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Comparison of Gene Coexpression Profiles and Construction of Conserved Gene Networks to Find Functional Modules.

Okamura Y, Obayashi T, Kinoshita K - PLoS ONE (2015)

Bottom Line: For this purpose, the similarities of gene expression patterns and gene sequences have been separately utilized, although the combined information will provide a better solution.Some of the tightly coupled genes (modules) showed clear functional enrichment, such as immune system and cell cycle, indicating that our method could identify functionally related genes without any prior knowledge.We also found a few functional modules without any annotations, which may be good candidates for novel functional modules.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Information Sciences, Tohoku University, Sendai, Miyagi, Japan.

ABSTRACT

Background: Computational approaches toward gene annotation are a formidable challenge, now that many genome sequences have been determined. Each gene has its own function, but complicated cellular functions are achieved by sets of genes. Therefore, sets of genes with strong functional relationships must be identified. For this purpose, the similarities of gene expression patterns and gene sequences have been separately utilized, although the combined information will provide a better solution.

Result & discussion: We propose a new method to find functional modules, by comparing gene coexpression profiles among species. A coexpression pattern is represented as a list of coexpressed genes with each guide gene. We compared two coexpression lists, one from a human guide gene and the other from a homologous mouse gene, and defined a measure to evaluate the similarity between the lists. Based on this coexpression similarity, we detected the highly conserved genes, and constructed human gene networks with conserved coexpression between human and mouse. Some of the tightly coupled genes (modules) showed clear functional enrichment, such as immune system and cell cycle, indicating that our method could identify functionally related genes without any prior knowledge. We also found a few functional modules without any annotations, which may be good candidates for novel functional modules. All of the comparisons are available at the http://v1.coxsimdb.info web database.

No MeSH data available.


Overview of the conservation calculation method.(A) Schematic explanation of the comparison method for the conserved gene lists. Prepare a gene list pair for an orthologous gene pair from human and mouse. Count the number of human genes (yellow highlighted genes) with corresponding genes in the top N genes, where green arrows mean corresponding gene pairs. When a human gene corresponds to multiple mouse genes, we counted one human gene. However, when a mouse gene corresponds to multiple human genes, we counted all of the human genes. (B) Conservation chart of (A). This chart illustrates the change in the number of corresponding genes against the parameter value, N. (C) An example of a conservation chart for the most conserved guide gene. (D) An example of a conservation chart with a typical shape. (E) An example of genes with a turning point.
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pone.0132039.g001: Overview of the conservation calculation method.(A) Schematic explanation of the comparison method for the conserved gene lists. Prepare a gene list pair for an orthologous gene pair from human and mouse. Count the number of human genes (yellow highlighted genes) with corresponding genes in the top N genes, where green arrows mean corresponding gene pairs. When a human gene corresponds to multiple mouse genes, we counted one human gene. However, when a mouse gene corresponds to multiple human genes, we counted all of the human genes. (B) Conservation chart of (A). This chart illustrates the change in the number of corresponding genes against the parameter value, N. (C) An example of a conservation chart for the most conserved guide gene. (D) An example of a conservation chart with a typical shape. (E) An example of genes with a turning point.

Mentions: We compared the gene lists of the corresponding (or homologous) gene pairs to evaluate the conservation of coexpression patterns and expression data from two species, human and mouse. For each human gene (referred to as the guide gene), a list of coexpressed genes was created by ordering the genes by the coexpression strength, and a corresponding list of mouse genes was constructed for each homologous gene to the guide gene. The coexpression conservation of a homologous gene pair was measured as the similarity in the lists for the top N genes (Fig 1A). When the human guide gene had multiple homologous mouse genes, we compared the coexpressed gene lists for each pair of homologous genes. Next, we drew a “conservation chart” based on the number of corresponding gene pairs in the most coexpressed N genes, as shown in Fig 1B. If the human and mouse coexpression lists are exactly equal, then the conservation chart should look like the blue dashed line in Fig 1B. If the coexpression lists are equal to Fig 1A, then the conservation chart looks like the red dashed line in Fig 1B. A conservation chart represents the degree of similarity in the coexpression lists and indicates where the similarity exists.


