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CodonShuffle.py
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executable file
·2048 lines (1816 loc) · 84.1 KB
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#!/usr/bin/python2.7
from __future__ import division
import os
import numpy
import scipy
import matplotlib
import pandas
import statsmodels
import patsy
import sys
import argparse
import matplotlib.pyplot as plt
import re
from random import shuffle,random,randint,choice,seed
from collections import Counter
from os import system
from pandas import DataFrame
from pandas import *
# import rpy2.robjects as robjects
# from rpy2.robjects.packages import importr
# from rpy2.robjects import pandas2ri
# pandas2ri.activate()
from Bio import SeqIO
from ggplot import *
from subprocess import call
from Bio.SeqRecord import SeqRecord
# utils = importr("utils")
# plyr = importr("plyr")
# seqinr = importr("seqinr")
#Constant values
#nt list
nts = ['A','C','G','T']
#Translation Table
tt = {"TTT":"F|Phe","TTC":"F|Phe","TTA":"L|Leu","TTG":"L|Leu","TCT":"S|Ser","TCC":"S|Ser","TCA":"S|Ser","TCG":"S|Ser", "TAT":"Y|Tyr","TAC":"Y|Tyr","TAA":"*|Stp","TAG":"*|Stp","TGT":"C|Cys","TGC":"C|Cys","TGA":"*|Stp","TGG":"W|Trp", "CTT":"L|Leu","CTC":"L|Leu","CTA":"L|Leu","CTG":"L|Leu","CCT":"P|Pro","CCC":"P|Pro","CCA":"P|Pro","CCG":"P|Pro","CAT":"H|His","CAC":"H|His","CAA":"Q|Gln","CAG":"Q|Gln","CGT":"R|Arg","CGC":"R|Arg","CGA":"R|Arg","CGG":"R|Arg", "ATT":"I|Ile","ATC":"I|Ile","ATA":"I|Ile","ATG":"M|Met","ACT":"T|Thr","ACC":"T|Thr","ACA":"T|Thr","ACG":"T|Thr", "AAT":"N|Asn","AAC":"N|Asn","AAA":"K|Lys","AAG":"K|Lys","AGT":"S|Ser","AGC":"S|Ser","AGA":"R|Arg","AGG":"R|Arg","GTT":"V|Val","GTC":"V|Val","GTA":"V|Val","GTG":"V|Val","GCT":"A|Ala","GCC":"A|Ala","GCA":"A|Ala","GCG":"A|Ala", "GAT":"D|Asp","GAC":"D|Asp","GAA":"E|Glu","GAG":"E|Glu","GGT":"G|Gly","GGC":"G|Gly","GGA":"G|Gly","GGG":"G|Gly"}
#Following functions or their combinations produce randomized or scrambled nucleotide sequence from input sequence.
#Amino-acid sequence of derived sequence is identical to the input sequence, but nucleotide composition (GC-, nucleotide, or dinucleotide content) may differ slightly for randomized sequences.
def gc3(seq):#this function creates sequence with GC-content close to the GC-content of the input sequence, but counts of nucleotides may differ from input sequence.
gc=at=0
for num in xrange(2,len(seq),3):#first calculating A+T and G+C of the input sequence in third codon position
if seq[num]=='A'or seq[num]=='T':
at+=1
elif seq[num]=='G'or seq[num]=='C':
gc+=1
at=at/(len(seq)/3.)
gc=gc/(len(seq)/3.)
seq1=[]
for num in xrange(2,len(seq),3):#list "seq1" will contain the first two nt of codon, third codon position will containe flags for subsequent randomization. Flags ('_Y_','_R_','_H_',or '_N_') correspond to IUPAC single-letter code, Y-Pyrimindine(C or T), R-Purine(A or G), H-Not G(A or C or T), N-any.
seq1+=seq[num-2:num],
if (seq[num]=='T'or seq[num]=='C')and(seq[num-2:num]=='TT'or seq[num-2:num]=='TA'or seq[num-2:num]=='TG'or seq[num-2:num]=='CA'or seq[num-2:num]=='AA'or seq[num-2:num]=='AG'or seq[num-2:num]=='GA'):
seq1+='_Y_',
elif (seq[num]=='A'or seq[num]=='G')and(seq[num-2:num]=='TT'or seq[num-2:num]=='CA'or seq[num-2:num]=='AA'or seq[num-2:num]=='AG'or seq[num-2:num]=='GA'):
seq1+='_R_',
elif seq[num-2:num+1]=='ATT'or seq[num-2:num+1]=='ATC'or seq[num-2:num+1]=='ATA':
seq1+='_H_',
elif (seq[num]=='A'or seq[num]=='G'or seq[num]=='T'or seq[num]=='C')and(seq[num-2:num]=='TC'or seq[num-2:num]=='CT'or seq[num-2:num]=='CC'or seq[num-2:num]=='CG'or seq[num-2:num]=='AC'or seq[num-2:num]=='GT'or seq[num-2:num]=='GC'or seq[num-2:num]=='GG'):
seq1+='_N_',
else: seq1+=seq[num],
seq2=''#"seq2" will contain the derived sequence, approproate nucleotide is chosen for flags in "seq1", according to GC-content
for i in seq1:
if i == '_Y_':
x=random()
if x<=gc:
seq2+='C'
elif gc<x<=gc+at:
seq2+='T'
else: seq2+=choice('TC')
elif i == '_R_':
x=random()
if x<=gc:
seq2+='G'
elif gc<x<=gc+at:
seq2+='A'
else: seq2+=choice('AG')
elif i == '_H_':
x=random()
if x<=gc:
seq2+='C'
elif gc<x<=gc+at:
seq2+=choice('AT')
else: seq2+=choice('ATC')
elif i == '_N_':
x=random()
if x<=gc:
seq2+=choice('GC')
elif gc<x<=gc+at:
seq2+=choice('AT')
else: seq2+=choice('AGTC')
else: seq2+=i
seq=seq2
return seq
def third_simple(seq):#this function creates scrambled sequence with the numbers of each nucleotide identical to the input sequence.
