A consensus multi-view multi-objective gene selection approach for improved sample classification

Abstract

Background: In the field of computational biology, analyzing complex data helps to extract relevant biological information. Sample classification of gene expression data is one such popular bio-data analysis technique. However, the presence of a large number of irrelevant/redundant genes in expression data makes a sample classification algorithm working inefficiently. Feature selection is one such high-dimensionality reduction technique that helps to maximize the effectiveness of any sample classification algorithm. Recent advances in biotechnology have improved the biological data to include multi-modal or multiple views. Different 'omics' resources capture various equally important biological properties of entities. However, most of the existing feature selection methodologies are biased towards considering only one out of multiple biological resources. Consequently, some crucial aspects of available biological knowledge may get ignored, which could further improve feature selection efficiency.

Results: In this present work, we have proposed a Consensus Multi-View Multi-objective Clustering-based feature selection algorithm called CMVMC. Three controlled genomic and proteomic resources like gene expression, Gene Ontology (GO), and protein-protein interaction network (PPIN) are utilized to build two independent views. The concept of multi-objective consensus clustering has been applied within our proposed gene selection method to satisfy both incorporated views. Gene expression data sets of Multiple tissues and Yeast from two different organisms (Homo Sapiens and Saccharomyces cerevisiae, respectively) are chosen for experimental purposes. As the end-product of CMVMC, a reduced set of relevant and non-redundant genes are found for each chosen data set. These genes finally participate in an effective sample classification.

Conclusions: The experimental study on chosen data sets shows that our proposed feature-selection method improves the sample classification accuracy and reduces the gene-space up to a significant level. In the case of Multiple Tissues data set, CMVMC reduces the number of genes (features) from 5565 to 41, with 92.73% of sample classification accuracy. For Yeast data set, the number of genes got reduced to 10 from 2884, with 95.84% sample classification accuracy. Two internal cluster validity indices - Silhouette and Davies-Bouldin (DB) and one external validity index Classification Accuracy (CA) are chosen for comparative study. Reported results are further validated through well-known biological significance test and visualization tool.

Keywords: Feature selection; Gene ontology (GO); Multi-objective optimization; Multi-view clustering; Protein protein interaction network; Sample classification.

Fig. 1

Two views developed based on multiple ‘omics’ data

Fig. 2

The flowchart of proposed CMVMC-based gene selection algorithm

Fig. 3

Structure of each parent clustering solution in proposed CMVMC

Fig. 4

Formation of consensus clusters of view 1 and view 2

Fig. 5

Cluster-profile plot for one random gene cluster from Multiple tissues (131 genes and 103 samples) and Yeast (180 genes and 17 samples) data set

Fig. 6

The comparative Silhouette and DB values for obtained sample clustering solutions for both data sets

Fig. 7

The comparative Classification Accuracy (CA) of samples by proposed and existing gene selection approaches