Lab specific validation calibration 2020

BNet/Bnet.R

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+#Bnet calculation Github
+hERG_par="/data/results_1s_HT_Bmax"
+otherCh_path="/data/non_hERG/results"
+cmaxfile<-"data/newCiPA1.csv"
+DRUGNAMES=c("dofetilide","bepridil","sotalol","quinidine","cisapride","terfenadine","ondansetron","chlorpromazine","verapamil","ranolazine","mexiletine","diltiazem","disopyramide","ibutilide","vandetanib","azimilide","droperidol","domperidone","clarithromycin","risperidone","pimozide","clozapine","metoprolol","loratadine","tamoxifen","nifedipine","nitrendipine","astemizole")
+Bnet2=vector()
+for (drug in DRUGNAMES) {
+params=block1=Ochparams=ICaLparams=INaLparams=INaparams=vector()
+drugtable<-read.csv(cmaxfile)
+all_herg_par<-read.csv(sprintf("%s/%s/IC50_samples.csv",hERG_par,drug))
+otherCh=read.csv(sprintf("%s/%s/IC50_samples.csv",otherCh_path,drug))
+print(sprintf("%s/%s/IC50_samples.csv",otherCh_path,drug))
+cmax<-drugtable[tolower(as.character(drugtable$drug))==drug,"therapeutic"] # should be in nanomolar
+doses=c(1,2,3,4)
+for (i in 1:2000) {
+	params[1]=all_herg_par[i,"hERG_IC50"]
+	params[2]=all_herg_par[i,"hERG_h"]
+
+	ICaLparams[1]=otherCh[i,"ICaL_IC50"]
+	ICaLparams[2]=otherCh[i,"ICaL_h"]
+
+	INaparams[1]=otherCh[i,"INa_IC50"]
+	INaparams[2]=otherCh[i,"INa_h"]
+
+	INaLparams[1]=otherCh[i,"INaL_IC50"]
+	INaLparams[2]=otherCh[i,"INaL_h"]
+
+        for(dose in doses){
+            conc<-dose*cmax
+			block=100*(1-1/(1+(conc/params[1])^params[2]))
+			blockICaL=100*(1-1/(1+(conc/ICaLparams[1])^ICaLparams[2]))
+			blockINa=100*(1-1/(1+(conc/INaparams[1])^INaparams[2]))
+			blockINaL=100*(1-1/(1+(conc/INaLparams[1])^INaLparams[2]))
+			Bnet=block-(blockICaL+blockINaL)
+			block0=c(block,blockICaL,blockINa,blockINaL,Bnet,conc,dose,i,params,ICaLparams,INaparams,INaLparams)
+
+block1=rbind(block1,block0)
+		}
+   }
+   colnames(block1)=c("blockhERG","blockICaL","blockINa","blockINaL","Bnet","conc","dose","i","IhERG","hhERGparams","ICaLparams","hICaLparams","INaparams","hINaparams","INaLparams","hINaLparams")
+   write.csv(block1,paste0("results/",drug,"_block2.csv"))
+   Bnet1=c(drug,mean(block1[,5]),quantile(block1[,5], probs = c(0.025, 0.975), na.rm = FALSE, names = TRUE))
+   Bnet2=rbind(Bnet2,Bnet1)
+}
+write.csv(Bnet2,paste0("results/","Bnet2.csv"))

BNet/data/non_hERG/results/astemizole/IC50_optimal.csv

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+ICaL_IC50,ICaL_h,INa_IC50,INa_h,INaL_IC50,INaL_h,hERG_IC50,hERG_h
+972,1.98,1862,1.98,786.5,1.98,27.01,1.504