METHOD TO IDENTIFY LIVER TOXICITY USING METABOLITE PROFILES
摘要
<p>The present disclosure relates to a methodology that identifies the underlying mechanisms that lead to hepatotoxicity. This is done by using the alterations in cellular metabolite profiles obtained before and after therapy/drug treatment in combination with a model of liver metabolism. Subsequently, by using a covariance matrix adaptation followed by evolutionary selection, it compares the drug-induced metabolite profiles obtained experimentally with those generated using the in silico model, automatically shortlists potential parameters whose alterations could have produced the drug-treated metabolite profile. Values of these parameters are estimated by formulating an optimal control problem to minimize the differences between the model-generated metabolite values and experimentally observed data. The estimated parameters are given as an input to the homeostatic liver model and simulations are carried out, thereby the results providing a mechanistic explanation for the development of toxicity.</p>
申请公布号
CA2824144(A1)
申请公布日期
2012.09.13
申请号
CA20122824144
申请日期
2012.03.05
申请人
STRAND LIFE SCIENCES PRIVATE LIMITED
发明人
SUBRAMANIAN, KALYANASUNDARAM;DAS, SONALI;KUMAR, RAJEEV;RAGHAVAN, SOWMYA;SHAIK, OSMAN SHAHI;CHAKRABARTI, PARTHA PRATIM;KRISHNAKUMAR, NARASIMHA MANDYAM;RAJESWARA, NALINI;BHAT, ANUPAMA RAJAN