A method of risk prediction and pharmacodynamic prediction of furosemide based on EXOME analysis and panel design

摘要

#$%^&*AU2018102039A420190131.pdf#####ABSTRACT Furosemide is a loop diuretic widely used in the treatment of congestive heart failure and edema. While it can be used for first aid in the presence of heart failure, it has strong side effects, like hyperuricemia. So the aim of this method is to detect which genes or metabolic enzymes are susceptible to the use of furosemide in the first aid of heart failure and other situations and then give risk prediction and pharmacodynamic prediction of furosemic, so that furosemide can play the most effective role in the process of treating the patients. Our method constitutes of three part, namely the designing of the panel, genome comparison and getting the instruction report. In the first part, we searched the essays from PubMed about the gene's mutation about furosemide and then we screened out about 300 articles.The article contains 17 possible mutations, and we combined the discovery from PharmaGKB to integrate human-related genes, and we got 14 possible mutations about the efficacy of furosemide and concluded them into a database named 'dbknowledge'. In the second part, we made detailed analysis of the obtained genetic mutations based on the databases BWA, Picard-tools, GATK, and Annovar through the procedure including mapping, preprocessing, variants calling, variants filtration, annotation and selecting target region to acquire the multiple mutations on expressed region of human beings. Besides, we designed a perl program which could help compare the gene mutations we got to the database we established before. In the third part, we could get the instruction report which includes three parts 'the inspection result', 'detection of related annotation' and 'medical encyclopedia'. This report helps give the risk prediction of the furosemide, which is likely to be very useful in the clinical treatment.