The “classical” pan-secretome of <i>L. rhamnosus</i>.

<p>A flower-plot schematic representation depicts the main components of the SignalP-predicted <i>L. rhamnosus</i> pan-secretome (230 proteins). Shown are the number of core (103) and dispensable (127) proteins and the total numbers of classically secreted proteins per each genome (flower petals). Names of the <i>L. rhamnosus</i> genomes (strains) are indicated. All annotated secreted proteins are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102762#pone.0102762.s004" target="_blank">Table S2</a>.</p

The pan-genome of <i>L. rhamnosus</i>.

<p>A flower-plot schematic representation illustrates the number of predicted core (2,095) and dispensable (2,798) genes that together make up the <i>L. rhamnosus</i> pan-genome (4,893 loci). Shown in the flower petals are the numbers of loci per genome that are predicted to be either unique or ORFan-like (parenthesized). Names of the <i>L. rhamnosus</i> genomes (strains) are indicated. All annotated genes are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102762#pone.0102762.s003" target="_blank">Table S1</a>.</p

The pan-genome development plot of <i>L. rhamnosus</i>.

<p>Shown is the progression of the <i>L. rhamnosus</i> pan-genome as additional strain-genomes are included. Pan-genome development was calculated with R statistical programming language and using Heap’s Law (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102762#s4" target="_blank">Materials and Methods</a>).</p

Phylogenomic tree of <i>L. rhamnosus</i>.

<p>For establishing the evolutionary relationships among the <i>L. rhamnosus</i> genomes, unrooted genome phylogenies based on aligned gene content were generated using the neighbor-joining method as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102762#s4" target="_blank">Materials and Methods</a>. Identities of the <i>L. rhamnosus</i> genomes (strains) are indicated. Origin and source of strains are grouped by color as follows: gut (blue), mouth (green), lungs (magenta), and dairy (red).</p

Locus tags for functionally relevant surface-protein loci in the <i>L. rhamnosus</i> pan-genome.

<p>*Corresponding gene found in dispensable genome.</p><p>**Corresponding gene found in core genome.</p>1<p>ORF is non-concatenated sequence of two adjoining contigs.</p

Epigenetic analysis of sporadic and Lynch-associated ovarian cancers reveals histology-specific patterns of DNA methylation

<div><p>Diagnosis and treatment of epithelial ovarian cancer is challenging due to the poor understanding of the pathogenesis of the disease. Our aim was to investigate epigenetic mechanisms in ovarian tumorigenesis and, especially, whether tumors with different histological subtypes or hereditary background (Lynch syndrome) exhibit differential susceptibility to epigenetic inactivation of growth regulatory genes. Gene candidates for epigenetic regulation were identified from the literature and by expression profiling of ovarian and endometrial cancer cell lines treated with demethylating agents. Thirteen genes were chosen for methylation-specific multiplex ligation-dependent probe amplification assays on 104 (85 sporadic and 19 Lynch syndrome-associated) ovarian carcinomas. Increased methylation (i.e., hypermethylation) of variable degree was characteristic of ovarian carcinomas relative to the corresponding normal tissues, and hypermethylation was consistently more prominent in non-serous than serous tumors for individual genes and gene sets investigated. Lynch syndrome-associated clear cell carcinomas showed the highest frequencies of hypermethylation. Among endometrioid ovarian carcinomas, lower levels of promoter methylation of <i>RSK4</i>, <i>SPARC</i>, and <i>HOXA9</i> were significantly associated with higher tumor grade; thus, the methylation patterns showed a shift to the direction of high-grade serous tumors. In conclusion, we provide evidence of a frequent epigenetic inactivation of <i>RSK4</i>, <i>SPARC</i>, <i>PROM1</i>, <i>HOXA10</i>, <i>HOXA9</i>, <i>WT1-AS</i>, <i>SFRP2</i>, <i>SFRP5</i>, <i>OPCML</i>, and MIR34B in the development of non-serous ovarian carcinomas of Lynch and sporadic origin, as compared to serous tumors. Our findings shed light on the role of epigenetic mechanisms in ovarian tumorigenesis and identify potential targets for translational applications.</p></div

Mutation pattern in ERBB receptor family.

<p>Mutations in <i>ERBB2</i> (ENST00000269571) grouped into four hotspots (top). Samples (n = 29) with a mutated member of ERBB receptor family are presented in columns (below). In addition to a hotspot mutation, some samples displayed simultaneously a non-hotspot mutation in the same gene, thus all mutations are not shown in the figure. Recep_L = Receptor L domain; Furin-like = Furin-like cysteine rich region; GF_recep = Growth factor receptor domain; Pkinase_Tyr = Protein tyrosine kinase.</p

Overview of AI events in SBA.

<p>Frequency of gains and losses in 106 SBA samples.</p

Mutational landscape of the most significant genes in MSS SBAs.

<p>The figure includes the 25 highest-ranking genes in MSS tumors (n = 91) according to OncodriveFML, ranked by the <i>P</i>-value (right, red line at <i>P</i> = 0.05). Of these, <i>TP53</i>, <i>KRAS</i>, <i>APC</i>, <i>SOX9</i>, <i>SMAD4</i>, <i>BRAF</i>, and <i>ACVR2A</i> were significant also after correction for multiple testing. Different colors distinguish between the different types of mutations (in the middle). “Double hit” refers to two truncating mutations. The percentage of mutated tumors by gene are shown on the left. The upper bars represent the total number of both synonymous and non-synonymous mutations per tumor.</p

Clinicopathologic features of the patient cohort.

<p>Clinicopathologic features of the patient cohort.</p