FALDO: a semantic standard for describing the location of nucleotide and protein feature annotation

Abstract

Background: Nucleotide and protein sequence feature annotations are essential to understand biology on the genomic, transcriptomic, and proteomic level. Using Semantic Web technologies to query biological annotations, there was no standard that described this potentially complex location information as subject-predicate-object triples.

Description: We have developed an ontology, the Feature Annotation Location Description Ontology (FALDO), to describe the positions of annotated features on linear and circular sequences. FALDO can be used to describe nucleotide features in sequence records, protein annotations, and glycan binding sites, among other features in coordinate systems of the aforementioned "omics" areas. Using the same data format to represent sequence positions that are independent of file formats allows us to integrate sequence data from multiple sources and data types. The genome browser JBrowse is used to demonstrate accessing multiple SPARQL endpoints to display genomic feature annotations, as well as protein annotations from UniProt mapped to genomic locations.

Conclusions: Our ontology allows users to uniformly describe - and potentially merge - sequence annotations from multiple sources. Data sources using FALDO can prospectively be retrieved using federalised SPARQL queries against public SPARQL endpoints and/or local private triple stores.

Keywords: Annotation; Data integration; RDF; SPARQL; Semantic Web; Sequence feature; Sequence ontology; Standardisation.

Fig. 1

The classes and object properties used in FALDO

Fig. 2

Assorted conventions for regions, start, end, and strands. This figure shows two hypothetical features on a DNA sequence (labeled chr1), on either the forward strand (orange) or reverse strand (blue). Using the INSDC location string notation, these regions are “1050..2080” and “complement(1050..2080)” respectively if implicitly given in terms of the reference chr1. Using the GTF/GFF3 family of formats, regardless of the strand these two locations are described with s t a r t=1050 and e n d=2080, and in general, s t a r t≤e n d. Biologically speaking, in terms of transcription, the start of a genomic feature is strand dependent. For the forward strand feature (orange), the start is 1050 while the reverse strand feature (blue) starts from 2080

Fig. 3

OWL2 property chain axiom to infer that all positions described in an INSDC record are relative to the main sequence of the record (in RDF turtle syntax, prefixes omitted)

Fig. 4

A SPARQL query to add all faldo:reference properties to faldo:positions described from a insdc:record

Fig. 5

JBrowse showing features, whose location is encoded using FALDO, selected via SPARQL (at e.g. http://togogenome.org/gene/1016998:SPAB_00296)

Fig. 6

Excerpt from UniProt entry Q6Q250 showing the position of an active site and a signal peptide in both the UniProt flat-file format and FALDO

Fig. 7

DDBJ record associated with UniProt Q6Q250 showing the related CDS sequence, with coding region outside of the known deposited mRNA sequence

Fig. 8

Using FALDO in Turtle [29] syntax to describe the location of a gene feature cheY at complement(NC_000913.2:1965072.. 1965461) in the INSDC record U00096.3

Fig. 9

Partial example of using FALDO in JSON-LD [30] syntax to describe the CDS “Protein II” at join(6006..6407,1..831) on J02448. Notice that this is given as a single location rather than being artificially split in two as in the INSDC join(...) notation

Fig. 10

FALDO representation of the HindIII restriction enzyme cleavage site with sticky ends