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Genome-Wide Detection and Analysis of Multifunctional Genes.

Pritykin Y, Ghersi D, Singh M - PLoS Comput. Biol. (2015)

Bottom Line: We leverage functional genomics data sets for three organisms--H. sapiens, D. melanogaster, and S. cerevisiae--and show that, as compared to other annotated genes, genes involved in multiple biological processes possess distinct physicochemical properties, are more broadly expressed, tend to be more central in protein interaction networks, tend to be more evolutionarily conserved, and are more likely to be essential.We also find that multifunctional genes are significantly more likely to be involved in human disorders.Our analysis uncovers key features about multifunctional genes, and is a step towards a better genome-wide understanding of gene multifunctionality.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, Princeton University, Princeton, New Jersey, United States of America; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.

ABSTRACT
Many genes can play a role in multiple biological processes or molecular functions. Identifying multifunctional genes at the genome-wide level and studying their properties can shed light upon the complexity of molecular events that underpin cellular functioning, thereby leading to a better understanding of the functional landscape of the cell. However, to date, genome-wide analysis of multifunctional genes (and the proteins they encode) has been limited. Here we introduce a computational approach that uses known functional annotations to extract genes playing a role in at least two distinct biological processes. We leverage functional genomics data sets for three organisms--H. sapiens, D. melanogaster, and S. cerevisiae--and show that, as compared to other annotated genes, genes involved in multiple biological processes possess distinct physicochemical properties, are more broadly expressed, tend to be more central in protein interaction networks, tend to be more evolutionarily conserved, and are more likely to be essential. We also find that multifunctional genes are significantly more likely to be involved in human disorders. These same features also hold when multifunctionality is defined with respect to molecular functions instead of biological processes. Our analysis uncovers key features about multifunctional genes, and is a step towards a better genome-wide understanding of gene multifunctionality.

No MeSH data available.


Multifunctional genes are more broadly expressed.Boxplots of the number of organism parts and/or conditions in which multifunctional and other annotated genes are expressed are shown for (A) fly (microarray expression data from FlyAtlas and RNA-seq expression data from modENCODE) and (B) human (GNF atlas and eGenetics expression data obtained from Ensembl). Colored dots show the means, notches show bootstrap-generated 95% confidence intervals around the medians, boxes show quartile ranges, and whiskers extend to the most extreme data points within 1.5 times the size of the inner quartile range. Multifunctional genes are expressed in a significantly larger number of conditions than other annotated genes (Mann–Whitney U test).
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pcbi.1004467.g003: Multifunctional genes are more broadly expressed.Boxplots of the number of organism parts and/or conditions in which multifunctional and other annotated genes are expressed are shown for (A) fly (microarray expression data from FlyAtlas and RNA-seq expression data from modENCODE) and (B) human (GNF atlas and eGenetics expression data obtained from Ensembl). Colored dots show the means, notches show bootstrap-generated 95% confidence intervals around the medians, boxes show quartile ranges, and whiskers extend to the most extreme data points within 1.5 times the size of the inner quartile range. Multifunctional genes are expressed in a significantly larger number of conditions than other annotated genes (Mann–Whitney U test).

Mentions: Differential gene expression is evident across tissues and cell types. A gene expressed in different contexts may have different functions depending upon how and when it is expressed. Therefore, we hypothesized that a gene associated with multiple distinct functions may be expressed in a larger number of contexts. In order to assess the relationship between gene expression and gene multifunctionality, we use genome-wide mRNA expression data and count in how many conditions, tissues or cell types each gene is expressed. For fly, we use two datasets: (1) FlyAtlas [28], the Drosophila microarray gene expression atlas across different tissues in larva and adult, and (2) RNA-seq data from modENCODE across many different tissues and development time points, as aggregated by FlyBase [29, 30]. For human, we use information about organism parts in which genes are expressed, obtained from Ensembl BioMart [31]. We observe that in both human and fly, multifunctional genes are expressed more broadly than other annotated genes; that is, they are expressed in a significantly larger number of tissues or organism parts (p-values from 7e-38 to 2e-4, Mann–Whitney U test; Fig 3A and 3B).


