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Table 1.

The number of cancer samples remaining after preprocessing.

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Fig 1.

Flowchart detailing the construction of an individual-specific miRNA-lncRNA network (ISMLN).

(A) Construction of the reference miRNA-lncRNA network. After selecting n non-tumor samples as the reference samples and 155653 miRNA-lncRNA associations as the basic edges, the reference network is constructed by computing the Pearson Correlation Coefficients (PCCs) based on miRNA and lncRNA expression data. (B) After the addition of the n+1th sample, which is a tumor sample, to the reference network, a perturbed miRNA-lncRNA network is built by calculating the PCCs. The difference between the above two miRNA-lncRNA networks is regarded as the individual-specific miRNA-lncRNA network (ISMLN).

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Fig 2.

The BMLN for each type of cancer.

Taking BRCA as an example, we obtained 508 ISMLNs. We then counted the number of samples with significant changes for each miRNA-lncRNA pair and calculated the significance score. For example, the miR-200a-XIST interaction was significantly altered in all 508 samples, so the corresponding significance score was 508/508 = 1. Similarly, the significance scores of all 155653 miRNA-lncRNA pairs were calculated. We then ranked the miRNA-lncRNA pairs in descending order based on their significance scores. Finally, we chose only the miRNA-lncRNA interactions with high scores for further analysis.

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Fig 3.

Entire flowchart.

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Fig 4.

The distribution of ΔPCC values.

The cutoff of significant ΔPCC are X = 0.332 and X = -0.332, respectively. The red curve is the normal distribution curve of ΔPCC.

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Fig 5.

ROC of distinct features.

A-F show the ROC curves of classification results that take the top 1, 2, 3, 4, or 5 and last 5 potential miRNA-lncRNA edge biomarkers and the differentially expressed RNAs as the features, respectively.

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Table 2.

The AUC of distinct features of node biomarkers and edge biomarkers.

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Table 2 Expand

Fig 6.

Volcano plots of potential miRNA and lncRNA edge biomarkers.

(A) Volcano plot of potential miRNA edge biomarkers. (B) Volcano plot of potential lncRNA edge biomarkers. Green nodes represent RNAs that are not differentially expressed, red nodes represent RNAs that are downregulated, and blue nodes represent RNAs that are upregulated.

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Fig 7.

Activity Scores of candidate edge biomarker miRNAs.

(A) The top 50 Activity Scores of miRNAs participating in potential miRNA-lncRNA biomarkers in BMLN of BRCA. (B) The categories of top 50 miRNAs based on the Activity Score in BMLN of BRCA.

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Fig 8.

(A) A heat map of the top 200 miRNA-lncRNA interactions in the six types of cancers. Each column represents a cancer, and each row represents the significance score of the corresponding miRNA-lncRNA pair. The redder the color, the greater the significance score of the corresponding pair. (B) The distribution of lncRNA biomarkers involved in the top 200 edge biomarkers in distinct cancers.

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