View predictions by gene or function:
Predictions in FuncBase can be viewed either by function (GO term) or by gene. Users may search for their gene or function using a rich search syntax (Section 4
) permitting entry of gene or protein synonyms from multiple identifier systems, and text-matching within gene or function descriptions (A).
Fig. 1. Search (A) for an annotation report of a GO term (B) or gene (C). GO term reports show evidence of functional relationships (D) and function-related gene properties (E). The user may provide opinions (F) on any quantitative annotation. Gene reports also (more ...)
Both function and gene views (examples shown in B and C) allow predictions to be sorted by the confidence score from any available prediction method. GO annotations previously assigned by the corresponding species-specific authority are displayed next to each prediction.
View supporting evidence: Users may wish to further filter quantitative annotations based on their domain knowledge. Therefore, FuncBase displays key pieces of evidence underlying annotations.
Some annotation algorithms take a guilt-by-profiling approach—e.g. genes involved in ‘negative regulation of microtubule polymerization or depolymerization’ (GO:0031111) tend to contain a DH protein domain (InterPro pattern IPR000219). Therefore, each function view displays the gene properties that are most predictive of that function. A table (E), available by clicking an annotation row, indicates all properties held by the corresponding gene.
Some annotation algorithms take a guilt-by-association approach, in which GO annotations are ‘transferred’ between genes with evidence of a functional relationship (e.g. physical interaction between the corresponding proteins). Different variants of the functional linkage graphs are appropriate for different GO terms (see Taşan et al.
and Tian et al.
), so in function views one graph is displayed (D), and in gene views FuncBase three functional linkage graph versions are shown that correspond to the three branches of the GO (G). Functional linkage graphs can be viewed in FuncBase as static images, or manipulated within Cytoscape (Shannon et al.
Quantitative annotations from multiple sources: A unique feature of FuncBase is its ability to accommodate prediction sets from multiple bioinformatics teams differing by input data or algorithm. For example, 10 prediction sets are available for Mus musculus. We invite others to submit predictions associated with peer-reviewed publications for sharing via FuncBase.
User feedback: FuncBase is governed by the philosophy that annotation in general and predictive annotation in particular is a work in progress, and that users will often bring domain knowledge that supersedes current or predicted annotation. Therefore, for every gene/function combination displayed, a form invites expert users to provide feedback on whether they agree, disagree or are uncertain about this annotation (F). Free text notes can be attached to any opinion. Current tallies of true and false responses are shared among all users and made available in summary form to the appropriate species authority. Community feedback on predictions gathered and shared in real time is novel to the FuncBase quantitative annotation resource.