Y=[]
seq1=[]
for num in xrange(2,len(seq),3):
if (seq[num]=='T' or seq[num]=='C')and(seq[num-2:num]=='TT'or seq[num-2:num]=='TC'or seq[num-2:num]=='TA'or seq[num-2:num]=='TG'or seq[num-2:num]=='CT'or seq[num-2:num]=='CC'or seq[num-2:num]=='CA'or seq[num-2:num]=='CG'or seq[num-2:num]=='AT'or seq[num-2:num]=='AC'or seq[num-2:num]=='AA'or seq[num-2:num]=='AG'or seq[num-2:num]=='GU'or seq[num-2:num]=='GC'or seq[num-2:num]=='GA'or seq[num-2:num]=='GG'):
Y+=seq[num],
seq1+=seq[num-2:num],'_Y_',
else:seq1+=seq[num-2:num+1],
#now "seq1" contains flag '_Y_' in the third position of all codons, where C->T or T->C shuffling preserves the aminoacid sequence (i.e. PHE, SER etc.).
#C and T from the original sequence in this case would be extracted into list "Y"
shuffle(Y)#shuffling of list "Y". For example, before shuffling "Y" is ['C','T','C']; after - ['T','C','C']or['C','C','T']or['C','T','C']
seq2=''
for i in xrange(len(seq1)):
if seq1[i]=='_Y_':seq2+=Y.pop(0)#now elements of "Y" are inserted back into the sequence instead of '_Y_', but in a different order compared to the input sequence
else:seq2+=seq1[i]
seq=seq2
R=[]#similar to the previous step, but A and G are shuffled
seq1=[]
for num in xrange(2,len(seq),3):
if (seq[num]=='A' or seq[num]=='G')and(seq[num-2:num]=='TT'or seq[num-2:num]=='TC'or seq[num-2:num]=='CT'or seq[num-2:num]=='CC'or seq[num-2:num]=='CA'or seq[num-2:num]=='CG'or seq[num-2:num]=='AC'or seq[num-2:num]=='AA'or seq[num-2:num]=='AG'or seq[num-2:num]=='GT'or seq[num-2:num]=='GC'or seq[num-2:num]=='GA'or seq[num-2:num]=='GG'):
R+=seq[num],
seq1+=seq[num-2:num],'_R_',
else:seq1+=seq[num-2:num+1],
shuffle(R)
seq2=''
for i in xrange(len(seq1)):
if seq1[i]=='_R_':seq2+=R.pop(0)
else:seq2+=seq1[i]
seq=seq2
H=[]#similar to the previous step, but A,C, and T are shuffled. Affected aminoacids are ILE (three codons), four-codon and four-codon portion of six-codon aminoacids.
seq1=[]
for num in xrange(2,len(seq),3):
if (seq[num]=='A'or seq[num]=='C'or seq[num]=='T')and(seq[num-2:num]=='TC'or seq[num-2:num]=='CT'or seq[num-2:num]=='CC'or seq[num-2:num]=='CG'or seq[num-2:num]=='AT'or seq[num-2:num]=='AC'or seq[num-2:num]=='GT'or seq[num-2:num]=='GC'or seq[num-2:num]=='GG'):
H+=seq[num],
seq1+=seq[num-2:num],'_H_',
else:seq1+=seq[num-2:num+1],
shuffle(H)
seq2=''
for i in xrange(len(seq1)):
if seq1[i]=='_H_':seq2+=H.pop(0)
else:seq2+=seq1[i]
seq=seq2
N=[]#Shuffling of all four nucleotides, where possible. Affected aminoacids are four-codons and four-codon portion of six-codon aminoacids.
seq1=[]
for num in xrange(2,len(seq),3):
if (seq[num]=='A'or seq[num]=='C'or seq[num]=='T'or seq[num]=='G')and(seq[num-2:num]=='TC'or seq[num-2:num]=='CT'or seq[num-2:num]=='CC'or seq[num-2:num]=='CG'or seq[num-2:num]=='AC'or seq[num-2:num]=='GT'or seq[num-2:num]=='GC'or seq[num-2:num]=='GG'):
N+=seq[num],
seq1+=seq[num-2:num],'_N_',
else:seq1+=seq[num-2:num+1],
shuffle(N)
seq2=''
for i in xrange(len(seq1)):
if seq1[i]=='_N_':seq2+=N.pop(0)
else:seq2+=seq1[i]
seq=seq2
return seq
def dn23(seq):#this function creates a randomized sequence, with dinucleotide frequences in codon position 2-3 close to those of the input sequence.
aa=ag=ac=at=ga=gg=gc=gt=ca=cg=cc=ct=ta=tg=tc=tt=0
for num in xrange(2,len(seq),3):#first calculating dinucleotide frequences in codon position 2-3
if seq[num-1]=='A':
if seq[num]=='A':
aa+=1
elif seq[num]=='G':
ag+=1
elif seq[num]=='C':
ac+=1
elif seq[num]=='T':
at+=1
elif seq[num-1]=='G':
if seq[num]=='A':
ga+=1
elif seq[num]=='G':
gg+=1
elif seq[num]=='C':
gc+=1
elif seq[num]=='T':
gt+=1
elif seq[num-1]=='C':
if seq[num]=='A':
ca+=1
elif seq[num]=='G':
cg+=1
elif seq[num]=='C':
cc+=1
elif seq[num]=='T':
ct+=1
elif seq[num-1]=='T':
if seq[num]=='A':
ta+=1
elif seq[num]=='G':
tg+=1
elif seq[num]=='C':
tc+=1
elif seq[num]=='T':
tt+=1
aa,ag,ac,at,ga,gg,gc,gt,ca,cg,cc,ct,ta,tg,tc,tt=aa/(len(seq)/3.),ag/(len(seq)/3.),ac/(len(seq)/3.),at/(len(seq)/3.),ga/(len(seq)/3.),gg/(len(seq)/3.),gc/(len(seq)/3.),gt/(len(seq)/3.),ca/(len(seq)/3.),cg/(len(seq)/3.),cc/(len(seq)/3.),ct/(len(seq)/3.),ta/(len(seq)/3.),tg/(len(seq)/3.),tc/(len(seq)/3.),tt/(len(seq)/3.)
