Results: 4

1.
Figure 3

Figure 3. From: Conserved rules govern genetic interaction degree across species.

Observed genetic interactions between S. pombe genes support degree predictions. (a) Model predictions were validated on a second, whole-genome set of interaction screens in S. pombe that are independent of the training data. Eight query deletion mutants were crossed with the entire non-essential deletion collection in S. pombe. In total, genetic interaction (epsilon) scores were measured for approximately 23,000 gene pairs. Epsilon scores are tightly centered at 0, thus interactions called for scores of ± 0.08 or more extreme are rare. (b) The collection of non-essential S. pombe genes (n = 2,907) were grouped by the number of interactions each has with the eight query genes for which full-genome screens were performed. Numbers in parentheses give the number of genes for which this degree was observed. For each degree, the box plot shows the distribution of predicted degrees, which are expressed as percentiles. There is a strong positive correlation (Pearson's r = 0.40, P < 10-111) between predicted and actual degree.

Elizabeth N Koch, et al. Genome Biol. 2012;13(7):R57-R57.
2.
Figure 1

Figure 1. From: Conserved rules govern genetic interaction degree across species.

Physiological and evolutionary gene features are predictive of genetic interaction degree. (a) Gene features are significantly correlated with negative genetic interaction degree. We measured the Pearson correlation coefficients between gene feature values and negative genetic interaction degree for 3,456 non-essential S. cerevisiae genes. Error bars show 95% confidence intervals. A complete set of features and their correlations is given in Table 1; see Materials and methods for descriptions of gene features. (b) Overview of the regression tree model for genetic interaction degree. An ensemble of 100 decision trees was built from bootstrap samples of genes. Combinations of values of features are represented as paths from the root to the leaves of a tree. Internal nodes each split data (sets of genes) according to values for a single feature; leaf nodes are associated with predicted genetic interaction degrees. (c) Scatter plot of negative genetic interaction degree and degrees predicted by the bagged decision tree model on held-out genes shows the significant relationship between predicted and actual degrees (Pearson's r = 0.80, P < 10-324). FD, fitness defect; PPI, protein-protein interaction; SM, single mutant.

Elizabeth N Koch, et al. Genome Biol. 2012;13(7):R57-R57.
3.
Figure 2

Figure 2. From: Conserved rules govern genetic interaction degree across species.

Cross-species analysis of the predictive model for genetic interactions. (a) Pearson correlations between one-to-one S. cerevisiae and S. pombe orthologs for their values of gene features. Note that a number of features are sequence-based and are thus not independent of the sequence-based ortholog identification; features that appear to have trivial correlations are not included here. Error bars show 95% confidence intervals. (b) Pearson correlations between features and degree in S. pombe are observed to be significant in many cases and similar to those in S. cerevisiae. A complete set of features and their correlations is given in Table 1; see Materials and methods for descriptions of gene features. Error bars show 95% confidence intervals. (c) Predictive abilities of bagged regression tree models were evaluated by measuring Pearson correlations between predicted and actual degrees. The left set of bars shows the performance of predictions made for approximately 550 S. pombe genes and the right set of bars shows the performance of predictions made for all non-essential deletion mutants in S. cerevisiae. For each scenario, models were trained both on data from the same species (red bar) as well as data from the other species (blue bars). The light blue bars correspond to predicting degrees of all genes in the test species, while the dark blue bars correspond to predicting degrees of genes in the subset of genes lacking orthologs in the training species. Error bars show standard deviations of bootstrapped predictions. For a baseline, the dashed line shows the correlation between observed degrees of one-to-one orthologous genes (a simple prediction method that can be applied to only orthologs). CAI, Codon Adaptation Index; PPI, protein-protein interaction; SM, single mutant.

Elizabeth N Koch, et al. Genome Biol. 2012;13(7):R57-R57.
4.
Figure 4

Figure 4. From: Conserved rules govern genetic interaction degree across species.

Global analysis of rewiring based on whole-genome predictions in S. pombe. (a) Points in the scatter plot each represent groups of between 2 and 22 genes whose protein products are in the same protein complex (Materials and methods). Darker color represents complexes that are predicted to have significant rewiring. Generally, genes in complexes that fall on the diagonal are predicted to have conserved degrees, while those that fall off-diagonal show evidence for large degree differences between the two species. Significantly rewired complexes (at a threshold of 0.05) are labeled by their names. (b) To validate our predicted rewired genes, we constructed separate networks of co-expression relationships among genes for each yeast species, then labeled genes according to our rewiring designation. Only one-to-one orthologs that are non-essential in both species were included in the networks. Edges in the co-expression network were classified by whether involved genes were both rewired, only one was rewired, or neither was rewired. We then calculated fractions of conserved co-expression relationships between species within each of these classes. (c) There is a clear relationship between these classes of edges and their conservation across the two yeast species. For rewiring at four levels of magnitude, we counted the number of conserved edges (among all edges in the union of the two networks). A conserved edge appears in the networks of both species and a non-conserved edge appears in exactly one. The magnitude of rewiring increases along the x-axis for the rewired class (differences of > 30, > 55, > 80, > 105 interactions), but the non-rewired class is defined as the set of ortholog pairs with less than a 30-edge difference in degree. Edges in the two rewired classes consistently showed significantly lower levels of conservation than edges in the non-rewired class (P < 0.01, Fisher's exact test). Error bars show the binomial proportion 95% confidence interval. The dashed line is the expected rate of conservation if edges are randomized in one of the co-expression networks. There are 12,472 edges among 509 genes in the conserved-conserved network. Numbers of edges and genes at rewiring thresholds, in bold, are as follows, where the conserved-rewired case is given as the first pair and the rewired-rewired case is given second: 30: (14532, 832), (4684, 323); 55: (8730, 695), (1659, 186); 80: (5358, 620), (644, 111); 105: (2822, 565), (176, 56).

Elizabeth N Koch, et al. Genome Biol. 2012;13(7):R57-R57.

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