In brief, starting with the mouse datasets, we first partitioned the induced genes into disjoint groups according to the subset of stimulators to which the genes were responsive.
The first study, by Nau et al. [ 9], examined expression profiles in human monocyte-macrophages at several time points (1 hr, 2 hrs, 6 hrs, 12 hrs and 24 hrs) after stimulation by various agents; among them LPS and PIC are common to the stimuli examined by the mouse datasets we analyzed (this dataset is hereafter called HsM1).
Following the analysis applied to the mouse datasets, we partitioned the genes induced by LPS and PIC in the human datasets to the three kinetic sets: 'EE'ED'ED' and 'DD' (again, using the 2 hr time point as the boundary between early and delayed time points), according to the kinetics of their activation, and searched for over-represented signals in the promoters of these gene sets.
For the human-mouse dataset we observe that the number of true positives increases rapidly as α increases and then decreases at the same rate after reaching a maximum of 14133 when α is 0.53.
In our updated mouse KO dataset, we compiled 211 singleton mouse KO targeted genes with available protein connectivity data, as well as 845 mouse KO duplicates [ 26].
In the complete mouse promoter dataset, we identified 29 significant motifs corresponding to matches to TRANSFAC matrices, 4 to JASPAR CORE matrices, 9 to JASPAR phyloFACTS, and 22 to 6mers.
In contrast to the results found on the mouse dataset (Table 3), we did not detect here an over-representation of ATF/CREB in the 'EE' set (representing early induction and peak).
In agreement with the results obtained on the mouse dataset, here too we observed a strong enrichment for NF-κB and ISRE elements in the 'ED' (early induction, delayed peak) and 'DD' (delayed induction and peak) sets, respectively (Table 5).
The yeast regulatory system is simpler, recombination rates are higher, and the number of available samples is greater than in the recombinant inbred mouse dataset currently available; therefore, we focus on the work of Brem and colleagues exclusively.
When we analyzed the expression levels of those potential map partners in the original mouse brain injury dataset, we found that several of these genes for instance, Bcr, Unc13b, IL3, and Pip5k1c were either expressed at very low levels or unexpressed.