seq2=''
for num in xrange(2,len(seq),3):#now each codon is replaced with a synonimous codon according to the dinucleotide frequences in codon position 2-3
seq2+=seq[num-2:num]
if seq[num-1]=='A'and seq[num-2:num+1]!='TAA'and seq[num-2:num+1]!='TAG':
if seq[num]=='T'or seq[num]=='C':
space=at+ac
AT,AC=at/space,ac/space
x=random()
if x<=AT:
seq2+='T'
elif AT<x<=AT+AC:
seq2+='C'
elif seq[num]=='A'or seq[num]=='G':
space=aa+ag
AA,AG=aa/space,ag/space
x=random()
if x<=AA:
seq2+='A'
elif AA<x<=AA+AG:
seq2+='G'
else:seq2+=seq[num]
elif seq[num-1]=='G'and seq[num-2:num+1]!='TGA'and seq[num-2:num+1]!='TGG':
if (seq[num-2]=='T'or seq[num-2]=='A')and(seq[num]=='C'or seq[num]=='T'):
space = gt+gc
GT,GC=gt/space,gc/space
x=random()
if x<=GT:
seq2+='T'
elif GT<x<=GT+GC:
seq2+='C'
elif seq[num-2:num+1]=='AGA'or seq[num-2:num+1]=='AGG':
space=ga+gg
GA,GG=ga/space,gg/space
x=random()
if x<=GA:
seq2+='A'
elif GA<x<=GA+GG:
seq2+='G'
elif seq[num-2]=='C'or seq[num-2]=='G':
space=ga+gg+gc+gt
GA,GG,GC,GT=ga/space,gg/space,gc/space,gt/space
x=random()
if x<=GA:seq2+='A'
elif GA<x<=GA+GG:seq2+='G'
elif GA+GG<x<=GA+GG+GC:seq2+='C'
elif GA+GG+GC<x<=GA+GG+GC+GT:seq2+='T'
else:seq2+=seq[num]
elif seq[num-1]=='C':
space=ca+cg+cc+ct
CA,CG,CC,CT=ca/space,cg/space,cc/space,ct/space
x=random()
if x<=CA:seq2+='A'
elif CA<x<=CA+CG:seq2+='G'
elif CA+CG<x<=CA+CG+CC:seq2+='C'
elif CA+CG+CC<x<=CA+CG+CC+CT:seq2+='T'
elif seq[num-1]=='T':
if seq[num-2:num+1]=='TTT'or seq[num-2:num+1]=='TTC':
space = tt+tc
TT,TC=tt/space,tc/space
x=random()
if x<=TT:
seq2+='T'
elif TT<x<=TT+TC:
seq2+='C'
elif seq[num-2:num+1]=='TTA'or seq[num-2:num+1]=='TTG':
space = ta+tg
TA,TG=ta/space,tg/space
x=random()
if x<=TA:
seq2+='A'
elif TA<x<=TA+TG:
seq2+='G'
elif seq[num-2:num+1]=='ATT'or seq[num-2:num+1]=='ATC'or seq[num-2:num+1]=='ATA':
space=tt+tc+ta
TT,TC,TA=tt/space,tc/space,ta/space
x=random()
if x<=TA:seq2+='A'
elif TA<x<=TA+TC:seq2+='C'
elif TA+TC<x<=TA+TC+TT:seq2+='T'
elif seq[num-2]=='C'or seq[num-2]=='G':
space=ta+tg+tc+tt
TA,TG,TC,TT=ta/space,tg/space,tc/space,tt/space
x=random()
if x<=TA:seq2+='A'
elif TA<x<=TA+TG:seq2+='G'
elif TA+TG<x<=TA+TG+TC:seq2+='C'
elif TA+TG+TC<x<=TA+TG+TC+TT:seq2+='T'
else:seq2+=seq[num]
else:seq2+=seq[num]
seq=seq2
return seq
def third(seq):#this function creates sequence with dinucleotide content in codon positions 2-3 and 3-1 identical to that of the input sequence.
#logic of this function similar to "third_simple"
seq1=[]
TNT,TNC,TNA,TNG,GNT,GNA,GNC,GNG,CNG,CNA,CNT,CNC=[],[],[],[],[],[],[],[],[],[],[],[]#these lists will contain nucleotides from third codon position, with given [-1]and[+1]nucleotides to preserve dinucleotide content in conserved positions
#four-codon and four-codon portion of six-codon aminoacids are affected
for num in xrange(2,len(seq)-3,3):
seq1+=seq[num-2:num]
if seq[num]=='T' or seq[num]=='C' or seq[num]=='A' or seq[num]=='G':
if seq[num-2:num]=='CT' or seq[num-2:num]=='GT':#LEU4 or VAL
if seq[num+1]=='T':
seq1+='TNT',
TNT+=seq[num],
elif seq[num+1]=='C':
seq1+='TNC',
TNC+=seq[num],
elif seq[num+1]=='A':
seq1+='TNA',
TNA+=seq[num],
elif seq[num+1]=='G':
seq1+='TNG',
TNG+=seq[num],
else:
seq1+=seq[num]
elif seq[num-1]=='C':#SER4 or PRO or THR or ALA
if seq[num+1]=='T':
seq1+='CNT',
CNT+=seq[num],
elif seq[num+1]=='C':
seq1+='CNC',
CNC+=seq[num],
elif seq[num+1]=='A':
seq1+='CNA',
CNA+=seq[num],
elif seq[num+1]=='G':
seq1+='CNG',
CNG+=seq[num],
else:
seq1+=seq[num]
elif seq[num-2:num]=='CG' or seq[num-2:num]=='GG':#ARG4 or GLY
if seq[num+1]=='T':
seq1+='GNT',
GNT+=seq[num],
elif seq[num+1]=='C':
seq1+='GNC',
GNC+=seq[num],
elif seq[num+1]=='A':
