Identifying correlations between chromosomal proximity of genes and distance of their products in protein-protein interaction networks of yeast

Abstract

In this article we present evidence for a relationship between chromosome gene loci and the topological properties of the protein-protein interaction network corresponding to the set of genes under consideration. Specifically, for each chromosome of the Saccharomyces cerevisiae genome, the distribution of the intra-chromosome inter-gene distances was analyzed and a positive correlation with the distance among the corresponding proteins of the protein-protein interaction network was found. In order to study this relationship we used concepts based on non-parametric statistics and information theory. We provide statistical evidence that if two genes are closely located, then it is likely that their protein products are closely located in the protein-protein interaction network, or in other words, that they are involved in the same biological process.

Figure 1. Higher order chromatin structure: level 1, the double helix DNA; level 2, DNA wrapped around histone octamers to form nucleosomes (beads on a string); level 3, nucleosomes compacted into a chromatin fiber (i.e., the so-called 30 nm fiber).

Figure 2. The bp-distance between genes and is denoted as .

The ppi-distance is the shortest path between nodes of the corresponding PPI network indicated by . In this example the internode distance is equal to one so that is greater than .

Figure 3. Percentage of gene couples distances for the whole network (red plot) and for the same chromosome (green plot) for both networks considered: BIOGRID (lower panel) and MINT (upper panel).

Figure 4. Distributions of of shortest path distances for chromosomes 1–16 (from left top to right bottom) for both networks considered: BIOGRID (blue lines) and MINT (red lines).

Figure 5. Z-score values for each chromosomes in the BIOGRID network, computed by equation 5, are reported as function of the threshold

.

Figure 6. Z-score values for each chromosomes for MINT network, computed by equation 5, are reported as function of the threshold

.

Figure 7. BIOGRID: for each chromosome , , and (logarithmic scale).

In the lower panel horizontal dashed line represent a p-value equal to 0.05.

Figure 8. MINT: for each chromosome , , and (logarithmic scale). In the lower panel horizontal dashed line represent a p-value equal to 0.05.