title: Comprehensive Map of Molecules Implicated in Obesity.
abstract: Obesity is a global epidemic affecting over 1.5 billion people and is one of the risk factors for several diseases such as type 2 diabetes mellitus and hypertension. We have constructed a comprehensive map of the molecules reported to be implicated in obesity. A deep curation strategy was complemented by a novel semi-automated text mining system in order to screen 1,000 full-length research articles and over 90,000 abstracts that are relevant to obesity. We obtain a scale free network of 804 nodes and 971 edges, composed of 510 proteins, 115 genes, 62 complexes, 23 RNA molecules, 83 simple molecules, 3 phenotype and 3 drugs in "bow-tie" architecture. We classify this network into 5 modules and identify new links between the recently discovered fat mass and obesity associated FTO gene with well studied examples such as insulin and leptin. We further built an automated docking pipeline to dock orlistat as well as other drugs against the 24,000 proteins in the human structural proteome to explain the therapeutics and side effects at a network level. Based upon our experiments, we propose that therapeutic effect comes through the binding of one drug with several molecules in target network, and the binding propensity is both statistically significant and different in comparison with any other part of human structural proteome.
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, Noida [UP]-201 307, India.
authors.forename: Jaisri
authors.initials: J
authors.lastname: Jagannadham
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, Noida [UP]-201 307, India.
authors.forename: Hitesh Kumar
authors.initials: HK
authors.lastname: Jaiswal
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, Noida [UP]-201 307, India.
authors.forename: Stuti
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, Noida [UP]-201 307, India.
authors.forename: Kamal
authors.initials: K
authors.lastname: Rawal
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D050218:Body Fat Distribution; D057225:Data Mining; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007783:Lactones / Q000627:therapeutic use; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics*; D009765:Obesity / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077403:Orlistat; D011485:Protein Binding; D060066:Protein Interaction Maps / Q000235:genetics*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: D019440:Anti-Obesity Agents; D007328:Insulin; D007783:Lactones; D020738:Leptin; D011506:Proteins; D020543:Proteome; D000077403:Orlistat; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human