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2015 ; 11
(12
): e1005689
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Integration Analysis of Three Omics Data Using Penalized Regression Methods: An
Application to Bladder Cancer
#MMPMID26646822
Pineda S
; Real FX
; Kogevinas M
; Carrato A
; Chanock SJ
; Malats N
; Van Steen K
PLoS Genet
2015[Dec]; 11
(12
): e1005689
PMID26646822
show ga
Omics data integration is becoming necessary to investigate the genomic
mechanisms involved in complex diseases. During the integration process, many
challenges arise such as data heterogeneity, the smaller number of individuals in
comparison to the number of parameters, multicollinearity, and interpretation and
validation of results due to their complexity and lack of knowledge about
biological processes. To overcome some of these issues, innovative statistical
approaches are being developed. In this work, we propose a permutation-based
method to concomitantly assess significance and correct by multiple testing with
the MaxT algorithm. This was applied with penalized regression methods (LASSO and
ENET) when exploring relationships between common genetic variants, DNA
methylation and gene expression measured in bladder tumor samples. The overall
analysis flow consisted of three steps: (1) SNPs/CpGs were selected per each gene
probe within 1Mb window upstream and downstream the gene; (2) LASSO and ENET were
applied to assess the association between each expression probe and the selected
SNPs/CpGs in three multivariable models (SNP, CPG, and Global models, the latter
integrating SNPs and CPGs); and (3) the significance of each model was assessed
using the permutation-based MaxT method. We identified 48 genes whose expression
levels were significantly associated with both SNPs and CPGs. Importantly, 36
(75%) of them were replicated in an independent data set (TCGA) and the
performance of the proposed method was checked with a simulation study. We
further support our results with a biological interpretation based on an
enrichment analysis. The approach we propose allows reducing computational time
and is flexible and easy to implement when analyzing several types of omics data.
Our results highlight the importance of integrating omics data by applying
appropriate statistical strategies to discover new insights into the complex
genetic mechanisms involved in disease conditions.