Directed mammalian gene regulatory networks using expression and comparative genomic hybridization microarray data from radiation hybrids.
Meiotic mapping of quantitative trait loci regulating expression (eQTLs) has allowed the construction of gene networks. However, the limited mapping resolution of these studies has meant that genotype data are largely ignored, leading to undirected networks that fail to capture regulatory hierarchie...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-06-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC2690838?pdf=render |
| _version_ | 1811263137478868992 |
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| author | Sangtae Ahn Richard T Wang Christopher C Park Andy Lin Richard M Leahy Kenneth Lange Desmond J Smith |
| author_facet | Sangtae Ahn Richard T Wang Christopher C Park Andy Lin Richard M Leahy Kenneth Lange Desmond J Smith |
| author_sort | Sangtae Ahn |
| collection | DOAJ |
| description | Meiotic mapping of quantitative trait loci regulating expression (eQTLs) has allowed the construction of gene networks. However, the limited mapping resolution of these studies has meant that genotype data are largely ignored, leading to undirected networks that fail to capture regulatory hierarchies. Here we use high resolution mapping of copy number eQTLs (ceQTLs) in a mouse-hamster radiation hybrid (RH) panel to construct directed genetic networks in the mammalian cell. The RH network covering 20,145 mouse genes had significant overlap with, and similar topological structures to, existing biological networks. Upregulated edges in the RH network had significantly more overlap than downregulated. This suggests repressive relationships between genes are missed by existing approaches, perhaps because the corresponding proteins are not present in the cell at the same time and therefore unlikely to interact. Gene essentiality was positively correlated with connectivity and betweenness centrality in the RH network, strengthening the centrality-lethality principle in mammals. Consistent with their regulatory role, transcription factors had significantly more outgoing edges (regulating) than incoming (regulated) in the RH network, a feature hidden by conventional undirected networks. Directed RH genetic networks thus showed concordance with pre-existing networks while also yielding information inaccessible to current undirected approaches. |
| first_indexed | 2024-04-12T19:39:20Z |
| format | Article |
| id | doaj.art-fdfca47cfe294e2db74d8f40ee16d36e |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-04-12T19:39:20Z |
| publishDate | 2009-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-fdfca47cfe294e2db74d8f40ee16d36e2022-12-22T03:19:08ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582009-06-0156e100040710.1371/journal.pcbi.1000407Directed mammalian gene regulatory networks using expression and comparative genomic hybridization microarray data from radiation hybrids.Sangtae AhnRichard T WangChristopher C ParkAndy LinRichard M LeahyKenneth LangeDesmond J SmithMeiotic mapping of quantitative trait loci regulating expression (eQTLs) has allowed the construction of gene networks. However, the limited mapping resolution of these studies has meant that genotype data are largely ignored, leading to undirected networks that fail to capture regulatory hierarchies. Here we use high resolution mapping of copy number eQTLs (ceQTLs) in a mouse-hamster radiation hybrid (RH) panel to construct directed genetic networks in the mammalian cell. The RH network covering 20,145 mouse genes had significant overlap with, and similar topological structures to, existing biological networks. Upregulated edges in the RH network had significantly more overlap than downregulated. This suggests repressive relationships between genes are missed by existing approaches, perhaps because the corresponding proteins are not present in the cell at the same time and therefore unlikely to interact. Gene essentiality was positively correlated with connectivity and betweenness centrality in the RH network, strengthening the centrality-lethality principle in mammals. Consistent with their regulatory role, transcription factors had significantly more outgoing edges (regulating) than incoming (regulated) in the RH network, a feature hidden by conventional undirected networks. Directed RH genetic networks thus showed concordance with pre-existing networks while also yielding information inaccessible to current undirected approaches.http://europepmc.org/articles/PMC2690838?pdf=render |
| spellingShingle | Sangtae Ahn Richard T Wang Christopher C Park Andy Lin Richard M Leahy Kenneth Lange Desmond J Smith Directed mammalian gene regulatory networks using expression and comparative genomic hybridization microarray data from radiation hybrids. PLoS Computational Biology |
| title | Directed mammalian gene regulatory networks using expression and comparative genomic hybridization microarray data from radiation hybrids. |
| title_full | Directed mammalian gene regulatory networks using expression and comparative genomic hybridization microarray data from radiation hybrids. |
| title_fullStr | Directed mammalian gene regulatory networks using expression and comparative genomic hybridization microarray data from radiation hybrids. |
| title_full_unstemmed | Directed mammalian gene regulatory networks using expression and comparative genomic hybridization microarray data from radiation hybrids. |
| title_short | Directed mammalian gene regulatory networks using expression and comparative genomic hybridization microarray data from radiation hybrids. |
| title_sort | directed mammalian gene regulatory networks using expression and comparative genomic hybridization microarray data from radiation hybrids |
| url | http://europepmc.org/articles/PMC2690838?pdf=render |
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