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ddgun_seq.py
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#!/usr/bin/python
## Copyright (C) 2019 Ludovica Montanucci, Emidio Capriotti and Piero Fariselli
##
## This program and all program in this package are free software;
## you can redistribute it and/or modify it under the terms of the
## GNU General Public License as published by the Free Software
## Foundation; either version 2 of the License, or (at your option)
## any later version.
##
## This program is distributed in the hope that it will be useful,
## but WITHOUT ANY WARRANTY; without even the implied warranty of
## MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
## GNU General Public License for more details.
##
## You should have received a copy of the GNU General Public License
## along with this program; if not, write to the Free Software
## Foundation, Inc., 59 Temple Place - Suite 330, Boston, MA 02111-1307, USA
##
## REFERENCES
##
## Montanucci L, Capriotti E, Frank Y, Ben-Tal N, Fariselli P. (2019).
## DDGun: an untrained method for the prediction of protein stability
## changes upon single and multiple point variations.
## BMC Bioinformatics. 20 (Suppl 14): 335. PMID:31266447
##
import csv
import _pickle as cPickle
import os, sys, pickle, tempfile, argparse
from subprocess import getstatusoutput
import numpy as np
global pblast, uniclust30, pprof, prog_path, data_path, aalist
prog_path=os.path.dirname(os.path.abspath(__file__))
data_path=prog_path+'/data_ddgun'
tool_path=prog_path+'/tools'
util_path=prog_path+'/utils'
data_path=prog_path+'/data_ddgun'
sys.path.append(tool_path)
from hsspTools import readHSSP, hssp2dic
aalist='ARNDCQEGHILKMFPSTWYV'
pprof=tool_path+'/ali2prof.py'
pblast = 'hhblits'
#pblast=util_path+'/hh-suite/build/bin/hhblits' #/hh-suite/bin/hhblits ##DDGun origional
#uniclust30=data_path+'/uniclust30_2018_08/uniclust30_2018_08' #/uniclust30_2018_08/uniclust30_2018_08
#uniclust30=hhblits_db
def read_csv(file_name):
mut_list = []
with open(file_name, 'r') as file:
reader = csv.reader(file)
for row in reader:
mut_list.append(row)
return mut_list
def get_options():
global uniclust30, pblast
parser = argparse.ArgumentParser(description='Program for generating protein mutations features.')
#parser.add_argument ('seqfile', type=str)
#parser.add_argument ('mutations')
parser.add_argument ("--aa1", "--aaindex1", action="store",type=str, dest="aa1", help="Potential aaindex1")
parser.add_argument ("--aa2", "--aaindex2", action="store",type=str, dest="aa2", help="Potential aaindex2")
parser.add_argument ("--aa3", "--aaindex3", action="store",type=str, dest="aa3", help="Potential aaindex3")
parser.add_argument ("-w", "--win", action="store",type=int, dest="win", help="Windows around mutation")
#parser.add_argument ("-o", "--out-file", action="store",type=str, dest="outfile", help="Output file")
#parser.add_argument ("-m", "--mutation-list",action="store_true",dest="ml", help="Mutation is parsed as a comma separated list")
parser.add_argument ("-v", "--verbose", action="store",type=int, dest="verb", help="Verbose output")
#parser.add_argument ("--outdir", "--out-dir", action="store",type=str, dest="outdir", help="Output directory")
parser.add_argument ("-d", "--db", action="store",type=str, dest="dbfile", help="DB file for hhblits")
parser.add_argument ("-s", "--search-prog", action="store",type=str, dest="hhblits", help="hhblits")
args = parser.parse_args()
aa1='KYTJ820101'
aa2='HENS920102'
aa3='SKOJ970101'
win=2
#muts={}
#sep=','
verb=0
#outdir=None
#outfile=None
#seqfile=args.seqfile
'''if os.path.isfile(seqfile)==False:
print >> sys.stderr,'ERROR: Incorrect sequence file '+seqfile+'.'
sys.exit(1)'''
if args.aa1: aa1=args.aa1
if args.aa2: aa2=args.aa2
if args.aa3: aa1=args.aa3
if args.win: win=args.win
if args.verb in [1,2]: verb=args.verb
#if args.outdir: outdir=args.outdir
#if args.outfile: outfile=args.outfile
if args.dbfile: uniclust30=args.dbfile
if args.hhblits: pblast=args.hhblits
if not os.path.isfile(pblast):
print (sys.stderr,'ERROR: hhblits program not found in',pblast)
sys.exit(4)
if not os.path.isfile(uniclust30+'_a3m_db.index'):
print (sys.stderr,'ERROR: DB file clust30_2018_08 not found in',uniclust30)
sys.exit(5)
'''if args.ml:
if parse_mut(args.mutations):
muts[sort_mut(args.mutations)]=[mut for mut in sort_mut(args.mutations).split(sep) if mut!='']
else:
if os.path.isfile(args.mutations):
lmut=open(args.mutations).read()
muts=dict((sort_mut(mut),sort_mut(mut).split(sep)) for mut in lmut.replace(' ','').split('\n') if parse_mut(mut))
if len(muts)==0:
print >> sys.stderr,'ERROR: Incorrect mutation list.'
