def info2seeds(N,infofile,probefile,species='YEAST'):
G = ProbeSet(species)
IDs = G.ids_from_file(probefile)
Q = EM.theMarkovBackground.zeroth()
seqs = Fasta.seqs(infofile)
if not N:
nmers = seqs
else:
nmers= MotifTools.top_nmers(N,seqs)
if len(nmers) > 1000: nmers = nmers[0:1000]
print "Scoring enrichment of %d nmers from %s"%len(nmers,infofile)
sys.stdout.flush()
nmers_scoresT = []
for nmer in nmers:
if nmer.isalpha():
p = G.p_value(nmer,IDs,'') #'verbose'
nmers_scoresT.append((nmer,p))
nmers_scoresT.sort(lambda x,y: cmp(x[1],y[1]))
last = min(20,len(nmers_scoresT))
models = []
for i in range(last):
seq = nmers_scoresT[i][0]
m = MotifTools.Motif('',Q)
m.compute_from_text(seq,0.1)
models.append(m)
for tup in nmers_scoresT[0:40]:
print tup
return(models)
def estimate_frequency(motif,k,samples=100000,thresh=0.7):
#Build sequences
estimate = -30
total = 0
totalcount = 0
for i in range(40):
long_string = 'ACGT'*(int(float(samples)*k/4))
long_string = list(long_string)
random.shuffle(long_string)
random.shuffle(long_string)
random.shuffle(long_string)
long_string = ''.join(long_string)
seqD = {}
for i in range(samples):
offset = k*i
seqD[i] = long_string[offset:offset+k]
P = ProbeSet(genome=seqD)
count = P.count_matching_probes(motif,thresh=thresh)
total += float(samples)
totalcount += float(count)
f = totalcount/total
d = math.fabs(f-estimate)/(estimate+0.00000001)
estimate = f
if d < 1e-4: break
if i > 2 and totalcount > 100: break
#print '%10d %10d %12.3e %12.3e'%(totalcount, total, f, d)
return estimate
def estimate_frequency(motif, k, samples=100000, thresh=0.7):
#Build sequences
estimate = -30
total = 0
totalcount = 0
for i in range(40):
long_string = 'ACGT' * (int(float(samples) * k / 4))
long_string = list(long_string)
random.shuffle(long_string)
random.shuffle(long_string)
random.shuffle(long_string)
long_string = ''.join(long_string)
seqD = {}
for i in range(samples):
offset = k * i
seqD[i] = long_string[offset:offset + k]
P = ProbeSet(genome=seqD)
count = P.count_matching_probes(motif, thresh=thresh)
total += float(samples)
totalcount += float(count)
f = totalcount / total
d = math.fabs(f - estimate) / (estimate + 0.00000001)
estimate = f
if d < 1e-4: break
if i > 2 and totalcount > 100: break
#print '%10d %10d %12.3e %12.3e'%(totalcount, total, f, d)
return estimate
def probOvlpBinomial(A,B,thresh=0.7,verbose=None):
if A.width >= B.width:
Wide, Narrow = A, B
else:
Wide, Narrow = B, A
RC = MotifTools.revcomplement
newWide = Wide[-1,Wide.width+1]
if Wide.__dict__.has_key('bestWide'):
bestWide = Wide.bestWide
else:
bestWideD = {}
for x in newWide.bestseqs(thresh*newWide.maxscore):
bestWideD[x[1]] = 1
for x in bestWideD.keys():
bestWideD[RC(x)] = 1
Wide.bestWide = bestWideD.keys()
bestWide = Wide.bestWide
Wide = newWide
D={}
for i in range(len(bestWide)):
D[i] = bestWide[i]
P = ProbeSet(genome=D)
matchNarrow = P.count_matching_probes(Narrow,thresh=thresh)
if matchNarrow == 0:
p = 1.0
return p
if not Narrow.__dict__.has_key('probNarrow'): Narrow.probNarrow = {}
if Narrow.probNarrow.has_key(Wide.width):
probNarrow = Narrow.probNarrow[Wide.width]
else:
probNarrow = estimate_frequency(Narrow,Wide.width,thresh=thresh)
Narrow.probNarrow[Wide.width] = probNarrow
p = Arith.binomialsumtail(probNarrow,len(bestWide),matchNarrow)
print '\nD= %7.3f %9.4e %8d %7d %-14s %-20s %-14s %-20s'%(
Arith.nlog10(p),probNarrow,len(bestWide),matchNarrow,
A.family,A,B.family,B)
return p
