LDAI-ISPS: LncRNA-Disease Associations Inference Based on Integrated Space Projection Scores

Int J Mol Sci. 2020 Feb 22;21(4):1508. doi: 10.3390/ijms21041508.

Abstract

Long non-coding RNAs (long ncRNAs, lncRNAs) of all kinds have been implicated in a range of cell developmental processes and diseases, while they are not translated into proteins. Inferring diseases associated lncRNAs by computational methods can be helpful to understand the pathogenesis of diseases, but those current computational methods still have not achieved remarkable predictive performance: such as the inaccurate construction of similarity networks and inadequate numbers of known lncRNA-disease associations. In this research, we proposed a lncRNA-disease associations inference based on integrated space projection scores (LDAI-ISPS) composed of the following key steps: changing the Boolean network of known lncRNA-disease associations into the weighted networks via combining all the global information (e.g., disease semantic similarities, lncRNA functional similarities, and known lncRNA-disease associations); obtaining the space projection scores via vector projections of the weighted networks to form the final prediction scores without biases. The leave-one-out cross validation (LOOCV) results showed that, compared with other methods, LDAI-ISPS had a higher accuracy with area-under-the-curve (AUC) value of 0.9154 for inferring diseases, with AUC value of 0.8865 for inferring new lncRNAs (whose associations related to diseases are unknown), with AUC value of 0.7518 for inferring isolated diseases (whose associations related to lncRNAs are unknown). A case study also confirmed the predictive performance of LDAI-ISPS as a helper for traditional biological experiments in inferring the potential LncRNA-disease associations and isolated diseases.

Keywords: computational prediction model; disease similarity; lncRNA similarity; space projection.

MeSH terms

  • Algorithms*
  • Alzheimer Disease / genetics
  • Computational Biology / methods*
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Genetic Association Studies / methods*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Models, Genetic*
  • Prostatic Neoplasms / genetics
  • RNA, Long Noncoding / genetics*
  • ROC Curve
  • Uterine Cervical Neoplasms / genetics

Substances

  • RNA, Long Noncoding