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Although widely adopted in nutritional systems biology, these networks typically encompass a single category of functional interaction (<jats:italic>i.e<\/jats:italic>., metabolic, regulatory or signaling) or nutrient. Incorporating multiple nutrients and functional interaction categories under an integrated framework represents an informative approach for gaining system level insight on nutrient metabolism.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We constructed a multi-level PPI network starting from the interactions of 200 vitamin-related proteins. Its final size was 1,657 proteins, with 2,700 interactions. To characterize the role of the proteins we computed 6 centrality indices and applied model-based clustering. We detected a subgroup of 22 proteins that were highly central and significantly related to vitamin D. Immune system and cancer-related processes were strongly represented among these proteins. Clustering of the centralities revealed a degree of redundancy among the indices; a repeated analysis using subsets of the centralities performed well in identifying the original set of 22 most central proteins.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Hierarchical and model-based clustering revealed multi-centrality hubs in a vitamin PPI network and redundancies among the centrality indices. Vitamin D-related proteins were strongly represented among network hubs, highlighting the pervasive effects of this nutrient. Our integrated approach to network construction identified promiscuous transcription factors, cytokines and enzymes - primarily related to immune system and cancer processes - representing potential gatekeepers linking vitamin intake to disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-5-195","type":"journal-article","created":{"date-parts":[[2011,12,3]],"date-time":"2011-12-03T18:21:49Z","timestamp":1322936509000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Model-based clustering reveals vitamin D dependent multi-centrality hubs in a network of vitamin-related proteins"],"prefix":"10.1186","volume":"5","author":[{"given":"Thanh-Phuong","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Scotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa J","family":"Morine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corrado","family":"Priami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,12,2]]},"reference":[{"key":"832_CR1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s12263-008-0090-5","volume":"3","author":"B van Ommen","year":"2008","unstructured":"van Ommen B, Cavalieri D, Roche HM, Klein UI, Daniel H: The challenges for molecular nutrition research 4: the \"nutritional systems biology level\". 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