Table 4.

The 23 GO MF annotations used in the proposed method

GO ID	GO MF Annotation
GO:0003674	Molecular function unknown
GO:0016740	Transferase activity
GO:0016787	Hydrolase activity
GO:0030528	Transcription regulator activity
GO:0005198	Structural molecule activity
GO:0005215	Transporter activity
GO:0005515	Protein binding
GO:0003677	DNA binding
GO:0003723	RNA binding
GO:0016491	Oxidoreductase activity
GO:0030234	Enzyme regulator activity
GO:0004672	Protein kinase activity
GO:0006874	Ligase activity
GO:0008233	Peptidase activity
GO:0016779	Nucleotidyltransferase activity
GO:0004871	Signal transducer activity
GO:0004386	Helicase activity
GO:0006874	Ligase activity
GO:0045182	Translation regulator activity
GO:0016853	Isomerase activity
GO:0004721	Phosphoprotein phosphatase activity
GO:0003774	Moter activity
Other	Other

Molecular function unknown (GO: 0003674) from the GO slim annotation terms was included in the set of annotations for the calculation of LOI scores. In the yeast genome, there are nearly two thousand genes (about one third of the genome) that have the annotation 'molecular function' according to the SGD. From the set of interactions identified by 'Pathway Studio', nearly 15% involve a target or regulator of the annotation 'molecular function unknown'. Although a gene product's annotation may not yet characterized, it still can participate in biologically meaningful interactions for the analysis of microarray data. The consideration of the frequency at which a gene with undermined function is involved in an interacting partner with known annotations allows the LOI-method for the potential identification of useful biological interactions even when the function of one of the genes remains unknown. Ideally, as biological information of an organism's entire set of expressed proteins becomes known, the necessity of including an annotation of unknown molecular function will vanish.