seq1+='GNA',
GNA+=seq[num],
elif seq[num+1]=='G':
seq1+='GNG',
GNG+=seq[num],
else:
seq1+=seq[num]
else:
seq1+=seq[num]
else:
seq1+=seq[num]
seq1+=seq[-3:]
shuffle(TNT),shuffle(TNC),shuffle(TNA),shuffle(TNG),shuffle(GNG),shuffle(GNA),shuffle(GNT),shuffle(GNC),shuffle(CNT),shuffle(CNC),shuffle(CNA),shuffle(CNG)
seq2=''
for i in xrange(len(seq1)):
if seq1[i]=='TNT':seq2+=TNT.pop(0)
elif seq1[i]=='TNC':seq2+=TNC.pop(0)
elif seq1[i]=='TNG':seq2+=TNG.pop(0)
elif seq1[i]=='TNA':seq2+=TNA.pop(0)
elif seq1[i]=='GNT':seq2+=GNT.pop(0)
elif seq1[i]=='GNA':seq2+=GNA.pop(0)
elif seq1[i]=='GNC':seq2+=GNC.pop(0)
elif seq1[i]=='GNG':seq2+=GNG.pop(0)
elif seq1[i]=='CNT':seq2+=CNT.pop(0)
elif seq1[i]=='CNC':seq2+=CNC.pop(0)
elif seq1[i]=='CNG':seq2+=CNG.pop(0)
elif seq1[i]=='CNA':seq2+=CNA.pop(0)
else:seq2+=seq1[i]
seq=seq2
seq1=[]
THT,THC,THA,THG,GHT,GHA,GHC,GHG,CHG,CHA,CHT,CHC=[],[],[],[],[],[],[],[],[],[],[],[]
for num in xrange(2,len(seq)-3,3):
seq1+=seq[num-2:num]
if seq[num]=='T' or seq[num]=='C' or seq[num]=='A':
if seq[num-2:num]=='CT' or seq[num-2:num]=='GT' or seq[num-2:num]=='AT':#ILE3 or LEU4 or VAL
if seq[num+1]=='T':
seq1+='THT',
THT+=seq[num],
elif seq[num+1]=='C':
seq1+='THC',
THC+=seq[num],
elif seq[num+1]=='A':
seq1+='THA',
THA+=seq[num],
elif seq[num+1]=='G':
seq1+='THG',
THG+=seq[num],
else:
seq1+=seq[num]
elif seq[num-1]=='C':#SER4 or PRO or THR or ALA
if seq[num+1]=='T':
seq1+='CHT',
CHT+=seq[num],
elif seq[num+1]=='C':
seq1+='CHC',
CHC+=seq[num],
elif seq[num+1]=='A':
seq1+='CHA',
CHA+=seq[num],
elif seq[num+1]=='G':
seq1+='CHG',
CHG+=seq[num],
else:
seq1+=seq[num]
elif seq[num-2:num]=='CG' or seq[num-2:num]=='GG':#ARG4 or GLY
if seq[num+1]=='T':
seq1+='GHT',
GHT+=seq[num],
elif seq[num+1]=='C':
seq1+='GHC',
GHC+=seq[num],
elif seq[num+1]=='A':
seq1+='GHA',
GHA+=seq[num],
elif seq[num+1]=='G':
seq1+='GHG',
GHG+=seq[num],
else:
seq1+=seq[num]
else:
seq1+=seq[num]
else:
seq1+=seq[num]
seq1+=seq[-3:]
shuffle(THT),shuffle(THC),shuffle(THA),shuffle(THG),shuffle(GHG),shuffle(GHA),shuffle(GHT),shuffle(GHC),shuffle(CHT),shuffle(CHC),shuffle(CHA),shuffle(CHG)
seq2=''
for i in xrange(len(seq1)):
if seq1[i]=='THT':seq2+=THT.pop(0)
elif seq1[i]=='THC':seq2+=THC.pop(0)
elif seq1[i]=='THA':seq2+=THA.pop(0)
elif seq1[i]=='THG':seq2+=THG.pop(0)
elif seq1[i]=='GHT':seq2+=GHT.pop(0)
elif seq1[i]=='GHA':seq2+=GHA.pop(0)
elif seq1[i]=='GHC':seq2+=GHC.pop(0)
elif seq1[i]=='GHG':seq2+=GHG.pop(0)
elif seq1[i]=='CHT':seq2+=CHT.pop(0)
elif seq1[i]=='CHC':seq2+=CHC.pop(0)
elif seq1[i]=='CHG':seq2+=CHG.pop(0)
elif seq1[i]=='CHA':seq2+=CHA.pop(0)
else:seq2+=seq1[i]
seq=seq2
seq1=[]
TRT,TRC,TRA,TRG,ART,ARC,ARG,ARA,GRT,GRA,GRC,GRG,CRG,CRA,CRT,CRC=[],[],[],[],[],[],[],[],[],[],[],[],[],[],[],[]
for num in xrange(2,len(seq)-3,3):
seq1+=seq[num-2:num]
if seq[num]=='A' or seq[num]=='G':
if seq[num-1]=='T' and seq[num-2:num]!='AT':#not MET
if seq[num+1]=='T':
seq1+='TRT',
TRT+=seq[num],
elif seq[num+1]=='C':
seq1+='TRC',
TRC+=seq[num],
elif seq[num+1]=='A':
seq1+='TRA',
TRA+=seq[num],
elif seq[num+1]=='G':
seq1+='TRG',
TRG+=seq[num],
else:
seq1+=seq[num]
elif seq[num-1]=='C':
if seq[num+1]=='T':
seq1+='CRT',
CRT+=seq[num],
elif seq[num+1]=='C':
seq1+='CRC',
CRC+=seq[num],
elif seq[num+1]=='A':
seq1+='CRA',
CRA+=seq[num],
elif seq[num+1]=='G':
seq1+='CRG',
CRG+=seq[num],
else:
seq1+=seq[num]
elif seq[num-1]=='A' and seq[num-2:num]!='TA':#not Amber, not Ochre
if seq[num+1]=='T':
seq1+='ART',
ART+=seq[num],
elif seq[num+1]=='C':
seq1+='ARC',
ARC+=seq[num],
elif seq[num+1]=='A':
seq1+='ARA',
ARA+=seq[num],
elif seq[num+1]=='G':
seq1+='ARG',
ARG+=seq[num],
else:
