Argot2: a large scale function prediction tool relying on semantic similarity of weighted Gene Ontology terms.

Background: Predicting protein function has become increasingly demanding in the era of next generation sequencing technology. The task to assign a curator-reviewed function to every single sequence is impracticable. Bioinformatics tools, easy to use and able to provide automatic and reliable annotations at a genomic scale, are necessary and urgent. In this scenario, the Gene Ontology has provided the means to standardize the annotation classification with a structured vocabulary which can be easily exploited by computational methods.
Results: Argot2 is a web-based function prediction tool able to annotate nucleic or protein sequences from small datasets up to entire genomes. It accepts as input a list of sequences in FASTA format, which are processed using BLAST and HMMER searches vs UniProKB and Pfam databases respectively; these sequences are then annotated with GO terms retrieved from the UniProtKB-GOA database and the terms are weighted using the e-values from BLAST and HMMER. The weighted GO terms are processed according to both their semantic similarity relations described by the Gene Ontology and their associated score. The algorithm is based on the original idea developed in a previous tool called Argot. The entire engine has been completely rewritten to improve both accuracy and computational efficiency, thus allowing for the annotation of complete genomes.
Conclusions: The revised algorithm has been already employed and successfully tested during in-house genome projects of grape and apple, and has proven to have a high precision and recall in all our benchmark conditions. It has also been successfully compared with Blast2GO, one of the methods most commonly employed for sequence annotation. The server is freely accessible at http://www.medcomp.medicina.unipd.it/Argot2.