Genome-Wide Detection and Analysis of Multifunctional Genes.

Pritykin Y, Ghersi D, Singh M - PLoS Comput. Biol. (2015)

Multifunctional genes are more broadly expressed.Boxplots of the number of organism parts and/or conditions in which multifunctional and other annotated genes are expressed are shown for (A) fly (microarray expression data from FlyAtlas and RNA-seq expression data from modENCODE) and (B) human (GNF atlas and eGenetics expression data obtained from Ensembl). Colored dots show the means, notches show bootstrap-generated 95% confidence intervals around the medians, boxes show quartile ranges, and whiskers extend to the most extreme data points within 1.5 times the size of the inner quartile range. Multifunctional genes are expressed in a significantly larger number of conditions than other annotated genes (Mann–Whitney U test).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4593560&req=5

pcbi.1004467.g003: Multifunctional genes are more broadly expressed.Boxplots of the number of organism parts and/or conditions in which multifunctional and other annotated genes are expressed are shown for (A) fly (microarray expression data from FlyAtlas and RNA-seq expression data from modENCODE) and (B) human (GNF atlas and eGenetics expression data obtained from Ensembl). Colored dots show the means, notches show bootstrap-generated 95% confidence intervals around the medians, boxes show quartile ranges, and whiskers extend to the most extreme data points within 1.5 times the size of the inner quartile range. Multifunctional genes are expressed in a significantly larger number of conditions than other annotated genes (Mann–Whitney U test).
Mentions: Differential gene expression is evident across tissues and cell types. A gene expressed in different contexts may have different functions depending upon how and when it is expressed. Therefore, we hypothesized that a gene associated with multiple distinct functions may be expressed in a larger number of contexts. In order to assess the relationship between gene expression and gene multifunctionality, we use genome-wide mRNA expression data and count in how many conditions, tissues or cell types each gene is expressed. For fly, we use two datasets: (1) FlyAtlas [28], the Drosophila microarray gene expression atlas across different tissues in larva and adult, and (2) RNA-seq data from modENCODE across many different tissues and development time points, as aggregated by FlyBase [29, 30]. For human, we use information about organism parts in which genes are expressed, obtained from Ensembl BioMart [31]. We observe that in both human and fly, multifunctional genes are expressed more broadly than other annotated genes; that is, they are expressed in a significantly larger number of tissues or organism parts (p-values from 7e-38 to 2e-4, Mann–Whitney U test; Fig 3A and 3B).

Bottom Line: We leverage functional genomics data sets for three organisms--H. sapiens, D. melanogaster, and S. cerevisiae--and show that, as compared to other annotated genes, genes involved in multiple biological processes possess distinct physicochemical properties, are more broadly expressed, tend to be more central in protein interaction networks, tend to be more evolutionarily conserved, and are more likely to be essential.We also find that multifunctional genes are significantly more likely to be involved in human disorders.Our analysis uncovers key features about multifunctional genes, and is a step towards a better genome-wide understanding of gene multifunctionality.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, Princeton University, Princeton, New Jersey, United States of America; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.

ABSTRACT
Many genes can play a role in multiple biological processes or molecular functions. Identifying multifunctional genes at the genome-wide level and studying their properties can shed light upon the complexity of molecular events that underpin cellular functioning, thereby leading to a better understanding of the functional landscape of the cell. However, to date, genome-wide analysis of multifunctional genes (and the proteins they encode) has been limited. Here we introduce a computational approach that uses known functional annotations to extract genes playing a role in at least two distinct biological processes. We leverage functional genomics data sets for three organisms--H. sapiens, D. melanogaster, and S. cerevisiae--and show that, as compared to other annotated genes, genes involved in multiple biological processes possess distinct physicochemical properties, are more broadly expressed, tend to be more central in protein interaction networks, tend to be more evolutionarily conserved, and are more likely to be essential. We also find that multifunctional genes are significantly more likely to be involved in human disorders. These same features also hold when multifunctionality is defined with respect to molecular functions instead of biological processes. Our analysis uncovers key features about multifunctional genes, and is a step towards a better genome-wide understanding of gene multifunctionality.

No MeSH data available.