seq1+=seq[num]
elif seq[num-1]=='G' and seq[num-2:num]!='TG':#not TRP, not Opal
if seq[num+1]=='T':
seq1+='GRT',
GRT+=seq[num],
elif seq[num+1]=='C':
seq1+='GRC',
GRC+=seq[num],
elif seq[num+1]=='A':
seq1+='GRA',
GRA+=seq[num],
elif seq[num+1]=='G':
seq1+='GRG',
GRG+=seq[num],
else:
seq1+=seq[num]
else:
seq1+=seq[num]
else:
seq1+=seq[num]
seq1+=seq[-3:]
shuffle(TRT),shuffle(TRC),shuffle(TRA),shuffle(TRG),shuffle(GRG),shuffle(GRA),shuffle(GRT),shuffle(GRC),shuffle(ARG),shuffle(ARC),shuffle(ART),shuffle(ARA),shuffle(CRT),shuffle(CRC),shuffle(CRA),shuffle(CRG)
seq2=''
for i in xrange(len(seq1)):
if seq1[i]=='TRT':seq2+=TRT.pop(0)
elif seq1[i]=='TRC':seq2+=TRC.pop(0)
elif seq1[i]=='TRA':seq2+=TRA.pop(0)
elif seq1[i]=='TRG':seq2+=TRG.pop(0)
elif seq1[i]=='ART':seq2+=ART.pop(0)
elif seq1[i]=='ARC':seq2+=ARC.pop(0)
elif seq1[i]=='ARG':seq2+=ARG.pop(0)
elif seq1[i]=='ARA':seq2+=ARA.pop(0)
elif seq1[i]=='GRT':seq2+=GRT.pop(0)
elif seq1[i]=='GRA':seq2+=GRA.pop(0)
elif seq1[i]=='GRC':seq2+=GRC.pop(0)
elif seq1[i]=='GRG':seq2+=GRG.pop(0)
elif seq1[i]=='CRT':seq2+=CRT.pop(0)
elif seq1[i]=='CRC':seq2+=CRC.pop(0)
elif seq1[i]=='CRG':seq2+=CRG.pop(0)
elif seq1[i]=='CRA':seq2+=CRA.pop(0)
else:seq2+=seq1[i]
seq=seq2
seq1=[]
TYT,TYC,TYA,TYG,AYT,AYC,AYG,AYA,GYT,GYA,GYC,GYG,CYG,CYA,CYT,CYC=[],[],[],[],[],[],[],[],[],[],[],[],[],[],[],[]
for num in xrange(2,len(seq)-3,3):
seq1+=seq[num-2:num]
if seq[num]=='T' or seq[num]=='C':
if seq[num-1]=='T':
if seq[num+1]=='T':
seq1+='TYT',
TYT+=seq[num],
elif seq[num+1]=='C':
seq1+='TYC',
TYC+=seq[num],
elif seq[num+1]=='A':
seq1+='TYA',
TYA+=seq[num],
elif seq[num+1]=='G':
seq1+='TYG',
TYG+=seq[num],
else:
seq1+=seq[num]
elif seq[num-1]=='C':
if seq[num+1]=='T':
seq1+='CYT',
CYT+=seq[num],
elif seq[num+1]=='C':
seq1+='CYC',
CYC+=seq[num],
elif seq[num+1]=='A':
seq1+='CYA',
CYA+=seq[num],
elif seq[num+1]=='G':
seq1+='CYG',
CYG+=seq[num],
else:
seq1+=seq[num]
elif seq[num-1]=='A':
if seq[num+1]=='T':
seq1+='AYT',
AYT+=seq[num],
elif seq[num+1]=='C':
seq1+='AYC',
AYC+=seq[num],
elif seq[num+1]=='A':
seq1+='AYA',
AYA+=seq[num],
elif seq[num+1]=='G':
seq1+='AYG',
AYG+=seq[num],
else:
seq1+=seq[num]
elif seq[num-1]=='G':
if seq[num+1]=='T':
seq1+='GYT',
GYT+=seq[num],
elif seq[num+1]=='C':
seq1+='GYC',
GYC+=seq[num],
elif seq[num+1]=='A':
seq1+='GYA',
GYA+=seq[num],
elif seq[num+1]=='G':
seq1+='GYG',
GYG+=seq[num],
else:
seq1+=seq[num]
else:
seq1+=seq[num]
else:
seq1+=seq[num]
seq1+=seq[-3:]
shuffle(TYT),shuffle(TYC),shuffle(TYA),shuffle(TYG),shuffle(GYG),shuffle(GYA),shuffle(GYT),shuffle(GYC),shuffle(AYG),shuffle(AYC),shuffle(AYT),shuffle(AYA),shuffle(CYT),shuffle(CYC),shuffle(CYA),shuffle(CYG)
seq2=''
for i in xrange(len(seq1)):
if seq1[i]=='TYT':seq2+=TYT.pop(0)
elif seq1[i]=='TYC':seq2+=TYC.pop(0)
elif seq1[i]=='TYA':seq2+=TYA.pop(0)
elif seq1[i]=='TYG':seq2+=TYG.pop(0)
elif seq1[i]=='AYT':seq2+=AYT.pop(0)
elif seq1[i]=='AYC':seq2+=AYC.pop(0)
elif seq1[i]=='AYG':seq2+=AYG.pop(0)
elif seq1[i]=='AYA':seq2+=AYA.pop(0)
elif seq1[i]=='GYT':seq2+=GYT.pop(0)
elif seq1[i]=='GYA':seq2+=GYA.pop(0)
elif seq1[i]=='GYC':seq2+=GYC.pop(0)
elif seq1[i]=='GYG':seq2+=GYG.pop(0)
elif seq1[i]=='CYT':seq2+=CYT.pop(0)
elif seq1[i]=='CYC':seq2+=CYC.pop(0)
elif seq1[i]=='CYG':seq2+=CYG.pop(0)
elif seq1[i]=='CYA':seq2+=CYA.pop(0)
else:seq2+=seq1[i]
return seq2
def exchange6deg(seq):#this function shuffles the first nucleotide for two six-codon aminoacids (LEU and ARG) with the third codon position,
#preserving overall dinucleotide content, but not position-specific dinucleotide content. For SER (TCN+AGY)shuffling is more complicated, see below.
