Pipeline output for FOXA factor group, an example that highlights different aspects of the resource (in the interest of space, only selected columns are shown in the enlargements). (a) The known and discovered motifs for the factor group, drawn with WebLogo (). Because the original orientation is arbitrary, motifs are flipped as necessary to increase the similarity of the displayed orientations. (b and c) Similarity between the motifs for this factor group and the motifs: (b) for this factor group, (c) for all other motifs that match at least one motif for this factor group with similarity . Motif similarities are shown in black/white scale with gray starting at 0.65. (d) Enrichments of motifs in the data sets for this factor group. Data sets are named indicating the factor, cell type/stage, lab code, followed by values to differentiate data sets and make them unique. Red is used for enrichment, blue is used for depletion (which is rare in this study). Enrichments are not shown for motifs when control motifs could not be generated or there was not sufficient information content to match at a P-value. (e) Magnified enrichment heatmap value. The three triangles represent the background regions used for enrichment; the top triangle is all regions, the left triangle is those within 2 kb of an annotated TSS and the right triangle is those outside the 2 kb window (the regions used in the left and right triangles partition that of the top triangle). The number shown is the enrichment in the inclusive background. Here we see an apparent contradiction: a higher enrichment for the union than the parts. This occurs because the higher counts permit a smaller confidence interval around the ratios used to compute the enrichment. Heatmaps are ordered using hierarchical clustering followed by optimal leaf ordering (). The Supplementary Results include an analysis of the robustness of the motif similarity metric and the enrichment values.

Outline of motif discovery pipeline. Input regions for each data set are randomly partitioned into two groups. The top 250 regions of one of the partitions are scanned for motifs using five de novo motif discovery tools. These motifs are evaluated using the peaks from the other partitioned and pooled across data sets for a factor group to produce the final list of discovered motifs for each factor group.

(a) Summary of input data used. The outside ring indicates the experimental data sets (one tick for each of 427), which are separated into 123 transcription factors (second ring). The TFs are further grouped into 84 factor groups (third ring). We are able to find a matching discovered motif for 41 of the 56 factor groups with a known motif; 29 of these 41 factor groups have additional discovered motifs that may be associated with cofactors. For all but 1 of the 15 factor groups where the known motif is not recovered we still find enriched discovered motifs. We also discovered enriched motifs for 17 of the 28 factor groups without a known motif. (b) Recovery of known motifs by each of the discovery tools. Performance of discovery in terms of number of factor groups for which the known motif was recovered. A motif is considered a match if it matches any of the known motifs for a factor group (see Supplementary Methods for details on how matches are computed). The number of additional factors that have a match is shown with each additional motif (only three motifs are taken from each individual method, whereas we have up to 10 for the pipeline). The number of factor groups with no motif match is shown in parenthesis. When multiple data sets exist for a factor group, the fraction that matches is used in computing its contribution for computing the performance of the individual tools.

Comparison of known versus discovered motifs (selected where discovered better enriched than known; all factor groups with a discovered motif matching a known motif in Supplementary Table S3). Displayed is the known and discovered motif with the maximum enrichment across all data sets for a factor group. Only the discovered motifs that match a known motif for a factor group are considered. The maximum enrichment is indicated for each factor and, in parenthesis, the ‘raw’ enrichment for the same data set without the use of the shuffle motifs for correction.

Putative novel motifs. We find eight motifs that are not represented in the literature motifs we collected, three of which are found for at least two factor groups. These patterns may represent the binding specificity of the factors for which they are discovered or for other factors that cooperate with them.