| 1 | #!/usr/bin/python2.6 |
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| 2 | |
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| 3 | """ |
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| 4 | 'Tile' the blocks of a maf file over each of a set of intervals. The |
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| 5 | highest scoring block that covers any part of a region will be used, and |
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| 6 | pieces not covered by any block filled with "-" or optionally "*". |
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| 7 | |
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| 8 | This version uses synteny annotation if found on the alignment blocks, and |
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| 9 | will attempt to fill gaps with special characters depending on the type of |
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| 10 | gap, similar to the projected alignment display of the UCSC genome browser: |
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| 11 | '*' for new, '=' for inverse/inset, '#' for contig, 'X' for missing. |
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| 12 | |
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| 13 | - The list of species to tile is specified by the first argument (either a |
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| 14 | newick tree or just a comma separated list). |
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| 15 | |
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| 16 | - The `seq_db` is a lookup table mapping species and chromosome names |
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| 17 | to nib file for filling in the reference species sequence. In this file |
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| 18 | column 1 contains the species, column 2 the chromomsome or contig, and |
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| 19 | column 4 the directory containing the sequences in nib format. |
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| 20 | |
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| 21 | - The remaining arguments are a list of maf files which must have |
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| 22 | corresponding ".index" files. |
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| 23 | |
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| 24 | TODO: The seq_db format is specific to something old and obsure at PSU, |
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| 25 | need to standardize. |
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| 26 | |
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| 27 | usage: %prog list,of,species,to,keep seq_db_file indexed_maf_files ... |
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| 28 | -m, --missingData: Inserts wildcards for missing block rows instead of '-' |
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| 29 | -s, --strand: Use strand information for intervals, reveres complement if '-' |
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| 30 | """ |
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| 31 | |
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| 32 | import psyco_full |
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| 33 | |
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| 34 | from cookbook import doc_optparse |
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| 35 | |
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| 36 | import operator |
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| 37 | |
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| 38 | import bx.align.maf as maf |
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| 39 | import bx.align as align |
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| 40 | from bx import misc |
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| 41 | import bx.seq.nib |
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| 42 | import os |
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| 43 | import string |
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| 44 | import sys |
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| 45 | |
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| 46 | tree_tx = string.maketrans( "(),", " " ) |
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| 47 | |
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| 48 | def main(): |
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| 49 | |
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| 50 | options, args = doc_optparse.parse( __doc__ ) |
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| 51 | try: |
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| 52 | sources = args[0].translate( tree_tx ).split() |
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| 53 | seq_db = load_seq_db( args[1] ) |
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| 54 | index = maf.MultiIndexed( args[2:] ) |
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| 55 | |
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| 56 | out = maf.Writer( sys.stdout ) |
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| 57 | missing_data = bool(options.missingData) |
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| 58 | use_strand = bool(options.strand) |
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| 59 | except: |
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| 60 | doc_optparse.exception() |
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| 61 | |
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| 62 | for line in sys.stdin: |
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| 63 | fields = line.split() |
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| 64 | ref_src, start, end = fields[0:3] |
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| 65 | if use_strand and len( fields ) > 5: |
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| 66 | strand = fields[5] |
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| 67 | else: |
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| 68 | strand = '+' |
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| 69 | do_interval( sources, index, out, ref_src, int( start ), int( end ), seq_db, missing_data, strand ) |
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| 70 | |
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| 71 | out.close() |
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| 72 | |
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| 73 | def load_seq_db( fname ): |
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| 74 | db = {} |
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| 75 | for line in open( fname ): |
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| 76 | fields = line.split(',') |
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| 77 | src = fields[1] + "." + fields[2] |
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| 78 | seq = fields[4] |
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| 79 | db[src]=seq.strip() |
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| 80 | return db |
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| 81 | |
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| 82 | def get_fill_char( maf_status ): |
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| 83 | """ |
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| 84 | Return the character that should be used to fill between blocks |
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| 85 | having a given status |
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| 86 | """ |
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| 87 | ## assert maf_status not in ( maf.MAF_CONTIG_NESTED_STATUS, maf.MAF_NEW_NESTED_STATUS, |
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| 88 | ## maf.MAF_MAYBE_NEW_NESTED_STATUS ), \ |
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| 89 | ## "Nested rows do not make sense in a single coverage MAF (or do they?)" |
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| 90 | if maf_status in ( maf.MAF_NEW_STATUS, maf.MAF_MAYBE_NEW_STATUS, |
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| 91 | maf.MAF_NEW_NESTED_STATUS, maf.MAF_MAYBE_NEW_NESTED_STATUS ): |
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| 92 | return "*" |
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| 93 | elif maf_status in ( maf.MAF_INVERSE_STATUS, maf.MAF_INSERT_STATUS ): |
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| 94 | return "=" |
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| 95 | elif maf_status in ( maf.MAF_CONTIG_STATUS, maf.MAF_CONTIG_NESTED_STATUS ): |
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| 96 | return "#" |
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| 97 | elif maf_status == maf.MAF_MISSING_STATUS: |
