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Multi-level reproducibility of signature hubs in human interactome for breast cancer metastasis
BACKGROUND: It has been suggested that, in the human protein-protein interaction network, changes of co-expression between highly connected proteins ("hub") and their interaction neighbours might have important roles in cancer metastasis and be predictive disease signatures for patient out...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990745/ https://www.ncbi.nlm.nih.gov/pubmed/21059271 http://dx.doi.org/10.1186/1752-0509-4-151 |
_version_ | 1782192508571222016 |
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author | Yao, Chen Li, Hongdong Zhou, Chenggui Zhang, Lin Zou, Jinfeng Guo, Zheng |
author_facet | Yao, Chen Li, Hongdong Zhou, Chenggui Zhang, Lin Zou, Jinfeng Guo, Zheng |
author_sort | Yao, Chen |
collection | PubMed |
description | BACKGROUND: It has been suggested that, in the human protein-protein interaction network, changes of co-expression between highly connected proteins ("hub") and their interaction neighbours might have important roles in cancer metastasis and be predictive disease signatures for patient outcome. However, for a cancer, such disease signatures identified from different studies have little overlap. RESULTS: Here, we propose a systemic approach to evaluate the reproducibility of disease signatures at multiple levels, on the basis of some statistically testable biological models. Using two datasets for breast cancer metastasis, we showed that different signature hubs identified from different studies were highly consistent in terms of significantly sharing interaction neighbours and displaying consistent co-expression changes with their overlapping neighbours, whereas the shared interaction neighbours were significantly over-represented with known cancer genes and enriched in pathways deregulated in breast cancer pathogenesis. Then, we showed that the signature hubs identified from the two datasets were highly reproducible at the protein interaction and pathway levels in three other independent datasets. CONCLUSIONS: Our results provide a possible biological model that different signature hubs altered in different patient cohorts could disturb the same pathways associated with cancer metastasis through their interaction neighbours. |
format | Text |
id | pubmed-2990745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29907452010-12-13 Multi-level reproducibility of signature hubs in human interactome for breast cancer metastasis Yao, Chen Li, Hongdong Zhou, Chenggui Zhang, Lin Zou, Jinfeng Guo, Zheng BMC Syst Biol Research Article BACKGROUND: It has been suggested that, in the human protein-protein interaction network, changes of co-expression between highly connected proteins ("hub") and their interaction neighbours might have important roles in cancer metastasis and be predictive disease signatures for patient outcome. However, for a cancer, such disease signatures identified from different studies have little overlap. RESULTS: Here, we propose a systemic approach to evaluate the reproducibility of disease signatures at multiple levels, on the basis of some statistically testable biological models. Using two datasets for breast cancer metastasis, we showed that different signature hubs identified from different studies were highly consistent in terms of significantly sharing interaction neighbours and displaying consistent co-expression changes with their overlapping neighbours, whereas the shared interaction neighbours were significantly over-represented with known cancer genes and enriched in pathways deregulated in breast cancer pathogenesis. Then, we showed that the signature hubs identified from the two datasets were highly reproducible at the protein interaction and pathway levels in three other independent datasets. CONCLUSIONS: Our results provide a possible biological model that different signature hubs altered in different patient cohorts could disturb the same pathways associated with cancer metastasis through their interaction neighbours. BioMed Central 2010-11-09 /pmc/articles/PMC2990745/ /pubmed/21059271 http://dx.doi.org/10.1186/1752-0509-4-151 Text en Copyright ©2010 Yao et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yao, Chen Li, Hongdong Zhou, Chenggui Zhang, Lin Zou, Jinfeng Guo, Zheng Multi-level reproducibility of signature hubs in human interactome for breast cancer metastasis |
title | Multi-level reproducibility of signature hubs in human interactome for breast cancer metastasis |
title_full | Multi-level reproducibility of signature hubs in human interactome for breast cancer metastasis |
title_fullStr | Multi-level reproducibility of signature hubs in human interactome for breast cancer metastasis |
title_full_unstemmed | Multi-level reproducibility of signature hubs in human interactome for breast cancer metastasis |
title_short | Multi-level reproducibility of signature hubs in human interactome for breast cancer metastasis |
title_sort | multi-level reproducibility of signature hubs in human interactome for breast cancer metastasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990745/ https://www.ncbi.nlm.nih.gov/pubmed/21059271 http://dx.doi.org/10.1186/1752-0509-4-151 |
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