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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 BMC+Bioinformatics
2018 ; 19
(1
): 106
Nephropedia Template TP
gab.com Text
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A method combining a random forest-based technique with the modeling of linkage
disequilibrium through latent variables, to run multilocus genome-wide
association studies
#MMPMID29587628
Sinoquet C
BMC Bioinformatics
2018[Mar]; 19
(1
): 106
PMID29587628
show ga
BACKGROUND: Genome-wide association studies (GWASs) have been widely used to
discover the genetic basis of complex phenotypes. However, standard single-SNP
GWASs suffer from lack of power. In particular, they do not directly account for
linkage disequilibrium, that is the dependences between SNPs (Single Nucleotide
Polymorphisms). RESULTS: We present the comparative study of two multilocus GWAS
strategies, in the random forest-based framework. The first method, T-Trees, was
designed by Botta and collaborators (Botta et al., PLoS ONE 9(4):e93379, 2014).
We designed the other method, which is an innovative hybrid method combining
T-Trees with the modeling of linkage disequilibrium. Linkage disequilibrium is
modeled through a collection of tree-shaped Bayesian networks with latent
variables, following our former works (Mourad et al., BMC Bioinformatics
12(1):16, 2011). We compared the two methods, both on simulated and real data.
For dominant and additive genetic models, in either of the conditions simulated,
the hybrid approach always slightly performs better than T-Trees. We assessed
predictive powers through the standard ROC technique on 14 real datasets. For 10
of the 14 datasets analyzed, the already high predicted power observed for
T-Trees (0.910-0.946) can still be increased by up to 0.030. We also assessed
whether the distributions of SNPs' scores obtained from T-Trees and the hybrid
approach differed. Finally, we thoroughly analyzed the intersections of top 100
SNPs output by any two or the three methods amongst T-Trees, the hybrid approach,
and the single-SNP method. CONCLUSIONS: The sophistication of T-Trees through
finer linkage disequilibrium modeling is shown beneficial. The distributions of
SNPs' scores generated by T-Trees and the hybrid approach are shown statistically
different, which suggests complementary of the methods. In particular, for 12 of
the 14 real datasets, the distribution tail of highest SNPs' scores shows larger
values for the hybrid approach. Thus are pinpointed more interesting SNPs than by
T-Trees, to be provided as a short list of prioritized SNPs, for a further
analysis by biologists. Finally, among the 211 top 100 SNPs jointly detected by
the single-SNP method, T-Trees and the hybrid approach over the 14 datasets, we
identified 72 and 38 SNPs respectively present in the top25s and top10s for each
method.