Functional related genes tend to be spatially clustered in both fission yeast and budding yeast.

<p><b>(A)</b> Spatial clustering of functional related genes in fission and budding yeast. The histogram shows the distribution of the mean pair distance ratio between a set of functionally related genes, as defined by genetic interaction experiments (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119672#pone.0119672.s006" target="_blank">S1 Text</a>) and all the sites in the structures population. The histograms are generated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119672#pone.0119672.g002" target="_blank">Fig. 2D</a>. Genes with low functional correlation score are less clustered compared to related genes with high functional correlation. The Cohen’d for highly functional correlated gene pairs is 1.34 and 3.85 for the fission yeast and the budding yeast (p-value<1E-16 for both cases). The Cohen’d for lowly functional correlated genes is 0.13 and 2.17 for the fission yeast and the budding yeast, respectively (p-value<1E-16 for both cases). <b>(B)</b> Histograms of the distributions of the mean pair distance ratio between the set of early replication origins and all the sites in the structure population. A corresponding histogram is shown also for late replication origins. Early replication origins are spatially clustered in fission yeast (p-value<1E-16, Cohen’d = 0.59), while late replication site show statistically significant larger average distances than randomly selected sites (p-value<1E-16, Cohen’d = 0.4) <b>(C)</b> Comparison of the clustering of genes in the same GO categories between fission yeast and budding yeast. The test is based on 51 GO categories, which contain sufficient amount of genes in both yeast types. Plotted is the difference D_GO—D_random between the average pairwise 3D distances of the genes in a GO category (D_GO) and the average pairwise 3D distances between randomly selected gene sites (D_random). If the difference D_random-D_GO is larger than 0, genes in the GO category is defined as clustered (p-value<-1E16), and If the difference is smaller than 0, genes in the GO category are considered to be”dispersed” (p-value<-1E16). Each point representing a GO category is colored by their functional categories, such as cellular component, biological process and molecular function. <b>(D)</b> The clustering of functional categories is highly significant. Shown is a selection of GO categories under the term molecular functions. The dashed line indicates a p-value of 1E-16. The—log(p-value) is trimmed at maximally p-value = 1E-20. The numbers on the left of the figure represent GO categories as labeled in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119672#pone.0119672.s007" target="_blank">S1 Table</a>. For all the genes in the class “Molecular Function”, 10 of 10 GO categories are significantly clustered in budding yeast, while genes in 7 out of the 10 same GO categories are significantly clustered in fission yeast.</p

Fission yeast genome structures calculation.

<p><b>(A)</b> Schematic view of fission yeast nuclear architecture and imposed geometric constraints. Centromeres are located within a sphere volume of radius 300 nm to ensure that they are close to the SPB. Telomeres are anchored to the NE and can freely move on the NE surface. rDNA genes are constrained to be on the nucleolar surface (right side). All non-rDNA genes are prevented to enter the nucleolus. All chromosomes are confined in a nucleus of radius 0.71 micron. <b>(B)</b> Snapshot of a genome structure illustrating the packing of the chromosomes in the nuclear volume. Different chromosome chains are depicted in different colors. The nucleolus volume is shown in silver. The spindle pole body is shown as a light green cylinder opposite to nucleolus. <b>(C,D,E)</b> Heatmaps of the genome-wide contact frequencies of the fission yeast from calculated structure populations (<b>C</b>), from experiment (<b>D</b>), and from a random control model with no geometric constraints applied (<b>E</b>). The resolution of the heatmaps is 96 kb per bin (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119672#pone.0119672.s001" target="_blank">S1 Text</a>). The color code ranges from white to red to represent frequencies from low to high. The telomere-telomere interactions are highlighted in a zoom-in box <b>(F)</b> Pearson correlation between contact frequency heat maps from experiment and structure populations (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119672#pone.0119672.s001" target="_blank">S1 Text</a>). Correlation values are shown for intra-chromosomal and inter-chromosomal interactions separately. The experimental heat map is compared to several different structure populations generated with different amount of geometric constraints. Values for models C, R, N indicate structure populations that were generated only with centromeric constraints (C), rDNA constraints (R) and telomere anchoring constraints (N), respectively (Methods).</p

Comparative 3D Genome Structure Analysis of the Fission and the Budding Yeast

<div><p>We studied the 3D structural organization of the fission yeast genome, which emerges from the tethering of heterochromatic regions in otherwise randomly configured chromosomes represented as flexible polymer chains in an nuclear environment. This model is sufficient to explain in a statistical manner many experimentally determined distinctive features of the fission yeast genome, including chromatin interaction patterns from Hi-C experiments and the co-locations of functionally related and co-expressed genes, such as genes expressed by Pol-III. Our findings demonstrate that some previously described structure-function correlations can be explained as a consequence of random chromatin collisions driven by a few geometric constraints (mainly due to centromere-SPB and telomere-NE tethering) combined with the specific gene locations in the chromosome sequence. We also performed a comparative analysis between the fission and budding yeast genome structures, for which we previously detected a similar organizing principle. However, due to the different chromosome sizes and numbers, substantial differences are observed in the 3D structural genome organization between the two species, most notably in the nuclear locations of orthologous genes, and the extent of nuclear territories for genes and chromosomes. However, despite those differences, remarkably, functional similarities are maintained, which is evident when comparing spatial clustering of functionally related genes in both yeasts. Functionally related genes show a similar spatial clustering behavior in both yeasts, even though their nuclear locations are largely different between the yeast species.</p></div

Nuclear accessibility for orthologous genes in the fission yeast and the budding yeast.

<p>The orthologous of URA3 in budding yeast is URA4 in fission yeast.</p><p>Nuclear accessibility for orthologous genes in the fission yeast and the budding yeast.</p

Constraints applied for different models.

<p>In total we generate 5 different models with different combination of specific geometric restraints (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119672#pone.0119672.t001" target="_blank">Table 1</a>). A check mark indicates that a model contains the corresponding set of constraints.</p><p>Constraints applied for different models.</p

Chromosome and gene territories analysis of fission yeast and budding yeast.

<p><b>(A)</b> Chromosome localization probability density (LPD) plots for fission yeast (top panel) and selected chromosomes in budding yeast for comparison (lower panel)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119672#pone.0119672.ref029" target="_blank">29</a>]. The chromosomes are ordered by their size from largest (left) to smallest chromosomes (right). (<b>B</b>) Comparison of the nucleus accessibility of genomic regions between fission yeast and budding yeast (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119672#pone.0119672.s001" target="_blank">S1 Text</a>). The higher the accessibility, the more space it can explore the nucleus. The red dots in red represent the centromeric locations. (<b>C</b>) Gene localization probability density (LPD) plots for four genes in fission yeast. Their orthologous genes were also analyzed in the budding yeast genome models [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119672#pone.0119672.ref029" target="_blank">29</a>].</p

An integrative approach to characterize disease-specific pathways and their coordination: a case study in cancer-0

<p><b>Copyright information:</b></p><p>Taken from "An integrative approach to characterize disease-specific pathways and their coordination: a case study in cancer"</p><p>http://www.biomedcentral.com/1471-2164/9/S1/S12</p><p>BMC Genomics 2008;9(Suppl 1):S12-S12.</p><p>Published online 20 Mar 2008</p><p>PMCID:PMC2386054.</p><p></p