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2014 ; 15
(ä): 153
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Improving the sensitivity of sample clustering by leveraging gene co-expression
networks in variable selection
#MMPMID24885641
Wang Z
; San Lucas FA
; Qiu P
; Liu Y
BMC Bioinformatics
2014[May]; 15
(ä): 153
PMID24885641
show ga
BACKGROUND: Many variable selection techniques have been proposed for the
clustering of gene expression data. While these methods tend to filter out
irrelevant genes and identify informative genes that contribute to a clustering
solution, they are based on criteria that do not consider the potential
interactive influence among individual genes. Motivated by ensemble clustering,
there is a strong interest in leveraging the structure of gene networks for gene
selection, so that the relationship information between genes can be effectively
utilized, while the selected genes are expected to preserve all the possible
clustering structures in the data. RESULTS: We present a new filter method that
uses the gene connectivity in the gene co-expression network as the evaluation
criteria for variable selection. The gene connectivity measures the importance of
the genes in term of their expression similarity with others in the co-expression
network. The hard threshold and soft threshold transformations are employed to
construct the gene co-expression networks. Both simulation studies and real data
analysis have shown that the network based on soft thresholding is more effective
in selecting relevant variables and provides better clustering results compared
to the hard thresholding transformation and two other canonical filter methods
for variable selection. Furthermore, a new module analysis approach is proposed
to reveal the higher order organization of the gene space, where the genes of a
module share significant topological similarity and are associated with a
consensus partition of the sample space. We demonstrate that the identified
modules can lead to biologically meaningful sample partitions that might be
missed by other methods. CONCLUSIONS: By leveraging the structure of gene
co-expression network, first we propose a variable selection method that selects
individual genes with top connectivity. Both simulation studies and real data
application have demonstrated that our method has better performance in terms of
the reliability of the selected genes and sample clustering results. In addition,
we propose a module recovery method that can help discover novel sample
partitions that might be hidden when performing clustering analyses using all
available genes. The source code of our program is available at
http://nba.uth.tmc.edu/homepage/liu/netVar/.