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@@ -32,3 +32,5 @@ saved_model/**/* filter=lfs diff=lfs merge=lfs -text
 *.zip filter=lfs diff=lfs merge=lfs -text
 *.zst filter=lfs diff=lfs merge=lfs -text
 *tfevents* filter=lfs diff=lfs merge=lfs -text
+data/PE-Designer/PE-Designer_NGG.csv filter=lfs diff=lfs merge=lfs -text
+data/PE-Designer/PE-Designer_offtargets_NGG.csv filter=lfs diff=lfs merge=lfs -text

app.py

@@ -18,7 +18,6 @@ from PIL import Image
 
 cwd=os.getcwd()+'/'+'data/'
 
-
 #get snps list
 snps = pd.read_csv("SNPS.csv")
 variants=snps['GENE:SNP'].unique()
@@ -98,12 +97,12 @@ def ForeCastBE(target_seq,method,select_method):
         ('ABE', 'CBE'),horizontal=True)
 
         if len(variant_spl)>1:
-            fname=variant_spl[1]+"_"+method+"_"+select_method+'.fasta'
+            fname=cwd+variant_spl[1]+"_"+method+"_"+select_method+'.fasta'
             res_fname=fname+"_"+Editor+'.csv'
 
             #snpid=variant_spl[1]
         else:
-            fname=variant_spl[0]+"_"+method+"_"+select_method+'.fasta'
+            fname=cwd+variant_spl[0]+"_"+method+"_"+select_method+'.fasta'
             res_fname=fname+"_"+Editor+'.csv'
             
             #snpid=variant_spl[0]
@@ -130,10 +129,10 @@ def ForeCastBE(target_seq,method,select_method):
             b +='import forecast_be\n'
             b+="forecast_be.predict_batch_fasta("+"'"+fname+"'"+",editor="+"'"+Editor+"'"+",output_path="+"'"+res_fname+"'"+",mean="+mean1+",std="+std1+")\n"
             
-            f = open(cwd+"pytest1.py", "w")
+            f = open("pytest1.py", "w")
             f.write(str(b))
             f.close()
-            command2 = 'python '+cwd+"pytest1.py"
+            command2 = 'python '+ "pytest1.py"
             #result = run(command2, stdout=PIPE, stderr=PIPE, universal_newlines=True, shell=True)
             run(command2, stdout=PIPE, stderr=PIPE, universal_newlines=True, shell=True)
             Forecast_BE_Res=pd.read_csv(res_fname)
@@ -524,6 +523,80 @@ def Guidescan2(method,select_method):
     
     display_res(method,',','query',select_method)
 