def probOvlpBinomial(A, B, thresh=0.7, verbose=None):
if A.width >= B.width:
Wide, Narrow = A, B
else:
Wide, Narrow = B, A
RC = MotifTools.revcomplement
newWide = Wide[-1, Wide.width + 1]
if Wide.__dict__.has_key('bestWide'):
bestWide = Wide.bestWide
else:
bestWideD = {}
for x in newWide.bestseqs(thresh * newWide.maxscore):
bestWideD[x[1]] = 1
for x in bestWideD.keys():
bestWideD[RC(x)] = 1
Wide.bestWide = bestWideD.keys()
bestWide = Wide.bestWide
Wide = newWide
D = {}
for i in range(len(bestWide)):
D[i] = bestWide[i]
P = ProbeSet(genome=D)
matchNarrow = P.count_matching_probes(Narrow, thresh=thresh)
if matchNarrow == 0:
p = 1.0
return p
if not Narrow.__dict__.has_key('probNarrow'): Narrow.probNarrow = {}
if Narrow.probNarrow.has_key(Wide.width):
probNarrow = Narrow.probNarrow[Wide.width]
else:
probNarrow = estimate_frequency(Narrow, Wide.width, thresh=thresh)
Narrow.probNarrow[Wide.width] = probNarrow
p = Arith.binomialsumtail(probNarrow, len(bestWide), matchNarrow)
print '\nD= %7.3f %9.4e %8d %7d %-14s %-20s %-14s %-20s' % (Arith.nlog10(
p), probNarrow, len(bestWide), matchNarrow, A.family, A, B.family, B)
return p
from TAMO import MotifTools from TAMO.seq import Fasta from TAMO.MotifMetrics import ProbeSet from TAMO.MD.AlignAce import AlignAce from TAMO.MD.MDscan import MDscan from TAMO.MD.Meme import Meme #from TAMO.DataSources import GO from time import time fastaPath = '/Users/biggus/Documents/James/Data/ClusterDefs/TC-Fastas/TC-96.oneLine.fas' clusterIDS = Fasta.ids(fastaPath) totalSeqs = ProbeSet(fastaPath) # !! this is wrong should proly be goodAffys MDbg = '/Users/biggus/Documents/James/Data/2KB/2kb_Sequence/2kb_Anopheles/2KBupTSS_goodAffyAGAPsFastasOUT.masked.nr.MD.bg' outFile = '/Users/biggus/Documents/James/Data/ClusterDefs/testTAMOmetrics.txt' #theAce = AlignAce(fastaPath,width=10) print 'running MDscan...' tMD_1 = time() MDmotifs = MDscan(fastaPath) #,bgfile=MDbg) tMD_2 = time() MD_time = tMD_2-tMD_1 print 'MDscan took %.5f sec == %.3f min.\nMDscan found %s motifs.' % (MD_time,MD_time/60.0, len(MDmotifs.motifs)) print 'running MEME...' tMeme_1 = time() memeMotifs = Meme(fastaPath) tMeme_2 = time() Meme_time = tMeme_2-tMeme_1
for f in pklFiles:
unPikls[f.split('/')[-1]] = pickle.load(open(f,'r'))
motifs = []
for i in unPikls:
for j in range(len(unPikls[i])):
fastaSourceName = unPikls[i][j].lines[1].split()[2].split('/')[-1]
motifs.append([fastaSourceName,unPikls[i][j].results])
# Adjust each motif to the species being looked at
for m in motifs:
for i in
motifs[i][1].new_bg(speciesBK)
probSet = ProbeSet('/Users/biggus/Documents/James/Data/2KB/2kb_Sequence/2kb_Anopheles/2KBupTSS_goodAffyAGAPsFastasOUT.masked.nr.fas')
# get and print motif and pVal(s)
out = '#outFile\tMotif\tHyperGeoPval (%s)\tfrac (%s)\tBestHG (pval)\tfrac (bestHG_ScoreThresh)\tBestHG (scoreThresh)\tbinoPval (%s)\tbinoPval (bestHG_scoreThresh)' \
% (dfltFactor,dfltFactor,dfltFactor)
print out
out = out+'\n'
for m in motifs:
for i in m[1]:
bestE = probSet.best_p_value(m[1],coRegSeqs)
temp ='%s\t%s\t%.3e\t%.3f\t%.3e\t%.3f\t%.3f\t%.3e\t%.3e' % (m[0],
m[1].oneletter,
probSet.Enrichment(m[1],coRegSeqs,factor=dfltFactor),
probSet.frac(m[1],coRegSeqs,factor=dfltFactor),
bestE[0],
from gusPyCode.MDAP_proj.MDAP_defs import transfacLike2tamoMotif
from TAMO.MotifMetrics import ProbeSet
from TAMO import MotifTools
import os
listPath = '/Users/biggus/Documents/James/Data/ReClustering/PrelimData_Grant_Feb09/kMerPWMs/Clus2_kmerSearch.6-8mers.top10pcnt/Group5.txt'
