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Multiscale Embedded Gene Co-expression Network Analysis.

Song WM, Zhang B - PLoS Comput. Biol. (2015)

Bottom Line: Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases.However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness.MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.

ABSTRACT
Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG) has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(/V/3), the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) by: i) introducing quality control of co-expression similarities, ii) parallelizing embedded network construction, and iii) developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs). We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA). MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

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Related in: MedlinePlus

Degree distributions of the BRCA PFN (A) and the LUAD PFN (B).The x-axis is the logarithm of degree k and the y-axis is the logarithm of inverse cumulative degree distribution, P(k’ > k). Red straight line is fitted distribution for P(k^'>k)~k^(γ+1), where γ is the estimated exponent of the underlying degree distribution. Respective γ value is displayed at the top.
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pcbi.1004574.g005: Degree distributions of the BRCA PFN (A) and the LUAD PFN (B).The x-axis is the logarithm of degree k and the y-axis is the logarithm of inverse cumulative degree distribution, P(k’ > k). Red straight line is fitted distribution for P(k^'>k)~k^(γ+1), where γ is the estimated exponent of the underlying degree distribution. Respective γ value is displayed at the top.

Mentions: As shown in Fig 5A, the BRCA PFN is scale-free by following a typical power-law degree distribution with exponent γ ≤ 3, consistent with the frequently observed range of exponents, i.e., 2 ≤ γ ≤ 3, in real-world complex networks [28]. However, the LUAD PFN does not exhibit the characteristics of scale-free degree distribution across all k though the distribution between 3 ≤ k ≤ 50 is scalefree (Fig 5B). The decaying tail at k ≥ 50 in the LUAD PFN shows the characteristics of exponential distributions. The diameters of the BRCA and LUAD PFNs are ~11.3, which is in accordance to the hallmark feature of small-world networks with diameters around log(/V/).


Multiscale Embedded Gene Co-expression Network Analysis.

Song WM, Zhang B - PLoS Comput. Biol. (2015)

Degree distributions of the BRCA PFN (A) and the LUAD PFN (B).The x-axis is the logarithm of degree k and the y-axis is the logarithm of inverse cumulative degree distribution, P(k’ > k). Red straight line is fitted distribution for P(k^'>k)~k^(γ+1), where γ is the estimated exponent of the underlying degree distribution. Respective γ value is displayed at the top.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664553&req=5

pcbi.1004574.g005: Degree distributions of the BRCA PFN (A) and the LUAD PFN (B).The x-axis is the logarithm of degree k and the y-axis is the logarithm of inverse cumulative degree distribution, P(k’ > k). Red straight line is fitted distribution for P(k^'>k)~k^(γ+1), where γ is the estimated exponent of the underlying degree distribution. Respective γ value is displayed at the top.
Mentions: As shown in Fig 5A, the BRCA PFN is scale-free by following a typical power-law degree distribution with exponent γ ≤ 3, consistent with the frequently observed range of exponents, i.e., 2 ≤ γ ≤ 3, in real-world complex networks [28]. However, the LUAD PFN does not exhibit the characteristics of scale-free degree distribution across all k though the distribution between 3 ≤ k ≤ 50 is scalefree (Fig 5B). The decaying tail at k ≥ 50 in the LUAD PFN shows the characteristics of exponential distributions. The diameters of the BRCA and LUAD PFNs are ~11.3, which is in accordance to the hallmark feature of small-world networks with diameters around log(/V/).

Bottom Line: Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases.However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness.MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.

ABSTRACT
Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG) has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(/V/3), the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) by: i) introducing quality control of co-expression similarities, ii) parallelizing embedded network construction, and iii) developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs). We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA). MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

Show MeSH
Related in: MedlinePlus