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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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Flow chart of the clustering analysis procedure for each value of compactness resolution parameter, α.The upper panel illustrates the k-split procedure within each cluster to detect optimal sub-clusters. The lower panel describes the compactness evaluation procedure (CEP) after k-split. CEP compares the parent cluster prior to k-split with the sub-clusters after k-split by means of the compactness measure, νl, and updates the partition accordingly. On the left, each step is illustrated by a graphical toy example. From the top, the pictures correspond to: the initial network subject to clustering, correct classification of boundary nodes by BDP (Before: before BDP, After: correction after BDP), identification of the optimal k via modularity Qk, final clusters, and comparison between initial network and sub-clusters via compactness. These steps are iterated for all clusters from the newly updated partition until no further update can be made.
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pcbi.1004574.g013: Flow chart of the clustering analysis procedure for each value of compactness resolution parameter, α.The upper panel illustrates the k-split procedure within each cluster to detect optimal sub-clusters. The lower panel describes the compactness evaluation procedure (CEP) after k-split. CEP compares the parent cluster prior to k-split with the sub-clusters after k-split by means of the compactness measure, νl, and updates the partition accordingly. On the left, each step is illustrated by a graphical toy example. From the top, the pictures correspond to: the initial network subject to clustering, correct classification of boundary nodes by BDP (Before: before BDP, After: correction after BDP), identification of the optimal k via modularity Qk, final clusters, and comparison between initial network and sub-clusters via compactness. These steps are iterated for all clusters from the newly updated partition until no further update can be made.

Mentions: The Eq (1) assigns a given node i to a new cluster in which the node i has the maximal number of interactions as determined by LPI. This boundary detection procedure (BDP) is iterated until there is no change in cluster membership, therefore leading to a stable partition. This process is illustrated in Fig 13 in the step “update boundary”, showing a toy example where misclassified red nodes in “Before” panel are correctly assigned in the “After” panel after BDP.


Multiscale Embedded Gene Co-expression Network Analysis.

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

Flow chart of the clustering analysis procedure for each value of compactness resolution parameter, α.The upper panel illustrates the k-split procedure within each cluster to detect optimal sub-clusters. The lower panel describes the compactness evaluation procedure (CEP) after k-split. CEP compares the parent cluster prior to k-split with the sub-clusters after k-split by means of the compactness measure, νl, and updates the partition accordingly. On the left, each step is illustrated by a graphical toy example. From the top, the pictures correspond to: the initial network subject to clustering, correct classification of boundary nodes by BDP (Before: before BDP, After: correction after BDP), identification of the optimal k via modularity Qk, final clusters, and comparison between initial network and sub-clusters via compactness. These steps are iterated for all clusters from the newly updated partition until no further update can be made.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi.1004574.g013: Flow chart of the clustering analysis procedure for each value of compactness resolution parameter, α.The upper panel illustrates the k-split procedure within each cluster to detect optimal sub-clusters. The lower panel describes the compactness evaluation procedure (CEP) after k-split. CEP compares the parent cluster prior to k-split with the sub-clusters after k-split by means of the compactness measure, νl, and updates the partition accordingly. On the left, each step is illustrated by a graphical toy example. From the top, the pictures correspond to: the initial network subject to clustering, correct classification of boundary nodes by BDP (Before: before BDP, After: correction after BDP), identification of the optimal k via modularity Qk, final clusters, and comparison between initial network and sub-clusters via compactness. These steps are iterated for all clusters from the newly updated partition until no further update can be made.
Mentions: The Eq (1) assigns a given node i to a new cluster in which the node i has the maximal number of interactions as determined by LPI. This boundary detection procedure (BDP) is iterated until there is no change in cluster membership, therefore leading to a stable partition. This process is illustrated in Fig 13 in the step “update boundary”, showing a toy example where misclassified red nodes in “Before” panel are correctly assigned in the “After” panel after BDP.

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