Gene Ontology-driven inference of protein-protein interactions using inducers

Motivation: Protein-protein interactions (PPI) are pivotal for many biological processes and similarity in Gene Ontology (GO) annotation has been found to be one of the strongest indicators for PPI. Most GO-driven algorithms for PPI inference combine machine learning and semantic similarity techniques. We introduce the concept of inducers as a method to integrate both approaches more effectively, leading to superior prediction accuracies.

Results: An inducer (ULCA) in combination with a Random Forest classifier compares favorably to several sequenced-based methods, semantic similarity measures and multi-kernel approaches. On a newly created set of high-quality interaction data, the proposed method achieves high cross-species prediction accuracies (AUC ≤ 0.88), rendering it a valuable companion to sequence-based methods.

Availability: Software and datasets are available athttp://bioinformatics.org.au/go2ppi/

Improving gene annotation using peptide mass spectrometry

Tanner S, Shen Z, Ng J, Florea L, Guigó R, Briggs SP, Bafna V . Genome Research, 2007, 17(2)

Annotation of protein-coding genes is a key goal of genome sequencing projects. In spite of tremendous recent advances in computational gene finding, comprehensive annotation remains a challenge. Peptide mass spectrometry is a powerful tool for researching the dynamic proteome and suggests an attractive approach to discover and validate protein-coding genes. We present algorithms to construct and efficiently search spectra against a genomic database, with no prior knowledge of encoded proteins. By searching a corpus of 18.5 million tandem mass spectra (MS/MS) from human proteomic samples, we validate 39,000 exons and 11,000 introns at the level of translation. We present translation-level evidence for novel or extended exons in 16 genes, confirm translation of 224 hypothetical proteins, and discover or confirm over 40 alternative splicing events. Polymorphisms are efficiently encoded in our database, allowing us to observe variant alleles for 308 coding SNPs. Finally, we demonstrate the use of mass spectrometry to improve automated gene prediction, adding 800 correct exons to our predictions using a simple rescoring strategy. Our results demonstrate that proteomic profiling should play a role in any genome sequencing project.