#switch is redundant here, can deduce from var_list type

def __init__(self, switch) :

self.switch = switch.lower()

Annotator.__init__(self, "sift" )

self.input_file = "%s/input/%s.csv" % (self.root_dir,switch)

self.output_dir = "%s/output" % (self.root_dir)

self.indexOf = {"coordinates" : 0, \

"codons" : 1, \

"transcript id" : 2, \

"protein id" : 3, \

"substitutions" : 4, \

"region" : 5, \

"dbsnp id" : 6, \

"snp type" : 7, \

"prediction" : 8, \

"score" : 9, \

"median info" : 10, \

"# seqs at position" : 11, \

"gene id" : 12, \

"gene name" : 13, \

"gene desc" : 14, \

"omim disease" : 15, \

"average allele freqs" : 16, \

"ceu allele freqs" : 17, \

"user comment" : 18}

self.cols = ["region","snp type", "prediction","score","omim disease"]

self.db_cols = ["sift_region","sift_type","sift_prediction","sift_score","sift_omim"]

def parse( self, varList ) :

if self.switch == 'snp' or self.switch == 'indel' :

if os.path.isfile( self.input_file ) :

print "There is already an input file for SIFT @ %s. ?Date?" + \

" This (probably) means SIFT has already be run" + \

" and these existing annotations can be merged." + \

" Would you like to skip to the merge step (s)" + \

" or re-run SIFT (r) ?"

uin = raw_input()

if uin.lower() == 's' :

return True

fout = open( self.input_file, 'wb' )

if self.switch == 'snp' :

for snp in varList.iterate() :

keys = ["chrom","pos","ref","mut","strand"]

values = [snp.fields[k] for k in keys]

(chrom,pos,ref,mut,strand) = values

if strand : strand = 1

else : strand = -1

fout.write( "%s,%s,%d,%s/%s\n" % (chrom,pos,strand,ref,mut) )

else :

for var in varList.iterate() :

keys = ["chrom","pos","ref","mut","strand"]

values = [var.fields[k] for k in keys]

print values

(chrom,pos,ref,mut,strand) = values

if strand : strand = 1

else : strand = -1

isInsertion = len(ref) == 1 and len(mut) > 1

isDeletion = len(ref) > 1 and len(mut) == 1

if isInsertion :

start = int(pos)

end = start

allele = mut

elif isDeletion :

start = int(pos)

end = start + (len(ref)-len(mut))

allele = '-/'

else : assert False

fout.write("%s,%d,%d,%d,%s\n" % (chrom,start,end,strand,allele) )

fout.close()

else : raise Exception("switch should be 'snp' or 'indel'")

return False

##SOMETHING IS EVER SO SLIGHTLY OFF IN TRITON BATCH SCRIPT

def run(self, i="", o="", args={'run_locally':True}) :

if not i : i = self.input_file

if not o : o = self.output_dir

run_locally = args['run_locally']

#-i : input

#-o : output

#-d : variation db directory

#-c : coding info directory

snp_exec = "./SIFT_exome_nssnvs.pl" #% (globes.SIFT_BIN)

snp_exec_and_args = [ snp_exec, \

'-i', i, \

'-o', o, \

'-d', \

'%s/db/Human_db_37' % (globes.SIFT_HOME), \

'-A', '1', \

'-B', '1', \

'-C', '1', \

'-J', '1', \

'-K', '1', \

'-L', '1']

indel_exec = ['perl', "%s/SIFT_exome_indels.pl" % (globes.SIFT_BIN)]

indel_exec_and_args = \

indel_exec + \

['-i', i, \

'-o', o, \

'-c', \

'%s/coding_info/Homo_sapien_37' % (globes.SIFT_HOME), \

'-d', \

'%s/db/Human_db_37' % (globes.SIFT_HOME) ]

#choose which version to run

if self.switch == 'snp' :

exec_and_args = snp_exec_and_args

else :

exec_and_args = indel_exec_and_args

if run_locally :

pop = subprocess.Popen(

exec_and_args, \

stdout = open( "%s/stdout" % globes.SIFT_OUTPUT, 'wb' ), \

stderr = open( "%s/stderr"% globes.SIFT_OUTPUT, 'wb' ) )

pop.wait()

else :

params = {'out' : 'sift_out.txt' , \

'err' : 'sift_err.txt' }

commands = ['cd %s' % globes.SIFT_BIN, ' '.join( exec_and_args )]

batchJob = batch.writeBatchFile( "sift_%s.csh" % self.switch, commands )

batchJob.submit()