probSetReal = ProbeSet('/Users/biggus/Documents/James/Data/2KB/2kb_Sequence/2kb_Anopheles/2KBupTSS_goodAffyAGAPsFastasOUT.masked.nr.fas')
probSetShuf = ProbeSet('/Users/biggus/Documents/James/Data/2KB/2kb_Sequence/2kb_Anopheles/2KBupTSS_goodAffyAGAPsFastasOUT.masked.nr.seqsShuffled.fas')
coRegSeqs = '/Users/biggus/Documents/James/Data/ReClustering/kmedsPear33Clus50x_2/Clus2_247genes.genes.txt'
coRegSeqs = map(lambda l: l.strip(), open(coRegSeqs, 'rU').readlines())
# set real or shuffled genome
#probSet=probSetReal
motifs = map(lambda l: l.strip(), open(listPath, 'rU').readlines())
for m in range(len(motifs)):
motifs[m] = MotifTools.Motif_from_text(motifs[m])
group = 'Group5'
# calc HyperGeo for all motifs
print '#threshold = 75% of max score\n#Group\tone_letter\tpVal\tfraction_of_gene_set\tpVal (shuffled)\tfraction_of_gene_set (shuffled)'
for m in motifs:
#! /usr/bin/env python2.4 # Author: Alexandre S. Cristino # email: [email protected] # Date: 16 june 2008 # Script: Scoring motifs in upstream regions of specific databases import os,sys,string from TAMO import MotifTools from TAMO.seq import Fasta from TAMO.MotifMetrics import ProbeSet promoters = ProbeSet(sys.argv[1]) geneset_ids = open(sys.argv[2]).read().split('\n')[:-1] match_ids = [] prom_ids = promoters.probes.keys() for id in geneset_ids: if id in prom_ids: match_ids.append(id) motifs = MotifTools.load(sys.argv[3]) church = 0.05 rocauc = 0.1 pvalue = 0.05 print "Name\tMotif\tChurch\tRoc-auc\tP-value" for m in motifs: m.church = promoters.church (m, match_ids) # m.ROC_auc = promoters.ROC_AUC (m, match_ids) m.pvalue = promoters.p_value (m, match_ids)
def main():
if len(sys.argv) < 2:
print "Usage: %s <fasta_file> [width = None ] [options]"%(re.sub('^.*/','',sys.argv[0]))
print "Options include:"
print ""
print " EM Parameters:"
print " -beta [0.01] Beta for pseudocounts"
print " -seedbeta[0.02] Beta for pseudocounts for seeds from text"
print " -gamma [0.2] Gamma (fraction of sequences)"
print " -delta [0.001] Convergence criteria"
print " "
print " Seeds (not actually proper priors)"
print " -prior Seqences or motifs for seeds (may be repeated)"
print " -top N [0] Include w-mers in top N probes"
print " -gap string sample gapped motifs"
# print " -TF Seed with (all) TRANSFAC PSSMs (buggy)"
print " -kmerseeds Use kmers with best enrichment score as seeds for EM"
print " -pad add NN..NN to seed"
print " "
print " Genome / Background model "
print " -human (250,1000) Use Human Background model"
print " -g genome.fsa Use specicied Fasta file as background (searches first for matching frequency file)"
# print " -Y2K, -Y5C Use Yeast Upstream Intergenic regions (2000, 500)"
# print " -B Use Bacterial Orfs"
print " "
print "Examples:"
print " %s t.fsa 5 -prior GGGTA -prior AAAAAC "%(sys.argv[0].split('/')[-1])
print " will start an EM with 3 seeds: GGGTA, AAAAA, and AAAAC"
print
print " %s t.fsa 5 -info CUP9.info -gamma 0.5 "%(sys.argv[0].split('/')[-1])
print " will start an EM with Enriched seeds in CUP9.info, with"
print " Gamma expectation of 50% of all probes"
print
print " %s t.fsa -prior MCM1_5.tamo:0 "%(sys.argv[0].split('/')[-1])
print " will start an EM with 0th motif of the file MCM1_5.tamo"
print " as a seed"
print
sys.exit(1)
fastafile = sys.argv[1]
#Echo the command line
print "#" + ' '.join(map(lambda x: re.sub(' ','\ ',x), sys.argv))
if sys.argv[2].isdigit():
width = sys.argv[2]
else: width = None
