LncRNAs associated with breast cancer stromal or immune cells.

<p>LncRNAs associated with breast cancer stromal or immune cells.</p

Stromal cell, immune cell and tumour purity measures for each cluster derived from UBCS and TCGA samples according to ESTIMATE [27].

<p>UBCS: A, stromal cell content. B, immune cell content. C, tumour purity. TCGA: D, stromal cell content. E, immune cell content. F, tumour purity.</p

Comparison between meta-genes driving clustering of UBSC and TCGA tumour samples.

<p>Comparison between meta-genes driving clustering of UBSC and TCGA tumour samples.</p

Correlation of immune response-associated lncRNAs with specific immune cell type.

<p>A, <i>RP11-1008C21</i>.<i>1</i>. B, <i>RP5-899E9</i>.<i>1</i>. C, <i>RP3-460G2</i>.<i>2</i>. Each box is generated from correlations obtained between each lncRNA and a set of established markers for the corresponding immune cell type. Red horizontal dashed line at <i>r</i> = 0.48 indicates significance at <i>p</i><0.0001. The macrophage cell type achieves median <i>r</i>>0.48 across all lncRNAs and is highlighted in green. Only immune cell types represented by >3 markers are shown on the boxplots.</p

Correlation between six potential lncRNA basal-like breast cancer markers and their neighbouring genes, and comparison of correlation across cancer types.

<p>Each segment of the figure consists of (1) a scatterplot comparing FPKM expression values of the lncRNA with the neighbouring PC gene of interest, and (2) a comparison of the rank achieved by Pearson correlation of the PC gene with the lncRNA between cancer types. A, <i>RP11-19E11</i>.<i>1</i> versus <i>EN1</i>. B, <i>LINC00393</i> versus <i>KLF5</i>. C, <i>CTD-2015G9</i>.<i>2</i> versus <i>FOXL1</i>. D, <i>RP11-10A14</i>.<i>5</i> versus <i>PPP1R3B</i>. E, <i>CTD-2527I21</i>.<i>15</i> versus <i>FXYD3</i>. F, <i>LINC01198</i> versus <i>LCP1</i>. Only cancer types in which lncRNA achieves expression ((mean FPKM+SD)>1.00) and variability (CV>0.10) thresholds were considered. Rank score = 1-(n/N) where n = position of PC gene in list of PC genes ranked in descending order of correlation to lncRNA, and N = total number of PC genes (17308). Rank score>~0.99 indicates PC gene ranked in top 200. Breast cancer is highlighted in red. TCGA cancer type codes are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163238#pone.0163238.s011" target="_blank">S8 Table</a>.</p

Application of non-negative matrix factorization (NMF) to optimal clustering of UBCS and TCGA lncRNA expression.

<p>A, consensus matrix at <i>k</i> = 4 for lncRNA expression across 63 UBCS samples. B, consensus matrix at <i>k</i> = 3 for lncRNA expression across 339 TCGA samples. C, contributing cancer types and mean consensus value of each UBCS cluster. D, contributing cancer types and mean consensus value of each TCGA cluster. “Representative” disease indicates the majority breast cancer subtype in the cluster, and numbers of models are given in brackets. Mean consensus value was computed from 200 runs of NMF.</p

Comparison of lncRNA basal-like marker expression between breast cancer intrinsic subtypes.

<p>A, <i>CTD-2015G9</i>.<i>2</i>. B, <i>CTD-2527I21</i>.<i>15</i>. C, <i>LINC00393</i>. D, <i>LINC01198</i>. E, <i>RP11-10A14</i>.<i>5</i>. F, <i>RP11-19E11</i>.<i>1</i>. Boxplots representing the basal-like subtype are highlighted in either red (UBCS) or blue (TCGA).</p

Association plots of the 44 typed SNPs and 434 imputed variants in the <i>CHEK1</i> region.

<p>The most significant signal (rs2155388, p=3.1x10^-5) is labelled with the large blue circle. The typed SNPs and the imputed variants are shown in the circle and diamond symbols, respectively. Pair-wise r² with rs2155388 were calculated in 85 CEU and 89 GBR (integrated call release as of 2010-11-23) in the 1000 genomes project. Gene transcripts are indicated by the dark green lines, with right arrowhead for the “+” strand and left arrowhead for the “-” strand. Recombination rate (blue line) was obtained from HapMap II.</p

Forest plots of the most significant <i>ATR</i> and <i>CHEK1</i> SNP associations.

<p>(A) the <i>ATR</i> rs6805118 associations. SEARCH: Studies of Epidemiology and Risk Factors in Cancer Heredity [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068578#B8" target="_blank">8</a>]; NHS II: Nurses’ Health Study (premenopausal women) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068578#B9" target="_blank">9</a>]; SBCS: Sheffield Breast Cancer Study (B) the <i>CHEK1</i> rs2155388 associations. UBCS: Utah Breast Cancer Study. For each panel, fixed effect estimate (pooled OR) is shown, with p value for homogeneity (the Cochran’s Q test, p_het) and I-squared for the amount of heterogeneity in parenthesis. DL pooled OR stands for the random effect model derived from the DerSimonian-Laird estimator.</p

Association plots of the 32 typed SNPs and 454 imputed variants in the <i>ATR</i> region.

<p>The most significant signal (rs6805118, p=7.6x10^-5) is labelled with the large blue circle. Circle symbols stand for the typed SNPs and diamond symbols represent the imputed variants. LD associations (r²) with rs6805118 were calculated in 85 CEU and 89 GBR (integrated call release as of 2010-11-23) in the 1000 genomes project. Gene transcripts are indicated by the dark green lines, with right arrowhead for the “+” strand and left arrowhead for the “-” strand. Recombination rate (blue line) was obtained from HapMap II.</p