Comparison of Gene Coexpression Profiles and Construction of Conserved Gene Networks to Find Functional Modules.

Okamura Y, Obayashi T, Kinoshita K - PLoS ONE (2015)

Overview of the conservation calculation method.(A) Schematic explanation of the comparison method for the conserved gene lists. Prepare a gene list pair for an orthologous gene pair from human and mouse. Count the number of human genes (yellow highlighted genes) with corresponding genes in the top N genes, where green arrows mean corresponding gene pairs. When a human gene corresponds to multiple mouse genes, we counted one human gene. However, when a mouse gene corresponds to multiple human genes, we counted all of the human genes. (B) Conservation chart of (A). This chart illustrates the change in the number of corresponding genes against the parameter value, N. (C) An example of a conservation chart for the most conserved guide gene. (D) An example of a conservation chart with a typical shape. (E) An example of genes with a turning point.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493118&req=5

pone.0132039.g001: Overview of the conservation calculation method.(A) Schematic explanation of the comparison method for the conserved gene lists. Prepare a gene list pair for an orthologous gene pair from human and mouse. Count the number of human genes (yellow highlighted genes) with corresponding genes in the top N genes, where green arrows mean corresponding gene pairs. When a human gene corresponds to multiple mouse genes, we counted one human gene. However, when a mouse gene corresponds to multiple human genes, we counted all of the human genes. (B) Conservation chart of (A). This chart illustrates the change in the number of corresponding genes against the parameter value, N. (C) An example of a conservation chart for the most conserved guide gene. (D) An example of a conservation chart with a typical shape. (E) An example of genes with a turning point.
Mentions: We compared the gene lists of the corresponding (or homologous) gene pairs to evaluate the conservation of coexpression patterns and expression data from two species, human and mouse. For each human gene (referred to as the guide gene), a list of coexpressed genes was created by ordering the genes by the coexpression strength, and a corresponding list of mouse genes was constructed for each homologous gene to the guide gene. The coexpression conservation of a homologous gene pair was measured as the similarity in the lists for the top N genes (Fig 1A). When the human guide gene had multiple homologous mouse genes, we compared the coexpressed gene lists for each pair of homologous genes. Next, we drew a “conservation chart” based on the number of corresponding gene pairs in the most coexpressed N genes, as shown in Fig 1B. If the human and mouse coexpression lists are exactly equal, then the conservation chart should look like the blue dashed line in Fig 1B. If the coexpression lists are equal to Fig 1A, then the conservation chart looks like the red dashed line in Fig 1B. A conservation chart represents the degree of similarity in the coexpression lists and indicates where the similarity exists.

Bottom Line: For this purpose, the similarities of gene expression patterns and gene sequences have been separately utilized, although the combined information will provide a better solution.Some of the tightly coupled genes (modules) showed clear functional enrichment, such as immune system and cell cycle, indicating that our method could identify functionally related genes without any prior knowledge.We also found a few functional modules without any annotations, which may be good candidates for novel functional modules.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Information Sciences, Tohoku University, Sendai, Miyagi, Japan.

ABSTRACT

Background: Computational approaches toward gene annotation are a formidable challenge, now that many genome sequences have been determined. Each gene has its own function, but complicated cellular functions are achieved by sets of genes. Therefore, sets of genes with strong functional relationships must be identified. For this purpose, the similarities of gene expression patterns and gene sequences have been separately utilized, although the combined information will provide a better solution.

Result & discussion: We propose a new method to find functional modules, by comparing gene coexpression profiles among species. A coexpression pattern is represented as a list of coexpressed genes with each guide gene. We compared two coexpression lists, one from a human guide gene and the other from a homologous mouse gene, and defined a measure to evaluate the similarity between the lists. Based on this coexpression similarity, we detected the highly conserved genes, and constructed human gene networks with conserved coexpression between human and mouse. Some of the tightly coupled genes (modules) showed clear functional enrichment, such as immune system and cell cycle, indicating that our method could identify functionally related genes without any prior knowledge. We also found a few functional modules without any annotations, which may be good candidates for novel functional modules. All of the comparisons are available at the http://v1.coxsimdb.info web database.

No MeSH data available.