BMC Genomics 2008, 9(Suppl 2):S20 http://www.biomedcentral.com/1471-2164/9/S2/S20 IFlliugsutrraeti3on of the steps in the semi-supervised functional module discovery process Illustration of the steps in the semi-supervised functional module discovery process. This figure shows the various step of the functional module discovery algorithm. This algorithm is related to the BALBOA algorithm and begins in the same manner with the dataset splitting in step 1 and the bicluster analysis of the annotated genes only in step 2. In step 3 however all biclusters are selected for analysis. In step 4 dataset cross validation is carried out to establish groups of ORFs that are consist- ently grouped together by biclusters over the three datasets. In step 5 these consistently grouped unclassified ORFs are returned as predicted functional modules, where the function may be inferred by the enrichment and significance of the domi- nant functional class in the classifying biclusters. datasets the predicting annotated bicluster was signifi- cantly functionally enriched for genes from the Ribosomal RNA processing (11.04.01) functional category with p-val- ues of 2.61 × 10-11, 1.53 × 10-14 and 1.24 × 10-8 in the Eisen, Gasch and Hughes datasets respectively. Eisen and Gasch biclusters were also enriched to a lesser extent in Ribosome biogenesis (12.01) genes, 2.66 × 10-6 and 2.08 × 10-7 respectively. Interestingly, YDL167C, YDR361C, YJR003C and YLR196W were individually predicted to be involved in these processes by BALBOA in the last section. Further physical/genetic association and functional evi- dence from the SGD is provided in Table 3. Another set of unclassified ORFs consistently grouped together across the three expression datasets is YBL112C, YEL076C, YER189W, YHR219W These are predicted by annotated biclusters highly enriched for the DNA Topology (10.01.02) functional category with p-values of 7.26 × 10- 29, 6.58 × 10-14 and 2.89 × 10-7 in the Eisen, Gasch and Hughes expression datasets respectively. The correlated expression of this group of unclassified ORFs, across all three datasets, can be seen in Figure 5. In Table 3 we see that these ORFs are located in the telomeric regions and YHR219W has some similarity to helicases. Another set of unclassified ORFs, consistently predicted by annotated biclusters across the Hughes and Gasch Page 11 of 15 (page number not for citation purposes)