LMSM: A modular approach for identifying lncRNA related miRNA sponge modules in breast cancer

PLoS Comput Biol. 2020 Apr 23;16(4):e1007851. doi: 10.1371/journal.pcbi.1007851. eCollection 2020 Apr.

Abstract

Until now, existing methods for identifying lncRNA related miRNA sponge modules mainly rely on lncRNA related miRNA sponge interaction networks, which may not provide a full picture of miRNA sponging activities in biological conditions. Hence there is a strong need of new computational methods to identify lncRNA related miRNA sponge modules. In this work, we propose a framework, LMSM, to identify LncRNA related MiRNA Sponge Modules from heterogeneous data. To understand the miRNA sponging activities in biological conditions, LMSM uses gene expression data to evaluate the influence of the shared miRNAs on the clustered sponge lncRNAs and mRNAs. We have applied LMSM to the human breast cancer (BRCA) dataset from The Cancer Genome Atlas (TCGA). As a result, we have found that the majority of LMSM modules are significantly implicated in BRCA and most of them are BRCA subtype-specific. Most of the mediating miRNAs act as crosslinks across different LMSM modules, and all of LMSM modules are statistically significant. Multi-label classification analysis shows that the performance of LMSM modules is significantly higher than baseline's performance, indicating the biological meanings of LMSM modules in classifying BRCA subtypes. The consistent results suggest that LMSM is robust in identifying lncRNA related miRNA sponge modules. Moreover, LMSM can be used to predict miRNA targets. Finally, LMSM outperforms a graph clustering-based strategy in identifying BRCA-related modules. Altogether, our study shows that LMSM is a promising method to investigate modular regulatory mechanism of sponge lncRNAs from heterogeneous data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Cluster Analysis
  • Computational Biology / methods*
  • Databases, Genetic
  • Female
  • Gene Expression Profiling
  • Humans
  • MicroRNAs / analysis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA, Long Noncoding / analysis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding

Grants and funding

JZ was supported by the National Natural Science Foundation of China (Grant Number: 61702069, 61963001), the Applied Basic Research Foundation of Science and Technology of Yunnan Province (Grant Number: 2017FB099). LL and JL were supported by the Australian Research Council Discovery Grant (Grant Number: DP170101306). TX was supported by the National Natural Science Foundation of China (Grant Number: 61902372). WZ was supported by the Education Science Research Foundation of Yunnan Province (Grant Number: 2018JS416). NR was supported by the National Natural Science Foundation of China (Grant Number: 61872405, 61720106004). TDL was supported by NHMRC Grant (Grant Number: 1123042). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.