Identifying Drug Resistant miRNAs using Entropy Based Ranking

Authors: Jayanta Kumar Pal, Shubhra Sankar Ray and Sankar K. Pal
jkp_it08@yahoo.com, shubhra@isical.ac.in, sankar@isical.ac.in
Abstract: MicroRNAs play an important role in controlling drug sensitivity and resistance in cancer. Identification of responsible miRNAs for drug resistance can enhance the effectiveness of treatment. A new set theoretic entropy measure (SPEM) is defined to determine the relevance and level of confidence of miRNAs in deciding their drug resistant nature. Here, a pattern is represented by a pair of values. One of them implies the degree of its belongingness (fuzzy membership) to a class and the other represents the actual class of origin (crisp membership). A measure, called granular probability, is defined that determines the confidence level of having a particular pair of membership values. The granules used to compute the said probability are formed by a histogram based method where each bin of a histogram is considered as one granule. The width and number of the bins are automatically determined by the algorithm. The set thus defined, comprising a pair of membership values and the confidence level for having them, is used for the computation of SPEM and thereby identifying the drug resistant miRNAs. The efficiency of SPEM is demonstrated extensively on six data sets. While the achieved $F$-score in classifying sensitive and resistant samples ranges between 0.31 & 0.50 using all the miRNAs by SVM classifier, the same score varies from 0.67 to 0.94 using only the top 1\% drug resistant miRNAs. Superiority of the proposed method as compared to some existing ones is established in terms of F-score. The significance of the top 1% miRNAs in corresponding cancer is also verified by the different articles based on biological investigations.
Data set: Colon (GEO: GSE30894), Esophageal (GEO: GSE50224), Lung (GEO: GSE51828), Overian (GEO: GSE43867), Squamous cell (GEO: GSE50224), Breast (GEO: GSE71142)
Software:
  1. Download the archives corresponding to, and data set (e.g. colon).
  2. Extract both the archives (zip file) and keep the extracted files in the same directory
  3. Run SPEM.m
  4. The program returns the name of the miRNAs and the miRNA ID nos. according to the order of the input miRNA expression values.
  5. If the name of the miRNAs are not provided (miRNA.txt file is missing), the program returns the miRNA ID nos. according to the order of the input miRNA expression values.
  6. The program also creats a file "sel.txt" which stores the name or the ID of the selected miRNAs.
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