PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements

Abstract

The PANTHER database (Protein ANalysis THrough Evolutionary Relationships, http://pantherdb.org) contains comprehensive information on the evolution and function of protein-coding genes from 104 completely sequenced genomes. PANTHER software tools allow users to classify new protein sequences, and to analyze gene lists obtained from large-scale genomics experiments. In the past year, major improvements include a large expansion of classification information available in PANTHER, as well as significant enhancements to the analysis tools. Protein subfamily functional classifications have more than doubled due to progress of the Gene Ontology Phylogenetic Annotation Project. For human genes (as well as a few other organisms), PANTHER now also supports enrichment analysis using pathway classifications from the Reactome resource. The gene list enrichment tools include a new 'hierarchical view' of results, enabling users to leverage the structure of the classifications/ontologies; the tools also allow users to upload genetic variant data directly, rather than requiring prior conversion to a gene list. The updated coding single-nucleotide polymorphisms (SNP) scoring tool uses an improved algorithm. The hidden Markov model (HMM) search tools now use HMMER3, dramatically reducing search times and improving accuracy of E-value statistics. Finally, the PANTHER Tree-Attribute Viewer has been implemented in JavaScript, with new views for exploring protein sequence evolution.

Figure 1.

Reactome pathways in the PANTHER gene list analysis tool. Users can select Reactome pathways from a drop-down list of annotation sets. They can also upload a custom reference list for calculating overrepresentation by clicking on the ‘Change’ button. The Reactome pathways are accessible to both statistical test types in PANTHER: the overrepresentation tool (shown here) that takes a user-uploaded gene list as input, and the enrichment tool (not shown), that takes a user-uploaded list of genes, each of which is associated with a value, such as log-fold-change in expression or association P-value.

Figure 2.

Hierarchical view of GO (molecular function) in gene list analysis result page. Each block of related function classes (the first block starts with AMP-activated protein kinase activity, the second with acid-sensing ion channel activity) is arranged with the most specific class at the top, with less specific classes indented below it.

Figure 3.

Tree Viewer, showing the tree panel on the left, and multiple sequence alignment panel on the right with the ‘Evolutionary History’ view selected. This view shows in red text the amino acids that have changed in the tree branch immediately leading to each sequence. (A) The standard ‘phylogenetic view’ of the tree, showing only the sequences of the leaves (extant genes) of the tree. (B) The new ‘hierarchical view’ of the tree, showing the sequences of both internal nodes (inferred ancestral sequences) and leaves.