Abstract

To further improve the effect of gene modules identification, combining the Newman algorithm in community detection and K-means algorithm framework, a new method of gene module identification, GCNA-Kpca algorithm, was proposed. The core idea of the algorithm was to build a gene co-expression network (GCN) based on gene expression data firstly; Then the Newman algorithm was used to initially identify gene modules based on the topology of GCN, and the number of clusters and clustering centers were determined; Finally the number of clusters and clustering centers were input into the K-means algorithm framework, and the secondary clustering was performed based on the gene expression profile to obtain the final gene modules. The algorithm took into account the role of modularity in the clustering process, and could find the optimal membership module for each gene through multiple iterations. Experimental results showed that the algorithm proposed in this paper had the best performance in error rate, biological significance and CNN classification indicators (Precision, Recall and F-score). The gene module obtained by GCNA-Kpca was used for the task of key gene identification, and these key genes had the highest prognostic significance. Moreover, GCNA-Kpca algorithm was used to identify 10 key genes in hepatocellular carcinoma (HCC): CDC20, CCNB1, EIF4A3, H2AFX, NOP56, RFC4, NOP58, AURKA, PCNA, and FEN1. According to the validation, it was reasonable to speculate that these 10 key genes could be biomarkers for HCC. And NOP56 and NOP58 are key genes for HCC that we discovered for the first time.

Highlights

  • To further improve the effect of gene modules identification, combining the Newman algorithm in community detection and K-means algorithm framework, a new method of gene module identification, Gene Coexpression Network Analysis (GCNA)-Kpca algorithm, was proposed

  • It is worth noting that NOP56 and NOP58 are the HUB genes of hepatocellular carcinoma (HCC) that we discovered for the first time

  • The key gene identification results showed that all key genes identified by the GCNA-Kpca algorithm could be used as prognostic targets; And compared with the other four algorithms, the key genes obtained by this algorithm had the highest prognostic significance

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Summary

Introduction

To further improve the effect of gene modules identification, combining the Newman algorithm in community detection and K-means algorithm framework, a new method of gene module identification, GCNA-Kpca algorithm, was proposed. The algorithm took into account the role of modularity in the clustering process, and could find the optimal membership module for each gene through multiple iterations. The most commonly used algorithm in GCNA is Weighted Gene Co-expression Network Analysis (WGCNA)[3], which identifies gene modules based on the idea of hierarchical clustering and combines the two tasks of “GCN construction” and “gene module identification” in one process. This study sought to analyze a range of available HCC-related gene expression data sets by proposed algorithm, with the goal of identifying key gene module and genes for HCC treatment and diagnosis

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