#check output file by getting jobid, using that to check outpage

#for status 'complete'. Then can check every X seconds to move on once complete. OR, just leave this up to user, and separate merge as standalone to be invoked once output is generated, will have to do this for SS anyway

def clean( self, value ) :

if value == 'N/A' : return ''

elif value.startswith('DAMAGING') : return 'DAMAGING'

def varListComparator( self, snp, out_splt ) :

(chrom1,pos1,ref1,mut1) = snp.getPosition()

coord = out_splt[ self.indexOf["coordinates"] ].split(',')

(chrom2,pos2,strand,refmut) = coord

(ref2,mut2) = refmut.split('/')

return globes.comparePositions( chrom1,pos1,chrom2,pos2 )

#return globes.compareVariants( chrom1,pos1,ref1,mut1,\

#chrom2,pos2,ref2,mut2 )

def varListIntegrator( self, snp, out_splt ) :

for (c,dbc) in zip(self.cols,self.db_cols) :

snp.fields[dbc] = self.clean( out_splt[self.indexOf[c]] )

def sqlComparator( self, sqlrow, out_splt ) :

(chrom1,pos1,ref1,mut1) = sqlrow[1], sqlrow[2],sqlrow[3],sqlrow[4]

coord = out_splt[ self.indexOf["coordinates"] ].split(',')

(chrom2,pos2,strand,refmut) = coord

(ref2,mut2) = refmut.split('/')

return globes.compareVariants( chrom1,pos1,ref1,mut1,\

chrom2,pos2,ref2,mut2 )

def sqlIntegrator( self, sqlrow, out_splt ) :

(eyeD,chrom,pos,ref,mut,gene_id) = sqlrow

##update the gene with any information

#q = "select name from Genes where id = %d" % gene_id

#name = self.conn.query( q )[0][0]

#if not name :

#values = (out_splt[ self.indexOf["Gene Name"] ])

#columns = ("name")

#self.conn.update("Genes", values, columns, gene_id)

#update variant

#don't really need 'snp type' as the ref/mut AA imply it

values = [out_splt[ self.indexOf[c] ] for c in self.cols]

try : float(values[3])

except ValueError : values[3] = 'NULL'

self.conn.update("Variants", values, self.db_cols, eyeD)

pass

def register( self, dargs ) :

prediction_num = dargs["prediction"]

predictions_file = "%s/%d/%d_predictions.tsv" \

% (globes.SIFT_OUTPUT, \

prediction_num, \

prediction_num)

predictions_file = sort( predictions_file )

self.iterator = globes.splitIterator( predictions_file, stopper=globes.tritonStop )

#the default interaction will be with a varList

self.comp = self.varListComparator

self.eqfunc = self.varListIntegrator

self.ltfunc = doNothing

self.gtfunc = doNothing

#If merging into a SQL iterator (iSQL), then will need to be passed a db

#connection in the arg list

k = "dbconn"

if k in dargs :

self.conn = dargs[k]

self.comp = self.sqlComparator

fin = open( sift_file, 'rb' )

sorted_filename = "%s.sorted" % sift_file

fout = open( sorted_filename, 'wb' )

fout.write( "".join( sorted( fin.readlines()[1:], key = sortHelper ) ) )

fout.close()

fin = open( globes.SNP_FILE )

fout = open( "%s/intermediate_data/sift/input/sift_snp_input.csv" \

% (globes.DATA_DIR), 'wb' )

fout.close()

print indel_file

fin = open( indel_file )

(path,ext) = indel_file.split('.',1)

fname = path.split('/')[-1]

fout = open( "%s/intermediate_data/sift/input/%s_sift_input.csv" \

% (globes.DATA_DIR, fname), 'wb' )

print fout

#fast-forward through header lines

patients = broad.getPatients( fin )

indexOf = broad.COLUMN_MAP

for dataline in fin :

splt = dataline.strip().split('\t')

col_keys = ['chrom','pos','mut','ref']

chrom,pos,mut,ref = [ splt[ indexOf[k] ] for k in col_keys ]

dinfo = broad.makeInfoDict( splt[ indexOf["info"] ] )

try :

strand = dinfo["refseq.transcriptStrand"]

except KeyError :

try :

strand = dinfo["refseq.transcriptStrand_1"]

except KeyError : #dont have it guess '+'

strand = '+'

##raise Exception("what the fuck: %s" % splt[ indexOf["info"] ] )

if strand == "+" : strand = 1

elif strand == "-" : strand = -1

else : raise Exception("Strand is not + or - ??")

