Accession Number : AD1018490

Title :   Novel High-Fidelity Screening of Environmental Chemicals and Carcinogens and Mechanisms in Colorectal Cancer.

Descriptive Note : Technical Report,01 Sep 2015,31 Aug 2016

Corporate Author : Georgetown University Washington United States

Personal Author(s) : Dakshanamurthy,Sivanesan ; Wathieu,Henri ; Byers,Stephen ; Ojo,Abiola

Full Text :

Report Date : 01 Sep 2016

Pagination or Media Count : 119

Abstract : Environmental chemicals (ECs) include chemical warfare agents and carcinogens confer potential cancer risks to Military personnel and their families during service. The relative contribution of EC exposure and genetic susceptibility in the etiology of cancer is poorly understood making the translation of existing data into meaningful prevention and/or therapeutic strategies for Military personnel difficult. To that end, we develop a platform for the predictive biological assessment of ECs through two foci: (1) predicting empirical EC-protein target associations by a proteochemometric method called Tox-TMFS and incorporating systems biology analysis to model the cancer-linked cellular activity of the EC using Net-TMFS, now called as DrugGenEx-Net, and (2) a novel method entitled the chemo-phenotypic based toxicity measurement (CPTM)that integrates EC-target biological effects with ADME toxicokinetic parameters and intrinsic chemical reactivity properties into a quantifiable toxicity score (Zts). We hypothesize that our novel in-silico screening method will identify mechanisms through finding targets/pathways with unprecedented accuracy and identify which ECs have the potential to influence the development of cancer. As biological effects are driven by EC interactions with biological entities such as proteins, we completed a computational systems biology model called Tox-TMFS that predicts EC-protein target signatures and relates them to higher-order effects that include protein-protein interactions, signaling pathways, and molecular functions using DrugGenEx-Net. We have carried out and validated Tox-TMFS and DrugGenEx-Net procedures by querying predicted EC-target and EC-molecular function signatures against external databases. [truncated]

Descriptors :   carcinoma , colon cancer , cancer research , Toxicity , Pharmacokinetics , metabolism

Distribution Statement : APPROVED FOR PUBLIC RELEASE