Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology
<p>Abstract</p> <p>Background</p> <p>In many protein-protein interaction (PPI) networks, densely connected hub proteins are more likely to be essential proteins. This is referred to as the "centrality-lethality rule", which indicates that the topological place...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-10-01
|
| Series: | BMC Bioinformatics |
| Online Access: | http://www.biomedcentral.com/1471-2105/11/505 |
| _version_ | 1831696009294512128 |
|---|---|
| author | Leong Hon Srihari Sriganesh Ng Hoong Ning Kang Nesvizhskii Alexey I |
| author_facet | Leong Hon Srihari Sriganesh Ng Hoong Ning Kang Nesvizhskii Alexey I |
| author_sort | Leong Hon |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>In many protein-protein interaction (PPI) networks, densely connected hub proteins are more likely to be essential proteins. This is referred to as the "centrality-lethality rule", which indicates that the topological placement of a protein in PPI network is connected with its biological essentiality. Though such connections are observed in many PPI networks, the underlying topological properties for these connections are not yet clearly understood. Some suggested putative connections are the involvement of essential proteins in the maintenance of overall network connections, or that they play a role in essential protein clusters. In this work, we have attempted to examine the placement of essential proteins and the network topology from a different perspective by determining the correlation of protein essentiality and reverse nearest neighbor topology (RNN).</p> <p>Results</p> <p>The RNN topology is a weighted directed graph derived from PPI network, and it is a natural representation of the topological dependences between proteins within the PPI network. Similar to the original PPI network, we have observed that essential proteins tend to be hub proteins in RNN topology. Additionally, essential genes are enriched in clusters containing many hub proteins in RNN topology (RNN protein clusters). Based on these two properties of essential genes in RNN topology, we have proposed a new measure; the <it>RNN cluster centrality</it>. Results from a variety of PPI networks demonstrate that <it>RNN cluster centrality </it>outperforms other centrality measures with regard to the proportion of selected proteins that are essential proteins. We also investigated the biological importance of RNN clusters.</p> <p>Conclusions</p> <p>This study reveals that <it>RNN cluster centrality </it>provides the best correlation of protein essentiality and placement of proteins in PPI network. Additionally, merged RNN clusters were found to be topologically important in that essential proteins are significantly enriched in RNN clusters, and biologically important because they play an important role in many Gene Ontology (GO) processes.</p> |
| first_indexed | 2024-12-20T13:04:59Z |
| format | Article |
| id | doaj.art-adc1f92a5513465eb32d27a0967d9002 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-20T13:04:59Z |
| publishDate | 2010-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-adc1f92a5513465eb32d27a0967d90022022-12-21T19:39:49ZengBMCBMC Bioinformatics1471-21052010-10-0111150510.1186/1471-2105-11-505Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topologyLeong HonSrihari SriganeshNg HoongNing KangNesvizhskii Alexey I<p>Abstract</p> <p>Background</p> <p>In many protein-protein interaction (PPI) networks, densely connected hub proteins are more likely to be essential proteins. This is referred to as the "centrality-lethality rule", which indicates that the topological placement of a protein in PPI network is connected with its biological essentiality. Though such connections are observed in many PPI networks, the underlying topological properties for these connections are not yet clearly understood. Some suggested putative connections are the involvement of essential proteins in the maintenance of overall network connections, or that they play a role in essential protein clusters. In this work, we have attempted to examine the placement of essential proteins and the network topology from a different perspective by determining the correlation of protein essentiality and reverse nearest neighbor topology (RNN).</p> <p>Results</p> <p>The RNN topology is a weighted directed graph derived from PPI network, and it is a natural representation of the topological dependences between proteins within the PPI network. Similar to the original PPI network, we have observed that essential proteins tend to be hub proteins in RNN topology. Additionally, essential genes are enriched in clusters containing many hub proteins in RNN topology (RNN protein clusters). Based on these two properties of essential genes in RNN topology, we have proposed a new measure; the <it>RNN cluster centrality</it>. Results from a variety of PPI networks demonstrate that <it>RNN cluster centrality </it>outperforms other centrality measures with regard to the proportion of selected proteins that are essential proteins. We also investigated the biological importance of RNN clusters.</p> <p>Conclusions</p> <p>This study reveals that <it>RNN cluster centrality </it>provides the best correlation of protein essentiality and placement of proteins in PPI network. Additionally, merged RNN clusters were found to be topologically important in that essential proteins are significantly enriched in RNN clusters, and biologically important because they play an important role in many Gene Ontology (GO) processes.</p>http://www.biomedcentral.com/1471-2105/11/505 |
| spellingShingle | Leong Hon Srihari Sriganesh Ng Hoong Ning Kang Nesvizhskii Alexey I Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology BMC Bioinformatics |
| title | Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology |
| title_full | Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology |
| title_fullStr | Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology |
| title_full_unstemmed | Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology |
| title_short | Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology |
| title_sort | examination of the relationship between essential genes in ppi network and hub proteins in reverse nearest neighbor topology |
| url | http://www.biomedcentral.com/1471-2105/11/505 |
| work_keys_str_mv | AT leonghon examinationoftherelationshipbetweenessentialgenesinppinetworkandhubproteinsinreversenearestneighbortopology AT sriharisriganesh examinationoftherelationshipbetweenessentialgenesinppinetworkandhubproteinsinreversenearestneighbortopology AT nghoong examinationoftherelationshipbetweenessentialgenesinppinetworkandhubproteinsinreversenearestneighbortopology AT ningkang examinationoftherelationshipbetweenessentialgenesinppinetworkandhubproteinsinreversenearestneighbortopology AT nesvizhskiialexeyi examinationoftherelationshipbetweenessentialgenesinppinetworkandhubproteinsinreversenearestneighbortopology |