+def PE_DESIGNER(method,select_method):
+    st.header("PE-Designer: "+method)
+    expander = st.expander("Summary")
+    expander.markdown(
+    """
+    Prime Editors **(PEs)**, employes Cas9 nickase fused to an engineered reverse transcriptase template **(RTT, a wild-type Moloney Murine Leukemia Virus (M-MLV) for PE1 and mutagenised M-MLV in PE2 systems for enhanced DNA-RNA affinity, enzyme processivity, and thermostability)** via a gRNA called prime editing guide RNA **(pegRNA), can do all 12 edits.** PEs use pegRNA consisting of a 20 nt guide sequence, a primer binding site **(PBS)** and an RTT. The guide directs the Cas enzyme to a target site, the PBS hybridizes to the opposite strand to prime the reverse transcriptase, and the RTT integrates the desired genomic alteration.  
+    
+    **Optimized** PE2 (by employing additional sgRNA to nick the unedited strand so that cell's natural repair system copies the information in the edited strand to the complementary strand, permanently installing the edit) called PE3 and PE3b with reduced off-targets are commonly used.  
+    
+
+    """
+    )
+    #PE-Analyzer finds cleavage sites and defines 15-nt indi- cator sequences on both sides of the given input reference sequence within a user-defined comparison range (R) pa- rameter. PE-Analyzer selects the sequences, including both indicator sequences with up to a 1 bp mismatch, from the uploaded NGS data. PE-Analyzer counts the number of identical sequences and excludes the sequences with a lower count than a minimum frequency (the default value is 1) be- cause such sequences are considered to include sequencing errors. 
+    expander1 = st.expander("How it works")
+    expander1.markdown(
+        """
+        PEs use prime editing guide RNAs (pegRNAs) which is comprised of target sequence recognizing protospacer, RTT containing the desired edit, and a primer binding site for the activation of reverse transcriptase. While trafitional PE2 only requires a pegRNA, PE3 also requires a nicking guide RNA (ngRNA) for increased editing efficiency accompanying possible mutations derived from the presence of the ngRNA.  
+        PE-Designer provides all possible:
+        -   protospacer sequences
+        -   3′ extension sequences
+        -   ngRNA sequences
+        -   Potential off-target sites
+        """
+    )
+    expander2 = st.expander("References")
+    
+    expander2.write("[PE Designer Web App](http://www.rgenome.net/pe-designer/)")
+    expander2.write("[PE Designer Paper](https://academic.oup.com/nar/article/49/W1/W499/6262559)")
+    
+    expander3 = st.expander("Tool Options: All you can do with this tool")
+    
+    expander3.write(
+    """
+    This tool can be run for different PAM sequences including **NGG**, NRG etc. We only provide results for NGG.  
+    **As PEs can do all 12 edits, results on all possible 3-edits for a given single base edit are presented here**    
+    **Input:** We use 40 nt sequence with base of interest lying at position 20 for both reference input seq and desired edited sequence.
+    -   fasta files containing NT sequence (of the target and expected edited) are provided with the following format:
+        -   Target Sequence
+            -   Line1: >inp_seq 1
+            -   Line 2: Upto 1000 NT sequence
+        -   Desired edited Sequence
+            -   Line1: >inp_seq 1
+            -   Line 2: Upto 1000 NT sequence
+    **Output:** A csv file
+    -   Columns of interes
+        -   snp_ind
+        -   inp_seq
+        -   edited_seq
+        -   Target Sequence predicted by PE-Designer
+        -   Edit position
+        -   Type (pegRNA or nCas9)
+        -   Extension Sequence (for pegRNA)
+        -   Traget Sequence (for nCas9)
+    """
+    )
+    
+    #expander3.markdown(tips,unsafe_allow_html=True)
+    expander4 = st.expander("Scoring")
+    expander4.markdown(
+        """
+        This tool only reports potential off-targets alongwith number of mismatches.
+        """
+    )    
+    st.markdown("**Please note that the tool was run for all three edits for a given base.**")
+    st.markdown(caution,unsafe_allow_html=True)    
+    if method=='NGG':
+        target_seq = display_res(method,'\t','snp_id',select_method)
+        PE_Designer_Off=st.checkbox('Off-Targets')
+        if PE_Designer_Off:
+            display_res('offtargets_'+method,',','snp_id',select_method)
+    else:
+        st.markdown("**List coming soon**")
+
+    
 #Pnbdesigner
 def Pnbdesigner(method,select_method):
     st.header("PnB Designer: "+method)
@@ -1008,8 +1081,11 @@ def display_res(method,sep,rsid,select_method):
     if data_snp.shape[0] > 0:
         if select_method=='BE-DICT':
             return  data_snp['Outp_seq']
-        else:
+        elif select_method=='PnB Designer':
             return  data_snp['Protospacer']
+        else:
+            return [0]
+            
     else:
         return [0]
 
