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The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8) (<jats:italic>p<\/jats:italic> \u2248 0), desmin (DES) (<jats:italic>p<\/jats:italic> = 2.71 \u00d7 10<jats:sup>-6<\/jats:sup>) and enolase 1 (ENO1) (<jats:italic>p<\/jats:italic> = 4.19 \u00d7 10<jats:sup>-5<\/jats:sup>)], while two novel hub genes [RNA binding motif protein 9 (RBM9) (<jats:italic>p<\/jats:italic> = 1.50 \u00d7 10<jats:sup>-4<\/jats:sup>) and ribosomal protein L30 (RPL30) (<jats:italic>p<\/jats:italic> = 1.50 \u00d7 10<jats:sup>-4<\/jats:sup>)] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO) based analysis of the colon cancer-specific gene network and the sub-network that consisted of three-way gene interactions suggested that tumourigenesis in colon cancer resulted from dysfunction in protein biosynthesis and categories associated with ribonucleoprotein complex which are well supported by multiple lines of experimental evidence.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This study demonstrated that IL8, DES and ENO1 act as the central elements in colon cancer susceptibility, and protein biosynthesis and the ribosome-associated function categories largely account for the colon cancer tumuorigenesis. Thus, the newly developed relevancy-based networking approach offers a powerful means to reverse-engineer the disease-specific network, a promising tool for systematic dissection of complex diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-2-72","type":"journal-article","created":{"date-parts":[[2008,8,12]],"date-time":"2008-08-12T06:13:11Z","timestamp":1218521591000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Constructing disease-specific gene networks using pair-wise relevance metric: Application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements"],"prefix":"10.1186","volume":"2","author":[{"given":"Wei","family":"Jiang","sequence":"first","affiliation":[]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[]},{"given":"Shaoqi","family":"Rao","sequence":"additional","affiliation":[]},{"given":"Lihong","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Lei","family":"Du","sequence":"additional","affiliation":[]},{"given":"Chuanxing","family":"Li","sequence":"additional","affiliation":[]},{"given":"Chao","family":"Wu","sequence":"additional","affiliation":[]},{"given":"Hongzhi","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Yadong","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Baofeng","family":"Yang","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2008,8,10]]},"reference":[{"issue":"1","key":"229_CR1","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1186\/1471-2105-8-370","volume":"8","author":"JG Zhang","year":"2007","unstructured":"Zhang JG, Deng HW: Gene selection for classification of microarray data based on the Bayes error. 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