algorithm = ''
beta = ''
seedbeta = ''
deltamin = ''
gamma = 0.2
infofile = ''
seedmodels= []
species = 'YEAST'
valid_tfs = [] #NOT USED
gapped_syl= None
gapflank = 0
gapweight = 0.2
enrichfact= 0.7
pmax = 0 #False
TFSEEDS = 0
TFMids = []
pad = None
bgfile = None
seed_count = 0 #Default: Take the top 0
seed_s = [] #Initialize seq array
'''Parse command-line arguments'''
for tok,i in zip(sys.argv,xrange(len(sys.argv))):
if tok == '-top' : seed_count = int(sys.argv[i+1])
elif tok == '-greedy': algorithm = "GREEDY"
elif tok == '-prior' : seed_s.append(sys.argv[i+1])
elif tok == '-beta' : beta = float(sys.argv[i+1])
elif tok == '-seedbeta': seedbeta = float(sys.argv[i+1])
elif tok == '-gamma' : gamma = float(sys.argv[i+1])
elif tok == '-delta' : deltamin = float(sys.argv[i+1])
elif tok == '-kmerseeds' : infofile = 1
elif tok == '-valid' : valid_tfs.append(sys.argv[i+1]) #NOT USED
elif tok == '-w' : width = sys.argv[i+1]
elif tok == '-width' : width = sys.argv[i+1]
elif tok == '-gap' : gapped_syl = sys.argv[i+1]
elif tok == '-gapflank' :gapflank = int(sys.argv[i+1])
elif tok == '-gapweight':gapweight = float(sys.argv[i+1])
elif tok == '-enrichfact':enrichfact= float(sys.argv[i+1])
elif tok == '-pmax' : pmax = 1
elif tok == '-Y2K' : species = "YEAST_2000_UP"
elif tok == '-Y5C' : species = "YEAST_500_UP"
elif tok == '-B' : species = "BAC_ORF"
elif tok == '-Ch22' : species = "Ch22"
elif tok == '-genome': species = sys.argv[i+1]
elif tok == '-pad' : pad = "TRUE"
elif tok == '-bgfile': bgfile = sys.argv[i+1]
elif tok == '-TF' : #NOT USED (TRANSFAC NOT SUPPLIED WITH DISTRIBUTION)
TFSEEDS = 1
for j in range(i+1,len(sys.argv)):
if re.match('M0',sys.argv[j]):
TFMids.append(sys.argv[j])
else:
break
elif tok == '-human' :
_s = ''
if sys.argv[i+1].isdigit(): _s = '_'+sys.argv[i+1]
else: _s = ''
species = 'HUMAN'+_s
if infofile: infofile = fastafile
if bgfile:
EM.loadMarkovBackground(bgfile)
elif not ('-random_background' in sys.argv or '-nomarkov' in sys.argv):
EM.loadMarkovBackground(species)
else:
EM.theMarkovBackground = EM.Zeroth()
fsaD = Fasta.load(fastafile)
Fasta.delN(fsaD)
seqs = fsaD.values()
probes = fsaD.keys()
all_seqs = seqs
seed_s.extend(seqs[0:min(seed_count,len(seqs))])
if infofile and width=='info':
width = info2width(infofile)
elif width != None:
width = int(width)
#Alternate source of seeds
if infofile:
if 1 or width:
seedmodels.extend(info2seeds(width,infofile,fastafile,species))
else:
print 'Error: need to specify motif width w/ .info file'
#Any -prior pointers to motifs in other files?
(seed_s, motifs) = parse_priors(seed_s)
seedmodels.extend(motifs)
#Should we get seeds from TRANSFAC?
if TFSEEDS: #NOT USED
tf = []
D = tfmats()
if not TFMids:
keys = D.keys()
else:
keys = []
for TFMid in TFMids:
for key in D.keys():
if key[0:6] == TFMid:
keys.append(key)
break
for key in keys:
m = D[key]
m.seednum = int(re.sub('M0*','',key.split()[0]))
m.seedtxt = '%-24s %s'%(m,key)
tf.append(m)
tf.sort(lambda x,y: cmp(x.seednum,y.seednum))
seedmodels.extend(tf)
#seedmodels.append(tf[33])
if gapped_syl:
gapped_priors = gapped_motifs(gapped_syl)
gapped_priors = map(lambda x:'N'+x+'N', gapped_priors)
seed_s.extend(gapped_priors)
if pad:
print '# Padding models with NN-m-NN'
newmodels = []
left = MotifTools.Motif_from_text('@')
right = MotifTools.Motif_from_text('N')
for m in seedmodels:
newmodels.append(left + m + right)
print left + m + right
seedmodels = newmodels
'''
Set everything up and GO!!
