def main(): # Parse the command line parser = OptionParser(usage = "usage: %prog [options] maf_file snp_file neutral_file window_size step_size") parser.add_option("-o", "--outfile", help = "Specify file for output") parser.add_option("-s", "--species", type = "string", default = "panTro2") parser.add_option("-b", "--build", type = "string", default = "hg18") (options, args) = parser.parse_args() if len(args) != 5: parser.error("Incorrect number of arguments") else: maf_filename = args[0] snp_filename = args[1] neutral_filename = args[2] window_size = int(args[3]) step_size = int(args[4]) if options.outfile != None: out_file = open(options.outfile, 'w') #Generate snp and neutral bitsets AR_snp_bitsets = binned_bitsets_from_file(open(snp_filename)) neutral_bitsets = binned_bitsets_from_file(open(neutral_filename)) # Generate divergence bitset from maf file AR_div_bitsets = dict() chr_lens = dict() reader = bx.align.maf.Reader( open (maf_filename) ) for block in reader: comp1 = block.get_component_by_src_start( options.build ) comp2 = block.get_component_by_src_start( options.species ) if comp1 is None or comp2 is None: continue # Chromosome, start, and stop of reference species alignment chr = comp1.src.split( '.' )[1] start = comp1.start end = comp1.end # Get or create bitset for this chromosome if chr in AR_div_bitsets: bitset = AR_div_bitsets[chr] else: bitset = AR_div_bitsets[chr] = bx.bitset.BinnedBitSet() chr_lens[chr] = comp1.get_src_size() # Iterate over text and set diverged bit pos = start for ch1, ch2 in izip( comp1.text.upper(), comp2.text.upper() ): if ch1 == '-': continue if ch2 == '-': pos += 1 continue if ch1 != ch2 and not AR_snp_bitsets[chr][pos]: bitset.set( pos ) pos += 1 # Debugging Code # for chr in AR_div_bitsets: # for pos in range(0, AR_div_bitsets[chr].size): # if AR_div_bitsets[pos]: # print >> sys.stderr, chr, pos, pos+1 # Copy div and snp bitsets nonAR_snp_bitsets = dict() for chr in AR_snp_bitsets: nonAR_snp_bitsets[chr] = bx.bitset.BinnedBitSet() nonAR_snp_bitsets[chr].ior(AR_snp_bitsets[chr]) nonAR_div_bitsets = dict() for chr in AR_div_bitsets: nonAR_div_bitsets[chr] = bx.bitset.BinnedBitSet() nonAR_div_bitsets[chr].ior(AR_div_bitsets[chr]) # Generates AR snps by intersecting with neutral intervals for chr in AR_snp_bitsets: AR_snp_bitsets[chr].iand(neutral_bitsets[chr]) # Generates AR divs by intersecting with neutral intervals for chr in AR_div_bitsets: AR_div_bitsets[chr].iand(neutral_bitsets[chr]) # Inverts the neutral intervals so now represents nonAR for chr in neutral_bitsets: neutral_bitsets[chr].invert() # Generates nonAR snps by intersecting with masked neutral intervals for chr in nonAR_snp_bitsets: nonAR_snp_bitsets[chr].iand(neutral_bitsets[chr]) # Generates nonAR divs by intersecting with masked neutral intervals for chr in nonAR_div_bitsets: nonAR_div_bitsets[chr].iand(neutral_bitsets[chr]) for chr in AR_div_bitsets: for window in range(0, chr_lens[chr] - window_size, step_size): # neutral_size = neutral_bitsets[chr].count_range(window, window_size) # if neutral_size < 9200: continue AR_snp = AR_snp_bitsets[chr].count_range(window, window_size) AR_div = AR_div_bitsets[chr].count_range(window, window_size) nonAR_snp = nonAR_snp_bitsets[chr].count_range(window, window_size) nonAR_div = nonAR_div_bitsets[chr].count_range(window, window_size) if nonAR_snp >= 6 and nonAR_div >= 6 and AR_snp >= 6 and AR_div >= 6: MK_pval = MK_chi_pvalue(nonAR_snp, nonAR_div, AR_snp, AR_div) else: MK_pval = MK_fisher_pvalue(nonAR_snp, nonAR_div, AR_snp, AR_div) if options.outfile != None: out_file.write("%s\t%d\t%d\t%d\t%d\t%d\t%d\t%1.15f\n" % (chr, window, window+window_size, nonAR_snp, nonAR_div, AR_snp, AR_div, MK_pval)) else: print "%s\t%d\t%d\t%d\t%d\t%d\t%d\t%1.15f" % (chr, window, window+window_size, nonAR_snp, nonAR_div, AR_snp, AR_div, MK_pval) if options.outfile != None: out_file.close()