Phylogenetic annotation overview

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Principles underlying PAINT

Annotation of a gene's function by homology is often referred to as "transitive annotation", in which an experimentally-characterized function of one gene is "transferred" to another gene because of their similarity in sequence. This pairwise transfer paradigm derives from the success of sequence searching algorithms such as BLAST and Smith-Waterman. Of course, pairwise conservation of function is really due to descent from a common ancestor (homology). In other words, two sequences of sufficient length are similar because they share a common ancestor, and the reason they have a common function is most likely that they inherited that function from their common ancestor. This process can be explicitly captured using a phylogenetic model.

Rather than a pairwise paradigm, PAINT uses this more accurate phylogenetic model to infer gene function by homology. PAINT (Phylogenetic Annotation and INference Tool) annotation is intended to capture actual inferences about the evolution of gene function within a gene family: the gain, inheritance, modification and loss of function over evolutionary time. Inference is a two-step process, and involves directly annotating a phylogenetic tree. In the first step, experimental GO annotations for extant sequences are used to make inferences about when a given function may have first evolved. In PAINT, this is referred to as "up-propagation", in which ancestral genes are annotated based on information about extant sequences. In the second step, "down-propagation", ancestral annotations are used to make inferences about unannotated extant sequences, based on the principle of inheritance from the common ancestor, and allowing for modification and even loss of function during evolution.

For a more complete description, please see the publication on the GO Phylogenetic Annotation process, Gaudet et al, Briefings in Bioinformatics, 2011.

PAINT software

PAINT is implemented in Java, as a joint project between Paul Thomas's group (USC) and Suzanna Lewis's group (LBL). Development of PAINT has been funded by grant GM081084 from the U.S. National Institutes of Health, and the GO Consortium grant 5U41HG002273.


PAINT is freely available for download from the Panther website:

Installing and using PAINT

See the PAINT User Guide for more information.

Standard operating procedures for GO annotation using PAINT

The GO Reference Genome Project is annotating trees generated for PANTHER version 15, released on 2020-02-14.

Annotation of GO terms using PAINT follows the (see the PAINT SOP).

Review Status

Last reviewed: November 11, 2020