sys.exit(2)'''
return [aa1,aa2,aa3],win,verb
def parse_mut(imut,sep=','):
v_mut=imut.split(sep)
v_pos=[]
for mut in v_mut:
c=True
try:
pos=int(mut[1:-1])
if pos in v_pos:
c=False
else:
v_pos.append(pos)
if aalist.index(mut[0])==-1 or aalist.index(mut[-1])==-1: c=False
except:
c=False
if not c:
if mut!='': print (sys.stderr,'WARNING: Incorrect mutation',imut)
break
return c
def sort_mut(imut,sep=','):
v_mut=imut.split(sep)
t_mut=[(int(j[1:-1]),j) for j in v_mut]
t_mut.sort()
return ','.join([i[1] for i in t_mut])
def ali2fasta(filein,fileout):
fb=open(filein)
vd=''
for line in fb:
v=line.rstrip().split()
vd=vd+'>'+v[0]+'\n'+v[1]+'\n'
fb.close()
fb=open(fileout,'w')
fb.write(vd)
fb.close()
def get_hssp(hsspfile):
hssp=readHSSP(hsspfile)
dhssp=hssp2dic(hssp)
return dhssp
def get_pot_res(res,pot='KYTJ820101'):
dpot=pickle.load(open(data_path+'/aaindex1.pkl')).get(pot)
return dpot.get(res,0.0)
def get_pot_prof(hsspfile,l_mut,pot='KYTJ820101'):
l_score={}
l_hssp={}
with open(data_path+'/aaindex1.pkl', 'rb') as pickle_file:
dpot = pickle.load(pickle_file, encoding='latin1').get(pot)
#dpot = cPickle.load(open(data_path+'/aaindex1.pkl')).get(pot,{})
#dpot=pickle.load(open(data_path+'/aaindex1.pkl')).get(pot,{})
if len(dpot.keys())==0:
print (sys.stderr,'Incorrect potential',pot)
return l_score
dhssp=get_hssp(hsspfile)
for i in l_mut.keys():
v_mut=l_mut[i]
v_dat=[]
v_prof=[]
for mut in v_mut:
swt=0.0
snew=0.0
wt=mut[0]
pos=int(mut[1:-1])
new=mut[-1]
prof=dhssp.get(pos,{})
if len(prof.keys())==0 or prof['WT']!=wt:
print (sys.stderr,'WARNING: Profile position',pos,'not found or incorrect residue.')
v_dat=[]
v_prof=[]
break
v_prof.append((prof[wt],prof[new]))
swt=dpot.get(wt,0.0)*prof.get(wt,0.0)*0.01
snew=dpot.get(new,0.0)*prof.get(new,0.0)*0.01
v_dat.append((swt,snew))
l_score[i]=v_dat
l_hssp[i]=v_prof
return l_score,l_hssp
def get_subs_prof(hsspfile,l_mut,pot='HENS920102'):
l_score={}
with open(data_path+'/aaindex2.pkl', 'rb') as pickle_file:
dpot = pickle.load(pickle_file, encoding='latin1').get(pot)
#dpot=cPickle.load(open(data_path+'/aaindex2.pkl')).get(pot,{})
if len(dpot.keys())==0:
print (sys.stderr,'Incorrect potential',pot)
return l_score
dhssp=get_hssp(hsspfile)
for i in l_mut.keys():
v_mut=l_mut[i]
v_dat=[]
for mut in v_mut:
swt=0.0
snew=0.0
wt=mut[0]
pos=int(mut[1:-1])
new=mut[-1]
prof=dhssp.get(pos,{})
if len(prof.keys())==0 or prof['WT']!=wt:
print (sys.stderr,'WARNING: Profile position',pos,'not found or incorrect residue.')
v_dat=[]
break
for aa in aalist:
swt=swt+dpot.get((wt,aa),0.0)*prof.get(aa,0.0)*0.01
snew=snew+dpot.get((new,aa),0.0)*prof.get(aa,0.0)*0.01
v_dat.append((swt,snew))
l_score[i]=v_dat
return l_score
def get_seq_prof(hsspfile,l_mut, w=2 ,pot='SKOJ970101'):
l_score={}
with open(data_path+'/aaindex3.pkl', 'rb') as pickle_file:
dpot = pickle.load(pickle_file, encoding='latin1').get(pot)
#dpot=pickle.load(open(data_path+'/aaindex3.pkl')).get(pot,{})
if len(dpot.keys())==0:
print (sys.stderr,'Incorrect potential',pot)
return l_score
dhssp=get_hssp(hsspfile)
n=len(dhssp.keys())
for i in l_mut.keys():
v_mut=l_mut[i]
v_dat=[]
for mut in v_mut:
swt=0.0
snew=0.0
wt=mut[0]
pos=int(mut[1:-1])
new=mut[-1]
prof=dhssp.get(pos,{})
if len(prof.keys())==0 or prof['WT']!=wt:
print (sys.stderr,'WARNING: Profile position',pos,'not found or incorrect residue.')
