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To evaluate the regulatory relation between two genes, we modified the Pearson correlation coefficient.
Prior to defining a measure of similarity between two genes, we need to define similarity measures between the feature-sets corresponding to these genes.
Since similar codon bias can point to close functional relationships between two genes, we calculated the absolute difference between the CAI index values for tor2 and its targets and named the input feature CAI.diff.
To measure linear associations between two genes, we calculated the PCC values for all of the genes in a matrix of 8,377 × 8,377 (over 70 million combinations).
For each variant s i that shows significant association to a local gene g i, we test s i for association with distal genes g j that are nearby g i in the partial correlation network defined by G. Since the edges of G account only for direct relationships between two genes, we exploit the network structure to search for second-degree (downstream) regulatory effects as well.
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To investigate the role of other segment polarity genes in the mutual control between these two genes, we have examined wingless and engrailed protein distribution in embryos mutant for each of the segment polarity genes.
To further prioritize between these two genes, we consider a FLAGS-based approach.
To examine further the correlations between these two genes, we measured WTH3 gene expression levels in a cell line panel with defined p53 gene status.
Furthermore, although the phenomenon of mRNA-dependent interaction between the two genes we describe here occurs in cis, we currently have no reason to assume that similar interactions between RNAs cannot occur in trans as well.
To address the possibility of redundancy between these two genes, we performed double knockdown of vasa and tudor, which reduced transcripts of both genes to undetectable levels (Fig. 5E).
As the measure of functional similarity between the two genes we then calculated the ratio of the nodes found in both trees (intersection) and compared it to the union of both trees thus defining a similarity measure between 0 for unrelated genes and 1 for genes with identical annotations.
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