@@ -1025,19 +1101,22 @@ table_edit = '<p style="font-family:sans-serif; color:Green; font-size: 16px;">A
 
 
 st.title('Single Base Editiors')
+st.markdown('**Please select an option from the sidebar**')
 expander = st.expander("NEW TOOLS CURRENTLY AVAILABLE/COMING SOON IN THE APP")   
 #st.header('How to use this app')
 expander.markdown(
     """
-    **NEW: PLEASE NOTE THAT [FORECasT-BE](https://partslab.sanger.ac.uk/FORECasT-BE) is now part of the App to predict guide efficiency for ABEs and CBEs**
-    -   **Available under BE-DICT and PnB Designer options**
+    **NEW: PLEASE NOTE THAT**  
+    -   **[FORECasT-BE](https://partslab.sanger.ac.uk/FORECasT-BE) is now part of the App to predict guide efficiency for ABEs and CBEs**  
+        -   ***It can only be invoked from the local version of the app, Please download the app and run your local machine to use this feature.***
+        -   **Available under BE-DICT and PnB Designer options**
+    -   **Another Prime Editing tool [PE-Designer](http://www.rgenome.net/be-designer/) is also part of the app**
     **Coming Soon.**
     -   **We are also testing a prime editing efficiency calculator [MinsePIE](https://github.com/julianeweller/MinsePIE) and will be available soon**
-    -   **Another Prime and Base editing tool [PE/BE-Designer](http://www.rgenome.net/be-designer/) will also be part of the app soon**
     """
     )
 
-st.markdown('**Please select an option from the sidebar**')
+
 st.sidebar.image("logo-card-white.png", use_column_width=True)
 #ReadMe = st.sidebar.radio('ReadME',value=True)
 
@@ -1314,14 +1393,22 @@ else:
             "Please select an option",
             ('30bp_cpf1', '30bp_NGG','40bp_cpf1', '40bp_NGG','50bp_cpf1', '50bp_NGG'))
 
-    PnBDesigner = st.sidebar.checkbox('PnB Designer',key=5)
+    PE_DESIGNER1 = st.sidebar.checkbox('PE-Designer',key=5)
+    if PE_DESIGNER1:
+        select_method_PE_DESIGNER='PE-Designer'
+        method_PE_DESIGNER = st.sidebar.radio(
+            "Please select an option",
+            ('NGG','NRG'))
+
+
+    PnBDesigner = st.sidebar.checkbox('PnB Designer',key=6)
     if PnBDesigner:
         select_method_PnBDesigner='PnB Designer'
         method_PnBDesigner = st.sidebar.radio(
             "Please select an option",
             ('Base_editing_guides', 'Nicking_guides_PE3_PE3b','pegRNA_oligos'))
 
-    SNPCRISPR = st.sidebar.checkbox('SNP_CRISPR',key=6)
+    SNPCRISPR = st.sidebar.checkbox('SNP_CRISPR',key=7)
     if SNPCRISPR:
         select_method_SNPCRISPR='SNP_CRISPR'
         method_SNPCRISPR = st.sidebar.radio(
@@ -1339,6 +1426,9 @@ else:
     if GuideScan2 and select_method_GuideScan2 == "GuideScan2":
         Guidescan2(method_GuideScan2,select_method_GuideScan2)
 
+    if PE_DESIGNER1 and select_method_PE_DESIGNER == "PE-Designer":
+        PE_DESIGNER(method_PE_DESIGNER,select_method_PE_DESIGNER)
+
     if PnBDesigner and select_method_PnBDesigner=='PnB Designer':
         Pnbdesigner(method_PnBDesigner,select_method_PnBDesigner)
 

data/PE-Designer/PE-Designer_NGG.csv

@@ -0,0 +1,3 @@
+version https://git-lfs.github.com/spec/v1
+oid sha256:d613ed053a2ce392c8f9362e146ee8fb4581320945affbd013f112b106b07980
+size 12209007

data/PE-Designer/PE-Designer_offtargets_NGG.csv

@@ -0,0 +1,3 @@
+version https://git-lfs.github.com/spec/v1
+oid sha256:0d6d0380b5d042c580aacaf074698d9809388385e409f589218babab56575837
+size 153810851

data/pytest1.py

@@ -0,0 +1,2 @@
+import forecast_be
+forecast_be.predict_batch_fasta('rs510205_bystander_ABE8e_mean_BE-DICT.fasta',editor='ABE',output_path='rs510205_bystander_ABE8e_mean_BE-DICT.fasta_ABE.csv',mean=None,std=None)