isInsertion = len(ref) == 1 and len(mut) > 1

isDeletion = len(ref) > 1 and len(mut) == 1

if isInsertion :

start = int(pos)

end = start

allele = mut

elif isDeletion :

start = int(pos)

end = start + (len(ref)-len(mut))

allele = '-/'

else : assert False

fout.write( "%s,%d,%d,%d,%s\n" % (chrom,start,end,strand,allele) )

fout.close()

if switch.lower() == "snp" :

if run_locally :

sift = "%s/SIFT_exome_nssnvs.pl" % (globes.SIFT_BIN)

#-i : input

#-o : output

#-d : variation db directory

#-c : coding info directory

pop = subprocess.Popen(

[sift, \

'-i', \

'%s/%s.csv' % (globes.SIFT_INPUT, input_filename), \

'-o', \

'%s/sift_snp_output.csv'% (globes.SIFT_OUTPUT), \

'-d', \

'%s/db/Human_db_37' % (globes.SIFT_HOME), \

'-A', '1', \

'-B', '1', \

'-C', '1', \

'-J', '1', \

'-K', '1', \

'-L', '1'], \

stdout = open( "%s/stdout" % globes.SIFT_OUTPUT, 'wb' ), \

stderr = open( "%s/stderr"% globes.SIFT_OUTPUT, 'wb' ) )

pop.wait()

else :

print "remember the filename doesn't matter, you need to be targeting the correct input file @ /home/aheiberg/andrew/batch/sift_snps.csh"

pop = subprocess.Popen( \

["qsub", "/home/aheiberg/andrew/batch/sift_snps.csh"]

)

elif switch.lower() == "indel" :

sift_exec = "%s/SIFT_exome_indels.pl" % (globes.SIFT_BIN)

print sift_exec

pop = subprocess.Popen(

[sift_exec, \

'-i', \

'%s' % (input_filename), \

'-o', \

'%s' % (globes.SIFT_OUTPUT), \

'-c', \

'%s/coding_info/Homo_sapien_37' % (globes.SIFT_HOME), \

'-d', \

'%s/db/Human_db_37' % (globes.SIFT_HOME), \

], \

stdout = open( "%s/stdout" % globes.SIFT_OUTPUT, 'wb' ), \

stderr = open( "%s/stderr" % globes.SIFT_OUTPUT, 'wb' ))

pop.wait()

else :

print "Inputting SIFT: %s" % sift_file

name = globes.ROOT_DIR + globes.PLATE_NAME + \

"intermediate_files/sift/output/%d_predictions.txt.sorted"

#if cant_find :

#take the steps

fin = open( name, 'rb' )

expected_columns = 24

header = fin.readline()

assert( len( header.split("\t") ) == expected_columns )

indexOf = {"coords" : 0,

"dbSNP" : 5,

"SIFT" : 8,

"SIFTProb" : 9,

"GeneName" : 13,

"OMIM" : 21}

printColumnWarning( sift_file, indexOf )

def lineAndListMatch( j ) :

return chrom == SNPList[j].chrom and \

int(loc) == SNPList[j].genomicLoc

j = 0

for line in fin.readlines() :

splt = line.strip().split('\t')

[chrom,line,loc,aa] = splt[ indexOf["coords"] ].split(',')

#move down the SNPList until it matches the current line

while lineAndListMatch( j ) : j += 1

if j < len(SNPList) : #and lineAndListMatch(j) :

dbSNP = splt[ indexOf["dbSNP"] ]

#what about novel and ENSSNPxxxxx?

new_dbSNP_info = SNPList[j].dbSNP == "." and \

dbsnp.startswith("rs")

if new_dbSNP_info :

SNPList[j].dbSNP = justDigitsFromDBSNP( dbSNP )

SNPList[j].SIFT = splt[ indexOf["SIFT"] ]

SNPList[j].SIFTProb = float( splt[ indexOf["SIFTProb"] ] )

geneName = splt[ indexOf["GeneName"] ]

OMIM = splt[ indexOf["OMIM"] ]

if geneName :

if geneName == SNPList[j].geneName :

SNPList[j].fullName = geneName

SNPList[j].OMIM = OMIM

else :

SNPList[j].OMIM = "%s (%s?)" % (OMIM,geneName)

j += 1

while entrySameAsLast( SNPList, j ) :

SNPList[j].dbSNP = SNPList[j-1].dbSNP;

SNPList[j].SIFT = SNPList[j-1].SIFT;

#not SIFTProb as well??

SNPList[j].fullName = SNPList[j-1].fullName;

SNPList[j].OMIM = OMIM

j += 1

else :