Mlc1 and Act1 are static hubs with some dynamic partners.

<p>(<b>A</b>) Graph of expression ratios in the cell cycle, over time, showing non-periodic expression of Act1 and Mlc1 and their interaction partners. Red dotted line indicates threshold used in the network analysis. (<b>B</b>) Frames from the real-time rendering animation (threshold −0.2) from the network of Mlc1 and Act1 and their interaction partners. At each time point, nodes (representing proteins) map gene expression data from the cell cycle to a green/black/red color gradient. Proteins and their interactions are hidden when their expression at any point in time falls below the threshold. Act1 and Mlc1 are present throughout the animation, but some of their interaction partners are not. When interaction partners are present, they are suggested to not compete with each other to interact with Act1 and/or Mlc1 due to their staggered expression peaks.</p

Gdi1 is a static hub with a few dynamic interaction partners.

<p>(<b>A</b>) Graph of expression ratios in the cell cycle, over time, showing non-periodic expression of Gdi1 and its interaction partners. Red dotted line indicates threshold used in the network analysis. (<b>B</b>) Frames from the real-time rendering animation (threshold −0.2) from the network of Gdi1 and its interaction partners. At each time point, nodes (representing proteins) map gene expression data from the cell cycle to a green/black/red color gradient. Proteins and their interactions are hidden when their expression at any point in time falls below the threshold. The dynamic interaction partners of Gdi1 will compete with other proteins only when expressed at the same time.</p

Cln1-3 and Clb1-6 are dynamic hubs with many static interaction partners.

<p>(<b>A</b>) Graph of expression ratios in the cell cycle, over time, showing periodic expression of cyclin Clb5 and its interaction partners. Dynamic interaction partners shown in color and static interaction partners are in gray. Red dotted line indicates threshold used in the network analysis. (<b>B</b>) Frames from the real-time rendering animation (threshold −0.2) from the network of the cyclins Cln1-3 and Clb1-6 and their interaction partners. At each time point, nodes (representing proteins) map gene expression data from the cell cycle to a green/black/red color gradient. Proteins and their interactions are hidden when their expression at any point in time falls below the threshold. When each cyclin is present, many of their interaction partners are as well, suggesting that they will compete with each other to interact with the cyclins.</p

Singlish hub proteins.

a<p>Number of interactions interfaces as described by Kim <i>et al.</i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048209#pone.0048209-Kim1" target="_blank">[10]</a>.</p>b<p>Domains and abbreviations thereof from Pfam <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048209#pone.0048209-Punta1" target="_blank">[25]</a>.</p>c<p>Hub classified as ‘Dynamic’ if it shows periodic expression throughout the cell cycle. Hub classified as ‘Static’ if it has non-periodic expression throughout the cell cycle and it has at least one periodic interaction partner. Hubs with missing or low quality expression data not classified, and are shown with a hyphen.</p

Cla4 is a dynamic hub with many static interaction partners.

<p>(<b>A</b>) Graph of expression ratios in the cell cycle, over time, showing periodic expression of Cla4 and its dynamic interaction partners. Red dotted line indicates threshold used in the network analysis. (<b>B</b>) Frames from the real-time rendering animation (threshold −0.1) from the network of Cla4 and its interaction partners. At each time point, nodes (representing proteins) map gene expression data from the cell cycle to a green/black/red color gradient. Proteins and their interactions are hidden when their expression at any point in time falls below the threshold. When Cla4 is present, many of its interaction partners are also expressed, suggesting that they will compete with each other to interact with Cla4 at those times. (<b>C</b>) Network of Cla4, its interaction partners, and their interactions with each other. This demonstrates the competition that Cla4, Gic1 and Gic2 may have in their interaction with Cdc42.</p

Cdc28 and Pho85 are static hubs with many dynamic interaction partners.

<p>(<b>A</b>) Graph of expression ratios in the cell cycle, over time, showing non-periodic expression of the CDKs Cdc28 and Pho85 and the dynamic cyclins they interact with. Red dotted line indicates threshold used in the network analysis. Cyclins that act redundantly with other cyclins have not been shown (Cln2, Clb2,4,6). (<b>B</b>) Frames from the real-time rendering animation (threshold −0.2) from the network of Cdc28 and Pho85 and their interacting cyclins. At each time point, nodes (representing proteins) map gene expression data from the cell cycle to a green/black/red color gradient. Proteins and their interactions are hidden when their expression at any point in time falls below the threshold. The CDKs are present throughout the cell cycle, but their cyclins are not. Thus the cyclins do not have to compete with all the other cyclins to interact with a CDK but only those expressed at similar times.</p

Investigating the Network Basis of Negative Genetic Interactions in <i>Saccharomyces cerevisiae</i> with Integrated Biological Networks and Triplet Motif Analysis