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| 98 | return "X" |
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| 99 | else: |
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| 100 | raise "Unknwon maf status" |
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| 101 | |
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| 102 | def guess_fill_char( left_comp, right_comp ): |
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| 103 | """ |
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| 104 | For the case where there is no annotated synteny we will try to guess it |
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| 105 | """ |
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| 106 | # No left component, obiously new |
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| 107 | return "*" |
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| 108 | # First check that the blocks have the same src (not just species) and |
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| 109 | # orientation |
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| 110 | if ( left_comp.src == right_comp.src and left_comp.strand != right_comp.strand ): |
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| 111 | # Are they completely contiguous? Easy to call that a gap |
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| 112 | if left_comp.end == right_comp.start: |
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| 113 | return "-" |
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| 114 | # TODO: should be able to make some guesses about short insertions |
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| 115 | # here |
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| 116 | # All other cases we have no clue about |
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| 117 | return "*" |
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| 118 | |
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| 119 | def remove_all_gap_columns( texts ): |
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| 120 | """ |
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| 121 | Remove any columns containing only gaps from alignment texts |
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| 122 | """ |
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| 123 | seqs = [ list( t ) for t in texts ] |
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| 124 | i = 0 |
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| 125 | text_size = len( texts[0] ) |
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| 126 | while i < text_size: |
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| 127 | all_gap = True |
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| 128 | for seq in seqs: |
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| 129 | if seq[i] not in ( '-', '#', '*', '=', 'X', '@' ): |
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| 130 | all_gap = False |
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| 131 | if all_gap: |
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| 132 | for seq in seqs: |
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| 133 | del seq[i] |
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| 134 | text_size -= 1 |
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| 135 | else: |
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| 136 | i += 1 |
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| 137 | return [ ''.join( s ) for s in seqs ] |
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| 138 | |
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| 139 | def do_interval( sources, index, out, ref_src, start, end, seq_db, missing_data, strand ): |
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| 140 | """ |
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| 141 | Join together alignment blocks to create a semi human projected local |
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| 142 | alignment (small reference sequence deletions are kept as supported by |
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| 143 | the local alignment). |
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| 144 | """ |
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| 145 | ref_src_size = None |
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| 146 | # Make sure the reference component is also the first in the source list |
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| 147 | assert sources[0].split('.')[0] == ref_src.split('.')[0], "%s != %s" \ |
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| 148 | % ( sources[0].split('.')[0], ref_src.split('.')[0] ) |
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| 149 | # Determine the overall length of the interval |
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| 150 | base_len = end - start |
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| 151 | # Counter for the last reference species base we have processed |
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| 152 | last_stop = start |
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| 153 | # Rows in maf blocks come in in arbitrary order, we'll convert things |
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| 154 | # to the destred order of the tiled block |
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| 155 | source_to_index = dict( ( name, i ) for ( i, name ) in enumerate( sources ) ) |
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| 156 | # This gets all the maf blocks overlapping our interval of interest |
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| 157 | # NOTE: Unlike maf_tile we're expecting |
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| 158 | # things to be single coverage in the reference species, so we won't |
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| 159 | # sort by score and lay down. |
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| 160 | blocks = index.get( ref_src, start, end ) |
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| 161 | # The last component seen for each species onto which we are tiling |
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| 162 | last_components = [ None ] * len( sources ) |
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| 163 | last_status = [ None ] * len( sources ) |
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| 164 | cols_needing_fill = [ 0 ] * len( sources ) |
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| 165 | # The list of strings in which we build up the tiled alignment |
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| 166 | tiled_rows = [ "" for i in range( len( sources ) ) ] |
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| 167 | # Enumerate the (ordered) list of blocks |
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| 168 | for i, block in enumerate( blocks ): |
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| 169 | # Check for overlap in reference species |
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| 170 | ref = block.get_component_by_src_start( ref_src ) |
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| 171 | if ref.start < last_stop: |
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| 172 | if ref.end < last_stop: |
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| 173 | continue |
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| 174 | block = block.slice_by_component( ref, last_stop, min( end, ref.end ) ) |
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| 175 | ref = block.get_component_by_src_start( ref_src ) |
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| 176 | block = block.slice_by_component( ref, max( start, ref.start ), min( end, ref.end ) ) |
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| 177 | ref = block.get_component_by_src_start( ref_src ) |
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| 178 | # print block |
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| 179 | assert last_components[0] is None or ref.start >= last_components[0].end, \ |
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| 180 | "MAF must be sorted and single coverage in reference species!" |
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| 181 | assert ref.strand == "+", \ |
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| 182 | "MAF must have all reference species blocks on the plus strand" |
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| 183 | # Store the size of the reference sequence for building fake block |
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| 184 | if ref_src_size is None: |
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| 185 | ref_src_size = ref.src_size |
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| 186 | # Handle the reference component seperately, it has no synteny status |