'''
global theEM
theEM = EM.EM(seed_s,[],width,"VERBOSE")
if beta: theEM.beta = beta
if deltamin: theEM.deltamin = deltamin
if seedbeta: theEM.seedbeta = seedbeta
theEM.param['gamma'] = gamma
theEM.seqs.extend(all_seqs)
theEM.models = seedmodels
theEM.gapflank = gapflank
theEM.gapweight = gapweight
theEM.report()
theEM.EM_Cstart() #GO!!
#print "#Sorting candidates"
#sys.stdout.flush()
#EM.candidates.sort(lambda x,y: cmp(y.MAP,x.MAP))
'''
Compute some metrics
'''
print "#Loading Genome %s"%species ; sys.stdout.flush()
Genome = ProbeSet(species,enrichfact)
ids = Genome.ids_from_file(fastafile)
for C in theEM.candidates:
if not pmax:
C.pssm.pvalue = Genome.p_value(C.pssm,ids,'verbose')
C.pssm.church = Genome.church(C.pssm,ids)
C.pssm.frac = Genome.frac(C.pssm,probes,None,0.7)
else:
(p,frac) = Genome.best_p_value(C.pssm,ids)
C.pssm.pvalue = p
C.pssm.threshold = frac * C.pssm.maxscore
print "Bests:",p,frac
matching = Genome.matching_ids(C.pssm,[],factor=0.7)
matchbound = [x for x in matching if x in probes]
C.pssm.numbound = len(probes)
C.pssm.nummotif = len(matching)
C.pssm.numboundmotif = len(matchbound)
sys.stdout.flush()
'''
Print out all motifs (sorted by Enrichment) in an AlignACE-like form
'''
theEM.candidates.sort(lambda x,y: cmp(x.pssm.pvalue,y.pssm.pvalue))
for C,i in zip(theEM.candidates,range(len(theEM.candidates))):
C.pssm.maxscore = -100 #May have side effects. Recompute when done
if C.pssm.valid: #NOT USED
_t = C.pssm.valid
if not _t[0]:
vstring = "(--- %8.4f %8.4f %s)"%(_t[1],_t[2],_t[3])
else:
vstring = "(HIT %8.4f %8.4f %s)"%(_t[1],_t[2],_t[3])
else:
vstring = ''
C.pssm._maxscore() #Recomputed
MotifTools.print_motif(C.pssm,20,i)
sys.stdout.flush()
continue
#Antiquated stuff -- Remove !!
print "Log-odds matrix for Motif %3d %s"%(i,C)
C.pssm._print_ll()
print "Sequence Logo"
C.pssm._print_bits()
flush()
#print '# %3d matching sequences at 90%%'%len(C.pssm.bestseqs(C.pssm.maxscore * 0.9))
flush()
m = C.pssm
if not m.__dict__.has_key('gamma'): m.gamma = None #Kludge to deal w/ old shelves
if m.seedtxt: print "Seed: %3d %s"%(i,m.seedtxt)
if m.source: print "Source: ",m.source
if m.gamma: print "Gamma: %7.5f"%m.gamma
if m.threshold: print "Threshold: %5.2f"%m.threshold
#if C.pssm.seedtxt:
# print 'Seed %3d %-25s'%(i,C.pssm.seedtxt)
if C.pssm.church != None: vstring = 'ch: %5.2f %s'%(
math.fabs(math.log(C.pssm.church)/math.log(10)), vstring)
print "Motif %3d %-25s nlog(p): %6.3f %s"%(i,C,-math.log(C.pssm.pvalue)/math.log(10),vstring)
if C.pssm.threshold:
print "Threshold: %6.3f %4.1f%%"%(
C.pssm.threshold, 100.0*C.pssm.threshold/C.pssm.maxscore)
C.pssm.maxscore = -1e100 #May have side effects. Recompute when done
for seq in C.wmers:
print seq,i,C.pssm.scan(seq)[2][0]
C.pssm._maxscore() #Recomputed
print '*'*len(seq)
print "MAP Score: %f"%C.MAP
sys.stdout.flush()
sys.stdout.flush()
sys.exit(0) #Avoid ridiculous python cleanup times
