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Thyrotropin releasing hormone is synthesized in the hypothalamus and regulates thyrotropin stimulating hormone gene expression in the pituitary gland. In order to understand the complexity of the thyroid pathways, and using experimental data retrieved from the biomedical literature (e.g., NCBI, HuGE Navigator, Protein Data Bank, and KEGG), we constructed a metabolic map of the thyroid hormone pathway at a molecular level and analyzed it topologically. A total of five hub nodes were predicted in regards to the transcription thyroid receptor (TR), cAMP response element-binding protein (CREB), signal transducer and activator of transcription 3 (STAT 3), nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), and activator protein 1 (AP-1) as being potentially important in study of thyroid disorders and as novel putative therapeutic drug targets. Notably, the thyroid receptor is a highly connected hub node and currently used as a therapeutic target in hypothyroidism. Our analysis represents the first comprehensive description of the thyroid pathway, which pertains to understanding the function of the protein and gene interaction networks. The findings from this study are therefore informative for pathophysiology and rational therapeutics of thyroid disorders.<\/jats:p>","DOI":"10.1089\/omi.2013.0007","type":"journal-article","created":{"date-parts":[[2013,9,17]],"date-time":"2013-09-17T11:21:49Z","timestamp":1379416909000},"page":"584-593","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["A Comprehensive Metabolic Modeling of Thyroid Pathway in Relation to Thyroid Pathophysiology and Therapeutics"],"prefix":"10.1177","volume":"17","author":[{"given":"Manish Kumar","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Bioinformatics, University Institute of Engineering and Technology, Chhatrapati Shahu Ji Maharaj University, Kanpur, 208024, Uttar Pradesh, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dev Bukhsh","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Institute of Biosciences and Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur, 208024, Uttar Pradesh, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohit","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, University Institute of Engineering and Technology, Chhatrapati Shahu Ji Maharaj University, Kanpur, 208024, Uttar Pradesh, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishna","family":"Misra","sequence":"additional","affiliation":[{"name":"Centre of Biomedical Magnetic Resonance","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2013,11]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10858"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.04.019"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm554"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1272"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1173299"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.10"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1740-2557-2-2"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1017"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2008.7"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4076(96)01818-0"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800911794519752"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2005.20.4.335"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1137\/070710111"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1666"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2007.04.002"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1478-5382(03)02370-9"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402482"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13721-013-0023-0"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.4172\/jcsb.1000090"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1228704"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1049\/sb:20045008"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039945"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.99"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037860"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2006.10.004"},{"key":"e_1_3_3_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039939"},{"key":"e_1_3_3_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2005.15.841"},{"key":"e_1_3_3_29_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a001651"},{"key":"e_1_3_3_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1558"},{"key":"e_1_3_3_31_1","first-page":"262","article-title":"Overexpression of phosphorylated-STAT3 and phosphorylated-ERK protein in dermatofibrosarcoma protuberans","volume":"16","author":"Lin N","year":"2006","unstructured":"Lin N, , Urabe K, , Moroi Y et al. 2006. 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