Negative genetic interactions in <i>Saccharomyces cerevisiae</i> have been systematically screened to near-completeness, with >500 000 interactions identified. Nevertheless, the biological basis of these interactions remains poorly understood. To investigate this, we analyzed negative genetic interactions within an integrated biological network, being the union of protein–protein, kinase–substrate, and transcription factor–target gene interactions. Network triplets, containing two genes/proteins that show negative genetic interaction and a third protein from the network, were then analyzed. Strikingly, just six out of 15 possible triplet motif types were present, as compared to randomized networks. These were in three clear groups: protein–protein interactions, signaling, and regulatory triplets where the latter two showed no overlap. In the triplets, negative genetic interactions were associated with paralogs and ohnologs; however, these were very rare. Negative genetic interactions among the six triplet motifs did however show strong dosage constraints, with genes being significantly associated with toxicity on overexpression and periodicity in the cell cycle. Negative genetic interactions overlapped with other interaction types in 37% of cases; these were predominantly associated with protein complexes or signaling events. Finally, we highlight regions of “network vulnerability” containing multiple negative genetic interactions; these could be targeted in fungal species for the regulation of cell growth

Number of new genes identified in the assemblies of clinical isolates, <i>L. rhamnosus</i> LRHMDP2 and <i>L. rhamnosus</i> LRHMDP3^a.

a<p>based on comparative studies with reference probiotic <i>L. rhamnosus</i> strains ATCC53103 (GG) and Lc705.</p>b<p>inclusive of 176 genes coding for hypothetical proteins.</p>c<p>inclusive of 166 genes coding for hypothetical proteins.</p

Comparative Genome Analysis of <i>Lactobacillus rhamnosus</i> Clinical Isolates from Initial Stages of Dental Pulp Infection: Identification of a New Exopolysaccharide Cluster

<div><p>The human oral microbiome has a major role in oral diseases including dental caries. Our studies on progression of caries infection through dentin and more recently, the invasion of vital dental pulp, detected <i>Lactobacillus rhamnosus</i> in the initial stages of infection of vital pulp tissue. In this study employing current high-throughput next generation sequencing technology we sought to obtain insight into genomic traits of tissue invasive <i>L. rhamnosus</i>, to recognise biomarkers that could provide an understanding of pathogenic potential of lactobacilli, generally regarded as safe. Roche GS FLX+ technology was used to generate whole genome sequences of two clinical isolates of <i>L. rhamnosus</i> infecting vital pulp. Detailed genome-wide comparison of the genetic profiles of tissue invasive <i>L. rhamnosus</i> with probiotic <i>L. rhamnosus</i> was performed to test the hypothesis that specific strains of <i>L. rhamnosus</i> possessing a unique gene complement are selected for the capacity to invade vital pulp tissue. Analysis identified 264 and 258 genes respectively, from dental pulp-invasive <i>L. rhamnosus</i> strains LRHMDP2 and LRHMDP3 isolated from two different subjects that were not present in the reference probiotic <i>L. rhamnosus</i> strain ATCC 53103 (GG). Distinct genome signatures identified included the presence of a modified exopolysaccharide cluster, a characteristic confirmed in a further six clinical isolates. Additional features of LRHMDP2 and LRHMDP3 were altered transcriptional regulators from RpoN, NtrC, MutR, ArsR and zinc-binding Cro/CI families, as well as changes in the two-component sensor kinase response regulator and ABC transporters for ferric iron. Both clinical isolates of <i>L. rhamnosus</i> contained a single <i>Spa</i>FED cluster, as in <i>L. rhamnosus</i> Lc705, instead of the two <i>Spa</i> clusters (<i>Spa</i>CBA and <i>Spa</i>FED) identified in <i>L. rhamnosus</i> ATCC 53103 (GG). Genomic distance analysis and SNP divergence confirmed a close relationship of the clinical isolates but segregation from the reference probiotic <i>L. rhamnosus</i> strain ATCC 53103 (GG).</p></div

General Genome sequencing^a features and annotation^b features of <i>L. rhamnosus</i> clinical isolates and <i>L. rhamnosus</i> GG and <i>L. rhamnosus</i> Lc705 genomic features.

a<p>Using Roche GS(FLX+) pyrosequencing.</p>b<p>Based on results merged from the RAST (Rapid Annotation using Subsystem Technology) server and tRNAscan-SE.</p>c<p>assembled by Newbler Assembler 2.6.</p>d<p>Both <i>L.rhamnosus</i> clinical isolates (LRHMDP2 and LRHMDP3) were sourced from infected dental pulps from carious teeth categorised as representing the initial stages of infection of pulp tissue.</p>e<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090643#pone.0090643-Kankainen1" target="_blank">[13]</a>.</p