A B 3212 1136 3177 Biological Process

1771

8799 16381 6117 19098 9481 17775 1896 1750 3382 502 Biological Process Cellular Component Molecular Function 3720 483

Experimentally Predicted Unknown Cellular Component Molecular Function validated

Figure S1. Status of the functional annotation of the 28392 Arabidopsis thaliana genes on November 2015. A) The pie charts show the fraction of experimentally validated (green), predicted (blue) and unknown function (gray) genes for BP, CC and MF. B) Venn diagram showing the overlap of functionally characterized genes in the three domains of GO. Biological process Number of integrated networks F-measure

Number of made predictions

Cellular Component Number of integrated networks F-measure

Number of made predictions

Molecular function Number of integrated networks F-measure

Number of made predictions Figure S2. Combinatorial analysis of the ten gene co-function networks for BP (top), CC (middle) and MF (bottom). The x-axis indicates the number of made predictions, while the y-axis shows the F-measure. Point color indicates the number of integrated networks, ranging from 1 network (dark blue) to ten (bright yellow). MF (bottomright). confidence intervalplotsof100permutations. The linesrepresentbootstrapped68% (x-axis)forBPpredictions (y-axis)and%ofgeneswithavailable GOterms (topright),CC(middleeight)and given forBP (topleft),CC(middleleft)andMF(bottomleft).Relationship betweenthenumberofmade predictions. Figure S3.Influenceofavailablefunctional information onF-measureandthenumberofmade F-measure F-measure F-measure Relationship between the F-measure (y-axis) and%ofgeneswithavailableGOterms(x-axis) RelationshipbetweentheF-measure(y-axis) Cellular Component % ofgeneswithGeneOntologyterm % ofgeneswithGeneOntologyterm % ofgeneswithGeneOntologyterm Molecular function Biological process

Made predictions Made predictions Made predictions % ofgeneswithGeneOntologyterm % ofgeneswithGeneOntologyterm % ofgeneswithGeneOntologyterm Cellular Component Biological process Molecular function GeneMANIA (bottom),BP. the phylostrataofgenes(x-axis). Figure S4Relationshipbetweenthepercentage ofgeneswithaneighborinnetwork(y-axis)and

% of genes with a neighbor % of genes with a neighbor Green plants Vascular plants Land plants Eudicots Angiosperms Phylostrata GeneMANIA Biologicalprocess ATTED-II Biologicalprocess Phylostrata Arabidopsis thaliana Brassicales Malvids Arabidopsis Rosids The exampleisgivenfor ATTED-II (top), AraNet v2(middle)and

% of genes with a neighbor % of genes with a neighbor % of genes with a neighbor BIOGRID Biologicalprocess RNAseq Biologicalprocess Phylostrata Phylostrata Phylostrata AraNet v2Biologicalprocess A B

ExperimentallyNetwork 1 Network 2 Network 3 Experimentally Network 1 Network 2 Network 3 verified functionprediction prediction prediction verified functionprediction prediction prediction

Gene 1 Gene A

Gene 2 Gene B

Gene 3 Gene C

Figure S5. Estimating the performance of Gene Ontology term predictions. A) An example of a GO term that can be predicted well. Three genes (1-3) experimentally assigned to the term are predicted to be assigned to this term in 9 cases (indicated by green +). B) An example of a GO term that cannot be predicted well. Only 2 out of 9 networks predicted that the experimentally assigned genes A-C are assigned to this term. Number of gene pairs

Gene Ontology Jaccard Index value

Figure S6 Estimating the significant Gene Ontology Jaccard Index (GOJI) value. The histogram shows the relationship between GOJI values (x-axis) and frequency of random gene pairs showing the particular value. The red line indicates the GOJI threshold (0.178) below which 99% of the random pairs are found.