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Subpathway-LNCE: Identify dysfunctional subpathways competitively regulated by lncRNAs through integrating
Xinrui Shi1, Yanjun Xu1, Chunlong Zhang1
1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Abstract:
Recently, studies have reported that long noncoding RNAs (lncRNAs) can act as modulators of mRNAs through competitively binding to microRNAs (miRNAs) and have relevance to tumorigenesis as well as other diseases. Identify lncRNA competitively regulated subpathway not only can gain insight into the initiation and progression of disease, but also help for understanding the functional roles of lncRNAs in the disease context. Here, we present an effective method, Subpathway-LNCE, which was specifically designed to identify lncRNAs competitively regulated functions and the functional roles of these competitive regulation lncRNAs have not be well characterized in diseases. Moreover, the method integrated lncRNA-mRNA expression profile and pathway topologies. Using prostate cancer datasets and LUAD data sets, we confirmed the effectiveness of our method in identifying disease associated dysfunctional subpathway that regulated by lncRNAs. By analyzing kidney renal clear cell carcinoma related lncRNA competitively regulated subpathway network, we show that Subpathway-LNCE can help uncover disease key lncRNAs. Furthermore, we demonstrated that our method is reproducible and robust. Subpathway-LNCE provide a flexible tool to identify lncRNA competitively regulated signal subpathways underlying certain condition, and help to expound the functional roles of lncRNAs in various status. Subpathway-LNCE has been developed as an R package freely available at https://cran.rstudio.com/web/packages/SubpathwayLNCE/.
Insights
This study introduces Subpathway-LNCE, a novel method to identify long noncoding RNAs (lncRNAs) that regulate disease pathways. This tool helps uncover the roles of lncRNAs in diseases like cancer.
Area of Science:
- Molecular Biology
- Bioinformatics
- Genomics
Background:
- Long noncoding RNAs (lncRNAs) are increasingly recognized as crucial regulators in various diseases, including cancer.
- lncRNAs can modulate messenger RNA (mRNA) stability and translation by competitively binding to microRNAs (miRNAs).
- Understanding lncRNA-mediated regulatory networks is vital for deciphering disease mechanisms and identifying therapeutic targets.
Purpose of the Study:
- To develop and validate an effective computational method, Subpathway-LNCE, for identifying lncRNA-competitively regulated subpathways.
- To elucidate the functional roles of lncRNAs in disease pathogenesis through pathway analysis.
- To provide a tool for uncovering disease-associated lncRNAs and their regulatory functions.
Main Methods:
- Integration of lncRNA-mRNA expression profiles with pathway topology data.
- Development of the Subpathway-LNCE algorithm to identify dysregulated subpathways driven by lncRNA-miRNA-mRNA interactions.
- Application and validation of the method using datasets from prostate cancer, lung adenocarcinoma (LUAD), and kidney renal clear cell carcinoma.
Main Results:
- Subpathway-LNCE successfully identified disease-associated dysfunctional subpathways regulated by lncRNAs in various cancer types.
- The method demonstrated effectiveness in pinpointing key lncRNAs involved in kidney renal clear cell carcinoma.
- The Subpathway-LNCE method was confirmed to be reproducible and robust across different datasets.
Conclusions:
- Subpathway-LNCE offers a flexible and powerful approach to identify lncRNA-regulated signal subpathways in specific disease contexts.
- The tool aids in understanding the functional significance of lncRNAs in disease progression and provides insights into potential therapeutic strategies.
- An R package for Subpathway-LNCE is publicly available, facilitating broader research applications.
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