrafter annotates each sequence based on where it is grafted onto an annotated reference tree. Given the same tree with pre-annotated ancestral gene nodes (left panel), each query sequence is grafted onto the tree. For the graft position of query 1 (top, blue open circle) there are two annotated ancestral nodes from which query 1 inherits annotations, while for query 2 (bottom, blue open circle), there is only one annotated ancestral node and only the annotations from this one node are inherited by query 2