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| 187 | # but we will try to fill in missing sequence |
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| 188 | if ref.start > last_stop: |
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| 189 | # Need to fill in some reference sequence |
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| 190 | chunk_len = ref.start - last_stop |
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| 191 | text = bx.seq.nib.NibFile( open( seq_db[ ref_src ] ) ).get( last_stop, chunk_len ) |
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| 192 | tiled_rows[0] += text |
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| 193 | for source in sources[1:]: |
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| 194 | cols_needing_fill[ source_to_index[ source ] ] += chunk_len |
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| 195 | # Do reference component |
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| 196 | chunk_len = len( ref.text ) |
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| 197 | tiled_rows[0] += ref.text |
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| 198 | # Do each other component |
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| 199 | for source in sources[1:]: |
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| 200 | source_index = source_to_index[ source ] |
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| 201 | comp = block.get_component_by_src_start( source ) |
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| 202 | if comp: |
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| 203 | if comp.synteny_left is None: |
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| 204 | left_status, left_length = None, -1 |
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| 205 | else: |
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| 206 | left_status, left_length = comp.synteny_left |
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| 207 | if comp.synteny_right is None: |
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| 208 | right_status, right_length = None, -1 |
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| 209 | else: |
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| 210 | right_status, right_length = comp.synteny_right |
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| 211 | # We have a component, do we need to do some filling? |
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| 212 | cols_to_fill = cols_needing_fill[ source_index ] |
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| 213 | if cols_to_fill > 0: |
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| 214 | # Adjacent components should have matching status |
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| 215 | ## assert last_status[ source_index ] is None or last_status[ source_index ] == left_status, \ |
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| 216 | ## "left status (%s) does not match right status (%s) of last component for %s" \ |
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| 217 | ## % ( left_status, last_status[ source_index ], source ) |
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| 218 | if left_status is None: |
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| 219 | fill_char = guess_fill_char( last_components[source_index], comp ) |
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| 220 | else: |
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| 221 | fill_char = get_fill_char( left_status ) |
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| 222 | tiled_rows[ source_index ] += ( fill_char * cols_to_fill ) |
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| 223 | cols_needing_fill[ source_index ] = 0 |
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| 224 | # Okay, filled up to current position, now append the text |
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| 225 | tiled_rows[ source_index ] += comp.text |
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| 226 | assert len( tiled_rows[ source_index ] ) == len( tiled_rows[ 0 ] ), \ |
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| 227 | "length of tiled row should match reference row" |
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| 228 | last_components[ source_index ] = comp |
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| 229 | last_status[ source_index ] = right_status |
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| 230 | else: |
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| 231 | # No component, we'll have to fill this region when we know |
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| 232 | # the status |
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| 233 | cols_needing_fill[ source_index ] += chunk_len |
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| 234 | last_stop = ref.end |
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| 235 | # No more components, clean up the ends |
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| 236 | if last_stop < end: |
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| 237 | # Need to fill in some reference sequence |
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| 238 | chunk_len = end - last_stop |
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| 239 | tiled_rows[0] += bx.seq.nib.NibFile( open( seq_db[ ref_src ] ) ).get( last_stop, chunk_len ) |
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| 240 | for source in sources[1:]: |
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| 241 | cols_needing_fill[ source_to_index[ source ] ] += chunk_len |
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| 242 | # Any final filling that needs to be done? |
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| 243 | for source in sources[1:]: |
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| 244 | source_index = source_to_index[ source ] |
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| 245 | fill_needed = cols_needing_fill[ source_index ] |
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| 246 | if fill_needed > 0: |
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| 247 | if last_components[ source_index ] is None: |
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| 248 | # print >>sys.stderr, "Never saw any components for %s, filling with @" % source |
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| 249 | fill_char = '@' |
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| 250 | else: |
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| 251 | if last_status[ source_index ] is None: |
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| 252 | fill_char = '*' |
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| 253 | else: |
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| 254 | fill_char = get_fill_char( last_status[ source_index ] ) |
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| 255 | tiled_rows[ source_index ] += fill_char * fill_needed |
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| 256 | assert len( tiled_rows[ source_index ] ) == len( tiled_rows[ 0 ] ), \ |
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| 257 | "length of tiled row should match reference row" |
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| 258 | # Okay, now make up the fake alignment from the tiled rows. |
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| 259 | tiled_rows = remove_all_gap_columns( tiled_rows ) |
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| 260 | a = align.Alignment() |
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| 261 | for i, name in enumerate( sources ): |
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| 262 | text = "".join( tiled_rows[i] ) |
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| 263 | size = len( text ) - text.count( "-" ) |
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| 264 | if i == 0: |
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| 265 | if ref_src_size is None: ref_src_size = bx.seq.nib.NibFile( open( seq_db[ ref_src ] ) ).length |
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| 266 | c = align.Component( ref_src, start, end-start, "+", ref_src_size, text ) |
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| 267 | else: |
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| 268 | c = align.Component( name + ".fake", 0, size, "?", size, text ) |
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| 269 | a.add_component( c ) |
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| 270 | if strand == '-': |
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| 271 | a = a.reverse_complement() |
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| 272 | out.write( a ) |
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| 273 | |
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| 274 | main() |
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