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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 involved in a significantly larger number of regulatory and genetic interactions.Boxplots of the number of regulatory and/or genetic interactions for multifunctional and other annotated genes are shown for (A) fly, (B) human, and (C) yeast. 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 involved in significantly more regulatory and genetic interactions (Mann–Whitney U test).
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pcbi.1004467.g005: Multifunctional genes are involved in a significantly larger number of regulatory and genetic interactions.Boxplots of the number of regulatory and/or genetic interactions for multifunctional and other annotated genes are shown for (A) fly, (B) human, and (C) yeast. 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 involved in significantly more regulatory and genetic interactions (Mann–Whitney U test).

Mentions: Genes responsible for multiple functions may require more complex regulatory programs to differentiate functions across multiple tissues or conditions. In order to study how regulated multifunctional genes are, we use regulatory interactions from high-throughput ChIP experiments [35–38]. For each gene, we count the number of transcription factor–target interactions this gene participates in as a target. In all three organisms, we observe that multifunctional genes are regulated by a significantly larger number of transcription factors than are other annotated genes (p-values from 3e-54 to 7e-4, Mann–Whitney U test; Fig 5).


Genome-Wide Detection and Analysis of Multifunctional Genes.

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

Multifunctional genes are involved in a significantly larger number of regulatory and genetic interactions.Boxplots of the number of regulatory and/or genetic interactions for multifunctional and other annotated genes are shown for (A) fly, (B) human, and (C) yeast. 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 involved in significantly more regulatory and genetic interactions (Mann–Whitney U test).
© Copyright Policy
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4593560&req=5

pcbi.1004467.g005: Multifunctional genes are involved in a significantly larger number of regulatory and genetic interactions.Boxplots of the number of regulatory and/or genetic interactions for multifunctional and other annotated genes are shown for (A) fly, (B) human, and (C) yeast. 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 involved in significantly more regulatory and genetic interactions (Mann–Whitney U test).
Mentions: Genes responsible for multiple functions may require more complex regulatory programs to differentiate functions across multiple tissues or conditions. In order to study how regulated multifunctional genes are, we use regulatory interactions from high-throughput ChIP experiments [35–38]. For each gene, we count the number of transcription factor–target interactions this gene participates in as a target. In all three organisms, we observe that multifunctional genes are regulated by a significantly larger number of transcription factors than are other annotated genes (p-values from 3e-54 to 7e-4, Mann–Whitney U test; Fig 5).

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.