Cancer Genetics and Epigenetics 2016, Vol.4, No.1, 1-10
8
Construct multiple-network
7 Alzheimer's disease-related gene expression datasets were downloaded from the Gene Expression Omnibus
(GEO) database (Edgar et al., 2002). We preprocessed each gene expression dataset by affy package (Gautier et al.,
2004) of Bioconductor package (Gentleman et al., 2004), respectively. Secondly, we mapped probes to genes in
each expression dataset, and averaged expression values of same genes. Thirdly, we calculated the variance of
gene expression in each expression profile dataset, retained genes with variance at top 75%. Fourthly, we
calculated the correlation coefficient of gene expression values of each gene-pair in each expression dataset using
the R software WGCNA package (Langfelder and Horvath, 2008), and remained gene-pairs with the person
correlation coefficient greater than 0.75 and p-value less than 0.01 Finally, we remained gene-pairs have same
co-expression directions at more than 3 expression datasets to construct multiple-network.
Co-expression network had been used to identify cell module and predict function of protein-coding genes (Luo et
al., 2007; Sharan et al., 2007; Wren, 2009). Biological processes and cellular regulatory networks are very
complex and involve many interactions between molecules (Luo et al., 2007), Co-expression network can analyze
correlation of expression of biological molecules and extract the relevant biological processes, and its node
represents a biomolecule, edges showing co-expression relationship. In our multiple co-express networks, node
contains protein-coding genes, ncRNAs and ion channel protein genes. Genes which have similar expression
patterns under different experimental conditions are more likely to have similar functions (Lee et al., 2004) or
participate in relevant biological pathways (Eisen et al., 1998). To reduce the noise present in the microarray, to
improve the accuracy of multiple co-expression networks, we used 7 gene expression datasets, remained
gene-pairs have same co-expression direction in at least 3 expression datasets to construct the multiple
co-expression network.
ncRNA function prediction
Hub-based approach is the most direct method of analysis node function, which is enrichment function of
functional annotation information of direct neighbor node to predict the function of the node. We used the DAVID
bioinformatics tool to analyze functions of neighbor genes of ncRNAs as ncRNA functions. In order to improve
the accuracy of prediction ncRNA functions, we only select ncRNAs with more than 10 co-expression
coding-gene. We further analysis these ncRNAs function, and explore the relationship between ion channel
protein genes and ncRNAs.
References
Bertone P., Stolc V., Royce T.E., Rozowsky J.S., Urban A.E., Zhu X., Rinn J.L., Tongprasit W., Samanta M., and Weissman S., 2004, Global identification of
human transcribed sequences with genome tiling arrays, Science, 306: 2242-2246
Mid:15539566
Bolton E.M., Tuzova A.V., Walsh A.L., Lynch T., and Perry A.S., 2014, Noncoding RNAs in prostate cancer: the long and the short of it, Clinical Cancer
Research, 20: 35-43
Mid:24146262
Congrains A., Kamide K., Oguro R., Yasuda O., Miyata K., Yamamoto E., Kawai T., Kusunoki H., Yamamoto H., and Takeya Y., 2012, Genetic variants at the
9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B, Atherosclerosis, 220: 449-455
PMid:22178423
Edgar R., Domrachev M., and Lash A.E., 2002, Gene Expression Omnibus: NCBI gene expression and hybridization array data repository, Nucleic acids
research, 30: 207-210
Mid:11752295 PMCid:PMC99122
Eisen M.B., Spellman P.T., Brown P.O., and Botstein D., 1998, Cluster analysis and display of genome-wide expression patterns, Proceedings of the National
Academy of Sciences, 95: 14863-14868
Mid:9843981 PMCid:PMC24541
Faghihi M.A., Modarresi F., Khalil A.M., Wood D.E., Sahagan B.G., Morgan T.E., Finch C.E., Laurent Iii G.S., Kenny P.J., and Wahlestedt C., 2008,
Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of β-secretase, Nature medicine, 14: 723-730
Mid:18587408 PMCid:PMC2826895
Flicek P., Amode M.R., Barrell D., Beal K., Brent S., Carvalho-Silva D., Clapham P., Coates G., Fairley S., and Fitzgerald S., 2011, Ensembl 2012, Nucleic
acids research: gkr991
PMCid:PMC3245178
