Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium

By Pascale Gaudet, M. Livstone, Suzanna Lewis, Paul D. Thomas. Briefings Bioinform., 2011

783 citations recorded by the source corpus.

The goal of the Gene Ontology (GO) project is to provide a uniform way to describe the functions of gene products from organisms across all kingdoms of life and thereby enable analysis of genomic data. Protein annotations are either based on experiments or predicted from protein sequences. Since most sequences have not been experimentally characterized, most available annotations need to be based on predictions. To make as accurate inferences as possible, the GO Consortium's Reference Genome Project is using an explicit evolutionary framework to infer annotations of proteins from a broad set of genomes from experimental annotations in a semi-automated manner. Most components in the pipeline, such as selection of sequences, building multiple sequence alignments and phylogenetic trees, retrieving experimental annotations and depositing inferred annotations, are fully automated. However, the most crucial step in our pipeline relies on software-assisted curation by an expert biologist. This curation tool, Phylogenetic Annotation and INference Tool (PAINT) helps curators to infer annotations among members of a protein family. PAINT allows curators to make precise assertions as to when functions were gained and lost during evolution and record the evidence (e.g. experimentally supported GO annotations and phylogenetic information including orthology) for those assertions. In this article, we describe how we use PAINT to infer protein function in a phylogenetic context with emphasis on its strengths, limitations and guidelines. We also discuss specific examples showing how PAINT annotations compare with those generated by other highly used homology-based methods.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/53224f21b51a1e2870f4f4bd35870c4111fc1e0d

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Citations in the corpus

Saccharomyces Genome Database: the genomics resource of budding yeast (2011, background): “Researchers often transfer GO functional annotations between homologous proteins, thus the accuracy of SGD’s literature annotations is of utmost importance (9,10).”
PANTHER version 10: expanded protein families and functions, and analysis tools (2015, methodology): “These updated annotations are taken from the Gene Ontology Phylogenetic Annotation Project, described in Gaudet et al. (4).”
The Gene Ontology of eukaryotic cilia and flagella (2017, methodology): “Abbreviations BP: biological process; CC: cellular component; EMBL-EBI: European Molecular Biology Laboratory, European Bioinformatics Institute; GO: Gene Ontology; GOC: Gene Ontology Consortium; MF: molecular function; OBO: open biomedical ontologies; PAINT: Phylogenetic Annotation and INference To”
DeepGO: predicting protein functions from sequence and interactions using a deep ontology-aware classifier (2017, methodology): “Function prediction can use several sources of information, including protein-protein interactions [24], genetic interactions [12], evolutionary relations [14], protein structures and structure prediction methods [19], literature [28], or combinations of these [25].”
The Gene Ontology: enhancements for 2011 (2011, methodology): “The reference genome annotation project has been greatly enhanced by the use of the PAINT tool to infer functional information across closely related genes in a wide variety of organisms (3).”
Updates in Rhea – an expert curated resource of biochemical reactions (2016, methodology): “It can be used to annotate extant members of this orthologous group as well as ancestral functions in phylogenetic trees (20) at a greater level of precision than the generic ‘aldehyde lyase’ annotation EC 4.”
PANTHER version 16: a revised family classification, tree-based classification tool, enhancer regions and extensive API (2020, methodology): “Annotations for a new sequence depend on the graft point on the reference tree, and include PANTHER subfamily, and manually-annotated GO terms on tree branches made by the Gene Ontology Phylogenetic Annotation project (12) (Figure 5B).”
Large-scale gene function analysis with PANTHER Classification System (2013, methodology): “The phylogenetic-inferred curation paradigm has become part of the GO curation pipeline, and therefore PANTHER annotation reflects a more up-to-date GO curation 22 .”
PANTHER: Making genome‐scale phylogenetics accessible to all (2021, methodology): “PANTHER trees are manually annotated, by curators from the GO Phylogenetic Annotation project, 24 with The Protein Analysis THrough Evolutionary Relationships (PANTHER) pipeline transforms raw protein sequence data into knowledge about gene family and function evolution.”
Primer on the Gene Ontology (2016, methodology): “When this code is assigned by PAINT, GO’s Phylogenetic Annotation and INference Tool (31), this means that it is a prediction based on evolutionary neighbors.”
FFPred 3: feature-based function prediction for all Gene Ontology domains (2016, methodology): “The GO consortium, for instance, makes wide use of a semi-automated tool for phylogenetic analysis and functional inference 2 , and of mappings between protein domain families to GO terms that are valid for all their members 3 .”
InterPro: the protein sequence classification resource in 2025 (2024, positive): “These GO annotations are obtained from manually curated, explicit models of function evolution in protein families, from the Phylogenetic Annotation using Gene Ontology (PAN-GO) project ( 51 ).”
PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees (2012, methodology): “In addition, the PANTHER trees are being annotated with gene ontology (GO) (1) terms as part of the GO reference genome project (2,3), and these annotations are being deposited directly into the GO database.”