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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 Artif+Intell+Med
2014 ; 61
(2
): 63-78
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An extensive analysis of disease-gene associations using network integration and
fast kernel-based gene prioritization methods
#MMPMID24726035
Valentini G
; Paccanaro A
; Caniza H
; Romero AE
; Re M
Artif Intell Med
2014[Jun]; 61
(2
): 63-78
PMID24726035
show ga
OBJECTIVE: In the context of "network medicine", gene prioritization methods
represent one of the main tools to discover candidate disease genes by exploiting
the large amount of data covering different types of functional relationships
between genes. Several works proposed to integrate multiple sources of data to
improve disease gene prioritization, but to our knowledge no systematic studies
focused on the quantitative evaluation of the impact of network integration on
gene prioritization. In this paper, we aim at providing an extensive analysis of
gene-disease associations not limited to genetic disorders, and a systematic
comparison of different network integration methods for gene prioritization.
MATERIALS AND METHODS: We collected nine different functional networks
representing different functional relationships between genes, and we combined
them through both unweighted and weighted network integration methods. We then
prioritized genes with respect to each of the considered 708 medical subject
headings (MeSH) diseases by applying classical guilt-by-association, random walk
and random walk with restart algorithms, and the recently proposed kernelized
score functions. RESULTS: The results obtained with classical random walk
algorithms and the best single network achieved an average area under the curve
(AUC) across the 708 MeSH diseases of about 0.82, while kernelized score
functions and network integration boosted the average AUC to about 0.89. Weighted
integration, by exploiting the different "informativeness" embedded in different
functional networks, outperforms unweighted integration at 0.01 significance
level, according to the Wilcoxon signed rank sum test. For each MeSH disease we
provide the top-ranked unannotated candidate genes, available for further
bio-medical investigation. CONCLUSIONS: Network integration is necessary to boost
the performances of gene prioritization methods. Moreover the methods based on
kernelized score functions can further enhance disease gene ranking results, by
adopting both local and global learning strategies, able to exploit the overall
topology of the network.