#after this shuffling, the 'third'-function should be used as above
#LEU
seq1=[]
#LEU has TTR and CTN codons
#first convertion of CTY to CTR is required to make them compatible with TTR codons and improve the shuffling efficiency;
#CTY LEU codons might be re-introduced later upon the third-position shuffling
CTYT=[]#these lists will contain third nucleotides of CTY-codons
CTYA=[]
CTTG=[]
CTCG=[]#T/C separation for shuffling of ARG, (A->C)
CTYC=[]
TAT,TAA,TAG,TAC,TGT,TGA,TGG,TGC=[],[],[],[],[],[],[],[]#these lists will contain the third R-nucleotide of ILE and VAL to exchange with the first position of Leu
TAG_arg=[]#only 'A' to 'C'. Arginine has AGY and CGN codons, first position can be shuffled.
seq1+=seq[:2]
for num in xrange(2,len(seq)-2,1):
#seq1+=seq[num-2:num]
if num%3==2 and seq[num-2:num]=='CT' and (seq[num]=='C' or seq[num]=='T'):
if seq[num+1]=='A':
CTYA+=seq[num],
seq1+='CTYA',
elif seq[num+1]=='G':
if seq[num]=='C':#T/C separation because of ARG, (A->C)
CTCG+=seq[num],
seq1+='CTYG',
elif seq[num]=='T':
CTTG+=seq[num],
seq1+='CTYG',
elif seq[num+1]=='C':
CTYC+=seq[num],
seq1+='CTYC',
elif seq[num+1]=='T':
CTYT+=seq[num],
seq1+='CTYT',
else:
seq1+=seq[num],
elif num%3==2 and (seq[num-2:num+1]=='GTA'or seq[num-2:num+1]=='ATA'):
if seq[num+1]=='A':
TAA+=seq[num],
seq1+='TAA',
elif seq[num+1]=='G':
TAG+=seq[num],
seq1+='TAG',
elif seq[num+1]=='C':
TAC+=seq[num],
seq1+='TAC',
elif seq[num+1]=='T':
TAT+=seq[num],
seq1+='TAT',
else:
seq1+=seq[num],
elif num%3==2 and seq[num-2:num+1]=='GTG':
if seq[num+1]=='A':
TGA+=seq[num],
seq1+='TGA',
elif seq[num+1]=='G':
TGG+=seq[num],
seq1+='TGG',
elif seq[num+1]=='C':
TGC+=seq[num],
seq1+='TGC',
elif seq[num+1]=='T':
TGT+=seq[num],
seq1+='TGT',
else:
seq1+=seq[num],
elif num%3==0 and (seq[num:num+3]=='AGA' or seq[num:num+3]=='AGG') and seq[num-1]=='T'and seq[num-2:num]!='TT'and seq[num-3:num]!='CTT':
TAG_arg+=seq[num],
seq1+='TAG_arg',
else:
seq1+=seq[num],
seq1+=seq[-2:]
#now replacing the third position Y with R in LEU
CTAG=[]
change_num=min(len(CTCG),len(TAG_arg))
CTAG,TAG_arg[:change_num],CTCG=TAG_arg[:change_num],CTCG[:change_num],CTCG[-1*(len(CTCG)-change_num):]
CTYG=CTCG+CTTG
shuffle(CTYG)
change_num=min(len(CTYG),len(TAG)) #first TAN,
CTYG[:change_num],TAG[:change_num]=TAG[:change_num],CTYG[:change_num] #then TGN,
CTYG.reverse() #important,
change_num=min(len(CTYG),len(TGG)) #Arginine,
CTYG[:change_num],TGG[:change_num]=TGG[:change_num],CTYG[:change_num] #first TAN,
CTYG+=CTAG #then TGN,
#important,
change_num=min(len(CTYT),len(TAT)) #first TAN,
CTYT[:change_num],TAT[:change_num]=TAT[:change_num],CTYT[:change_num] #then TGN,
CTYT.reverse() #important,
change_num=min(len(CTYT),len(TGT)) #first TAN,
CTYT[:change_num],TGT[:change_num]=TGT[:change_num],CTYT[:change_num] #then TGN,
#important,
#first TAN,
change_num=min(len(CTYA),len(TAA)) #then TGN,
CTYA[:change_num],TAA[:change_num]=TAA[:change_num],CTYA[:change_num] #important,
CTYA.reverse() #Arginine,
change_num=min(len(CTYA),len(TGA)) #then TGN,
CTYA[:change_num],TGA[:change_num]=TGA[:change_num],CTYA[:change_num] #important,
#first TAN,
#then TGN,
change_num=min(len(CTYC),len(TAC)) #important,
CTYC[:change_num],TAC[:change_num]=TAC[:change_num],CTYC[:change_num] #first TAN,
CTYC.reverse() #important,
change_num=min(len(CTYC),len(TGC)) #Arginine,
CTYC[:change_num],TGC[:change_num]=TGC[:change_num],CTYC[:change_num] #important
shuffle(CTYT),shuffle(CTYA),shuffle(CTYG),shuffle(CTYC),shuffle(TAT),shuffle(TAA),shuffle(TAG),shuffle(TAC),shuffle(TGT),shuffle(TGA),shuffle(TGG),shuffle(TGC),shuffle(TAG_arg)
seq2=''
for i in xrange(len(seq1)):
if seq1[i]=='CTYT':seq2+=CTYT.pop(0)
