Differential co-expression network analysis with DCoNA reveals isomiR targeting aberrations in prostate cancer

使用 DCoNA 进行差异共表达网络分析揭示了 isomiR 靶向前列腺癌的异常

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作者:Anton Zhiyanov, Narek Engibaryan, Stepan Nersisyan, Maxim Shkurnikov, Alexander Tonevitsky

Results

We developed Differential Co-expression Network Analysis (DCoNA)-an open-source statistical tool that allows one to identify pair interactions, which correlation significantly changes between two conditions. Comparing DCoNA with the state-of-the-art analog, we showed that DCoNA is a faster, more accurate and less memory-consuming tool. We applied DCoNA to prostate mRNA/miRNA-seq data collected from The Cancer Genome Atlas (TCGA) and compared predicted regulatory interactions of miRNA isoforms (isomiRs) and their target mRNAs between normal and cancer samples. As a result, almost all highly expressed isomiRs lost negative correlation with their targets in prostate cancer samples compared to ones without the pathology. One exception to this trend was the canonical isomiR of hsa-miR-93-5p acquiring cancer-specific targets. Further analysis showed that cancer aggressiveness simultaneously increased with the expression level of this isomiR in both TCGA primary tumor samples and 153 blood plasma samples of P. Hertsen Moscow Oncology Research Institute patients' cohort analyzed by miRNA microarrays. Availability and implementation: Source code and documentation of DCoNA are available at https://github.com/zhiyanov/DCoNA.

Supplementary Information

Supplementary data are available at Bioinformatics online.

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