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Fig 1.

Workflow of our robust selection algorithm (RSA) and validation of the RSA using previously published datasets.

(A) Schematic displaying the overview of the RSA. The inputs are clinical data and miRNA expression data; the outcomes are candidate miRNAs correlated with either good or poor survival. (B) Validation of the RSA using previously published gene signatures correlated with survival outcomes. We applied RSA to breast cancer dataset in Martin et al. And looked at the overlap of genes correlated with good and poor survival computed by RSA and from their results. Heatmap of these overlapping genes was drawn displaying the high gene intensity in yellow and low gene intensity in blue.

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Fig 2.

Candidate miRNAs significantly correlated with survival across cancer types.

(A) Candidate miRNAs from RSA significantly (robust p-value < 0.01) correlated with good survival or poor survival in at least 3 cancer types. (B) MiRNA-disease survival network. The circles indicate the miRNAs strongly linked with patient survival across diverse cancer types. Left to right: miRNAs linked to prognosis in one cancer type, 2 cancer types, and 3 cancer types. White rectangles represent cancer types. Yellow rectangles represent miRNAs. The color of the edge between a miRNA and a cancer type, indicates whether the miRNA is correlated with good (blue) or poor (orange) prognosis in a cancer type.

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Fig 3.

Characterization of miRNAs found to be strong candidate markers of prognosis based on copy number variation and expression.

(A) Further characterization of the 5 strong candidate miRNAs in terms of copy number variation and expression. The GISTIC-identified copy number alterations at each of the chromosome loci for the miRNAs in different cancer types are displayed. The “GS” or “PS” inside each circle indicates the link with good (blue) or poor (orange) prognosis. (B) Expression in tumor and normal tissue for each of the strong candidate miRNA. For OVCA, the normal tissue data were not available.

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Fig 4.

miRNA-mRNA interaction networks for miR-487b, whose functions are conserved across cancer types.

miR-487b miRNA-mRNA interaction networks. mRNA networks that were positively (yellow) or inversely (blue) correlated with miR-487b in OVCA and involved in functions conserved across cancer types are shown.

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Fig 5.

miRNA-mRNA interaction networks for miR-24-1*, whose functions are conserved across cancer types.

(A) miR-24-1* miRNA-mRNA interaction networks. Networks of positively (yellow) and inversely (blue) correlated mRNA and associated functions in BRCA, in which miR-24-1* is correlated with poor survival. (B) Common functions associated with the miRNA-mRNA correlation networks when miR-24-1* is correlated with good survival in three different cancer types. The log of the beta values in KIRC is displayed.

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Fig 6.

miRNA-mRNA interaction networks for miR-15b, whose functions are conserved across cancer types.

(A) Inversely correlated miRNA-mRNA network in BRCA showing conserved functions across 4 cancer types. (B) Positively correlated miRNA-mRNA network in BRCA showing conserved functions across 4 cancer types.

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Fig 6 Expand