elif seq1[i]=='CTYC':seq2+=CTYC.pop(0)
elif seq1[i]=='CTYA':seq2+=CTYA.pop(0)
elif seq1[i]=='CTYG':seq2+=CTYG.pop(0)
elif seq1[i]=='TAG':seq2+=TAG.pop(0)
elif seq1[i]=='TAA':seq2+=TAA.pop(0)
elif seq1[i]=='TAC':seq2+=TAC.pop(0)
elif seq1[i]=='TAT':seq2+=TAT.pop(0)
elif seq1[i]=='TGG':seq2+=TGG.pop(0)
elif seq1[i]=='TGA':seq2+=TGA.pop(0)
elif seq1[i]=='TGC':seq2+=TGC.pop(0)
elif seq1[i]=='TGT':seq2+=TGT.pop(0)
elif seq1[i]=='TAG_arg':seq2+=TAG_arg.pop(0)
else:seq2+=seq1[i]
seq=seq2#convertion of CTY to CTR is finished
#now shuffling the first nucleotide of TTR and CTR LEU codons, and the third Y of other codons
seq1=[]
TYT,AYT,GYT,CYT=[],[],[],[]
seq1+=seq[:2]
for num in xrange(2,len(seq)-2,1):
if ((seq[num]=='T' or seq[num]=='C') and seq[num+1]=='T' and num%3==2 and seq[num+1:num+4]!='TTA' and seq[num+1:num+4]!='TTG' and seq[num+1:num+4]!='CTA' and seq[num+1:num+4]!='CTG') or (num%3==0 and (seq[num:num+3]=='TTA' or seq[num:num+3]=='TTG' or seq[num:num+3]=='CTA' or seq[num:num+3]=='CTG')):
if seq[num-1]=='T':
seq1+='TYT',
TYT+=seq[num],
elif seq[num-1]=='C':
seq1+='CYT',
CYT+=seq[num],
elif seq[num-1]=='A':
seq1+='AYT',
AYT+=seq[num],
elif seq[num-1]=='G':
seq1+='GYT',
GYT+=seq[num],
else:
seq1+=seq[num]
else:
seq1+=seq[num]
seq1+=seq[-2:]
shuffle(TYT),shuffle(GYT),shuffle(AYT),shuffle(CYT)
seq2=''
for i in xrange(len(seq1)):
if seq1[i]=='TYT':seq2+=TYT.pop(0)
elif seq1[i]=='AYT':seq2+=AYT.pop(0)
elif seq1[i]=='GYT':seq2+=GYT.pop(0)
elif seq1[i]=='CYT':seq2+=CYT.pop(0)
else:seq2+=seq1[i]
seq=seq2#shuffling is finished
#SER
seq1=[]
TCRC,TCRA,TCRG,TCRT=[],[],[],[]#SER has TCN and AGY codons, first TCR will be converted to TCY
CYC,CYA,CYG,CYT=[],[],[],[]
for num in xrange(2,len(seq)-2,3):
seq1+=seq[num-2:num]
if seq[num-2:num+1]=='TCA' or seq[num-2:num+1]=='TCG':
if seq[num+1]=='C':
TCRC+=seq[num],
seq1+='TCRC',
elif seq[num+1]=='G':
TCRG+=seq[num],
seq1+='TCRG',
elif seq[num+1]=='A':
TCRA+=seq[num],
seq1+='TCRA',
elif seq[num+1]=='T':
TCRT+=seq[num],
seq1+='TCRT',
else:
seq1+=seq[num],
elif (seq[num-2:num]=='CC'or seq[num-2:num]=='AC' or seq[num-2:num]=='GC')and(seq[num]=='T'or seq[num]=='C'):
if seq[num+1]=='C':
CYC+=seq[num],
seq1+='CYC',
elif seq[num+1]=='G':
CYG+=seq[num],
seq1+='CYG',
elif seq[num+1]=='A':
CYA+=seq[num],
seq1+='CYA',
elif seq[num+1]=='T':
CYT+=seq[num],
seq1+='CYT',
else:
seq1+=seq[num],
else:
seq1+=seq[num],
seq1+=seq[-3:]
change_num=min(len(TCRC),len(CYC))
TCRC[:change_num],CYC[:change_num]=CYC[:change_num],TCRC[:change_num]
change_num=min(len(TCRA),len(CYA))
TCRA[:change_num],CYA[:change_num]=CYA[:change_num],TCRA[:change_num]
change_num=min(len(TCRG),len(CYG))
TCRG[:change_num],CYG[:change_num]=CYG[:change_num],TCRG[:change_num]
change_num=min(len(TCRT),len(CYT))
TCRT[:change_num],CYT[:change_num]=CYT[:change_num],TCRT[:change_num]
shuffle(TCRC),shuffle(TCRA),shuffle(TCRG),shuffle(TCRT),shuffle(CYC),shuffle(CYA),shuffle(CYG),shuffle(CYT)
seq2=''
for i in xrange(len(seq1)):
if seq1[i]=='TCRC':seq2+=TCRC.pop(0)
elif seq1[i]=='TCRA':seq2+=TCRA.pop(0)
elif seq1[i]=='TCRG':seq2+=TCRG.pop(0)
elif seq1[i]=='TCRT':seq2+=TCRT.pop(0)
elif seq1[i]=='CYT':seq2+=CYT.pop(0)
elif seq1[i]=='CYA':seq2+=CYA.pop(0)
elif seq1[i]=='CYG':seq2+=CYG.pop(0)
elif seq1[i]=='CYC':seq2+=CYC.pop(0)
else:seq2+=seq1[i]
seq=seq2#convertion is finished
#ATCY,AAGY conversion to BTCY,BAGY
seq1=[]
AAA_R,GAA_N,GAA_R,CAA_N,TAA_R,TAA_N,TAA_H,AAT_R,GAT_N,GAT_R,CAT_N,TAT_R,TAT_N,TAT_H=[],[],[],[],[],[],[],[],[],[],[],[],[],[]
AGA_R,GBA_N,GGA_R,TGA_R,TBA_N,TYA_H,AGT_R,GBT_N,GGT_R,CBT_N,TGT_R,TBT_N,TYT_H,CBA_N=[],[],[],[],[],[],[],[],[],[],[],[],[],[]
for num in xrange(2,len(seq)-2,3):
