Fig. 6: Applications of DeconmiR in solid tumor to identify cancer biomarkers.

A Strategy used to construct a gold standard list of breast cancer differentially expressed miRNAs. Briefly, two separate lists of DEMs are derived by comparing breast cancer cell lines to normal breast epithelial cell from FANTOM5 and microRNAome projects, respectively. By taking the overlap of these two, a high-confidence set of breast cancer DEMs occurring in the epithelial compartment of the breast was obtained. B The sensitivity and specificity of three different DEM identification methods: unadjusted analysis, adjusted using DeconmiR-estimated cell-type fractions as independent covariates, and using SVA. C Identification of epithelial-specific smoking differentially expressed miRNAs and their relevance in lung cancer. Smoothed scatterplot of CellDMC t-statistics in epithelial cells (x-axis) versus those in immune cells (y-axis) derived from a cohort of 48 pairs of lung adenocarcinoma and non-malignant lung tissue. Pearson correlation coefficients and p-values were calculated. Green dashed lines indicate level of statistical significance (FDR < 0.05). Orange and green points mark the up- and downregulated smoking miRNAs derived from bronchial airway with smoking as the phenotype. Those passed statistical significance threshold were labeled. D Boxplots indicates the top-rank smoking related miR-183-3p and miR-139-5p in bronchial airway are also differentially expressed in normal and cancer samples (n = 48) The boxes are bounded by the 25 and 75 percentiles and the center represents the median. The whiskers extend from each edge of the box to indicate the 1.5× interquartile range (IQR). P-values are derived from two-sided Wilcoxon rank sum test. E Scatterplots of the average expression of smoking up- and downregulated miRNAs against cell fractions of epithelial and immune cell fractions. Pearson correlation coefficients and p-values were calculated. F Scatterplots of expression levels of the top-rank smoking-associated epithelial-specific miRNA miR-183-3p against the epithelial cell fraction (left panel) and total immune cell fraction (right panel) across the 559 LUAD samples from the TCGA. Pearson correlation coefficients and p-values were calculated. G Scatterplot of Spearman correlation coefficients (y-axis) between expression and epithelial fraction, as computed over the 559 TCGA LUAD samples, against the CellDMC t-statistics for predicted epithelial-specific miRNAs derived from GSE110907. Dashed lines indicate level of statistical significance (FDR < 0.05). P-value is from Fisher’s exact test on the miRNAs passing significance in each quadrant. H Average expression levels of cell-specific miRNAs derived with CellDMC from the GSE110907, in the normal-adjacent (n = 46) and LUAD (n = 513) samples from the TCGA. See (D) for boxplot definition. P-values are derived from two-sided Wilcoxon rank sum test. Source data are provided as a Source Data file.