v_dat=[]
break
s=max(1,pos-w)
e=min(n,pos+w)
for j in [*range(s,pos), *range(pos+1,e+1)]:
iprof=dhssp.get(j,{})
for aa in aalist:
swt=swt+dpot.get((aa,wt),0.0)*iprof.get(aa,0.0)*0.01
snew=snew+dpot.get((aa,new),0.0)*iprof.get(aa,0.0)*0.01
v_dat.append((swt,snew))
l_score[i]=v_dat
return l_score
def run_seq_pipeline(seqfile,blast_prog=pblast,outdir=None,e=1e-9):
global uniclust30
if outdir:
tmpdir=outdir
rd=''
else:
tmpdir=tempfile.mkdtemp()
rd=tmpdir
seqname=seqfile.split('/')[-1]
seqname1 = seqname.split('.fasta')
seqname1 = seqname1[0]
#print(seqname1)
blastfile=tmpdir+seqname1+'11.blast'
hsspfile=tmpdir+seqname1+'11.hssp'
if os.path.isfile(blastfile)==False:
#cmd=blast_prog+' -i '+seqfile+' -d '+db+' -e '+str(e)+' -j 1 -b 1000 -v 1000 -o '+blastfile
cmd=blast_prog+' -d '+uniclust30+' -i '+seqfile+' -opsi '+blastfile+'x -n 2 -cpu 12'
print('1) Run HHBLITS Search')
print(cmd)
out=getstatusoutput(cmd)
if out[0]!=0:
blastfile=''
print ('HHBLITS_ERROR:'+out[1])
sys.exit(1)
ali2fasta(blastfile+'x',blastfile)
getstatusoutput('rm '+blastfile+'x')
if os.path.isfile(hsspfile)==False:
print(pprof)
cmd=pprof+' '+seqfile+' '+blastfile+' '+hsspfile
print('2) Generate HSSP File')
print(cmd)
out=getstatusoutput(cmd)
if out[0]!=0:
print ('HSSP_ERROR:'+out[1])
getstatusoutput('rm -r '+blastfile+' '+rd)
sys.exit(1)
return hsspfile
def get_muts_score(seqfile,hsspfile,muts,pots,win,outdir=None):
l_data={}
l_mut=muts
s_hyd,l_hssp=get_pot_prof(hsspfile,l_mut,pots[0])
s_sub=get_subs_prof(hsspfile,l_mut,pots[1])
s_pro=get_seq_prof(hsspfile,l_mut,win,pots[2])
for i in l_mut.keys():
v_mut=l_mut[i]
n=len(v_mut)
hs=s_hyd.get(i,[])
ss=s_sub.get(i,[])
ps=s_pro.get(i,[])
if len(hs)==0 or len(ss)==0 or len(ps)==0:
print (sys.stderr,'WARNING: Incorrect profile calculation for mutation',i)
continue
l_data[i]=[]
for j in range(n):
v_score=[hs[j][1]-hs[j][0],ss[j][1]-ss[j][0],ps[j][1]-ps[j][0]]
l_data[i].append(v_score)
if not outdir:
odir=os.path.dirname(hsspfile)
getstatusoutput('rm -r '+odir)
return l_data,l_hssp
def print_data(seqfile,l_data,l_hssp,verb,sep=','):
# Coefficients
#0.331 0.267 -0.328
nfile=seqfile.split('/')[-1]
s_mut=[]
out_data=[]
header='#SEQFILE\tVARIANT\tS_DDG\tT_DDG\n'
if verb==1: header='#SEQFILE\tVARIANT\t\tS_KD\tS_BL\tS_PROF\tDDG\tT_DDG\n'
if verb==2: header='#SEQFILE\tVARIANT\tCONSERVATION\tS_KD\tS_BL\tS_PROF\tDDG\tT_DDG\n'
for mut in l_data.keys():
s_mut.append([[int(i[1:-1]) for i in mut.split(sep)],mut])
s_mut.sort()
for lpos,mut in s_mut:
pm=[]
n=len(lpos)
v=[[],[],[],[]]
line='\t'.join([nfile,mut])
for j in range(n):
vm=l_data[mut][j]
return vm
def ddgun_features(seqfile, wild, mut_pos, mutant, outdir, hhblits_db):
#pots, win, verb = get_options()
global uniclust30
uniclust30 = hhblits_db
win = 2
verb = 0
aa1='KYTJ820101'
aa2='HENS920102'
aa3='SKOJ970101'
pots = [aa1,aa2,aa3]
mut_pos = str(mut_pos)
#print (seqfile, muts, pots, verb, outfile, outdir)
muts_csv = {wild+mut_pos+mutant:[wild+mut_pos+mutant]}
#for m in mut:
#muts_csv[m[0]] = [m[0]]
#print muts_csv
hsspfile=run_seq_pipeline(seqfile,pblast,outdir)
l_data,l_hssp=get_muts_score(seqfile,hsspfile,muts_csv,pots,win,outdir)
if len(l_data)==0:
print (sys.stderr,'ERROR: Incorrect mutation list.')
sys.exit()
out_data=print_data(seqfile,l_data,l_hssp,verb)
return list(out_data)