seq1+=seq[num-2:num]
if seq[num:num+4]=='AAGC'or seq[num:num+4]=='AAGT':
if seq[num-2:num]=='CA'or seq[num-2:num]=='AA'or seq[num-2:num]=='GA':
AAA_R+=seq[num],
seq1+='AAA_R',
elif seq[num-2:num]=='CG'or seq[num-2:num]=='GG':
GAA_N+=seq[num],
seq1+='GAA_N',
elif seq[num-2:num]=='AG':
GAA_R+=seq[num],
seq1+='GAA_R',
elif seq[num-2:num]=='CC'or seq[num-2:num]=='AC'or seq[num-2:num]=='GC':
CAA_N+=seq[num],
seq1+='CAA_N',
elif seq[num-2:num]=='TT':
TAA_R+=seq[num],
seq1+='TAA_R',
elif seq[num-2:num]=='CT'or seq[num-2:num]=='GT':
TAA_N+=seq[num],
seq1+='TAA_N',
elif seq[num-2:num]=='AT':
TAA_H+=seq[num],
seq1+='TAA_H',
else:
seq1+=seq[num]
elif seq[num:num+4]=='ATCC'or seq[num:num+4]=='ATCT':
if seq[num-2:num]=='CA'or seq[num-2:num]=='AA'or seq[num-2:num]=='GA':
AAT_R+=seq[num],
seq1+='AAT_R',
elif seq[num-2:num]=='CG'or seq[num-2:num]=='GG':
GAT_N+=seq[num],
seq1+='GAT_N',
elif seq[num-2:num]=='AG':
GAT_R+=seq[num],
seq1+='GAT_R',
elif seq[num-2:num]=='CC'or seq[num-2:num]=='AC'or seq[num-2:num]=='GC':
CAT_N+=seq[num],
seq1+='CAT_N',
elif seq[num-2:num]=='TT':
TAT_R+=seq[num],
seq1+='TAT_R',
elif seq[num-2:num]=='CT'or seq[num-2:num]=='GT':
TAT_N+=seq[num],
seq1+='TAT_N',
elif seq[num-2:num]=='AT':
TAT_H+=seq[num],
seq1+='TAT_H',
else:
seq1+=seq[num]
elif seq[num+1:num+4]!='AGC'and seq[num+1:num+4]!='AGT'and seq[num+1]=='A'and seq[num]!='A':
if seq[num-2:num+1]=='CAG'or seq[num-2:num+1]=='AAG'or seq[num-2:num+1]=='GAG':
AGA_R+=seq[num],
seq1+='AGA_R',
elif seq[num-2:num]=='CG'or seq[num-2:num]=='GG':
GBA_N+=seq[num],
seq1+='GBA_N',
elif seq[num-2:num+1]=='AGG':
GGA_R+=seq[num],
seq1+='GGA_R',
elif seq[num-2:num]=='CC'or seq[num-2:num]=='AC'or seq[num-2:num]=='GC':
CBA_N+=seq[num],
seq1+='CBA_N',
elif seq[num-2:num+1]=='TTG':
TGA_R+=seq[num],
seq1+='TGA_R',
elif seq[num-2:num]=='CT'or seq[num-2:num]=='GT':
TBA_N+=seq[num],
seq1+='TBA_N',
elif seq[num-2:num]=='AT'and seq[num]!='G':
TYA_H+=seq[num],
seq1+='TYA_H',
else:
seq1+=seq[num]
elif seq[num+1:num+4]!='TCC'and seq[num+1:num+4]!='TCT'and seq[num+1]=='T'and seq[num]!='A':
if seq[num-2:num+1]=='CAG'or seq[num-2:num+1]=='AAG'or seq[num-2:num+1]=='GAG':
AGT_R+=seq[num],
seq1+='AGT_R',
elif seq[num-2:num]=='CG'or seq[num-2:num]=='GG':
GBT_N+=seq[num],
seq1+='GBT_N',
elif seq[num-2:num+1]=='AGG':
GGT_R+=seq[num],
seq1+='GGT_R',
elif seq[num-2:num]=='CC'or seq[num-2:num]=='AC'or seq[num-2:num]=='GC':
CBT_N+=seq[num],
seq1+='CBT_N',
elif seq[num-2:num+1]=='TTG':
TGT_R+=seq[num],
seq1+='TGT_R',
elif seq[num-2:num]=='CT'or seq[num-2:num]=='GT':
TBT_N+=seq[num],
seq1+='TBT_N',
elif seq[num-2:num]=='AT'and seq[num]!='G':
TYT_H+=seq[num],
seq1+='TYT_H',
else:
seq1+=seq[num]
else:
seq1+=seq[num]
seq1+=seq[-3:]
change_num=min(len(AAA_R),len(AGA_R))
AAA_R[:change_num],AGA_R[:change_num]=AGA_R[:change_num],AAA_R[:change_num]
change_num=min(len(GAA_R),len(GGA_R))
GAA_R[:change_num],GGA_R[:change_num]=GGA_R[:change_num],GAA_R[:change_num]
change_num=min(len(TAA_R),len(TGA_R))
TAA_R[:change_num],TGA_R[:change_num]=TGA_R[:change_num],TAA_R[:change_num]
change_num=min(len(AAT_R),len(AGT_R))
AAT_R[:change_num],AGT_R[:change_num]=AGT_R[:change_num],AAT_R[:change_num]
change_num=min(len(GAT_R),len(GGT_R))
GAT_R[:change_num],GGT_R[:change_num]=GGT_R[:change_num],GAT_R[:change_num]
change_num=min(len(TAT_R),len(TGT_R))
TAT_R[:change_num],TGT_R[:change_num]=TGT_R[:change_num],TAT_R[:change_num]
change_num=min(len(TAT_H),len(TYT_H))
TAT_H[:change_num],TYT_H[:change_num]=TYT_H[:change_num],TAT_H[:change_num]
change_num=min(len(TAA_H),len(TYA_H))
TAA_H[:change_num],TYA_H[:change_num]=TYA_H[:change_num],TAA_H[:change_num]
change_num=min(len(CAA_N),len(CBA_N))