--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/bedutil.py	Mon Jan 22 13:59:27 2018 -0500
@@ -0,0 +1,515 @@
+#!/usr/bin/env python
+"""
+#
+#------------------------------------------------------------------------------
+#                         University of Minnesota
+#         Copyright 2016, Regents of the University of Minnesota
+#------------------------------------------------------------------------------
+# Author:
+#
+#  James E Johnson
+#
+#------------------------------------------------------------------------------
+"""
+
+from __future__ import print_function
+
+import sys
+
+from Bio.Seq import reverse_complement, translate
+
+
+def bed_from_line(line, ensembl=False, seq_column=None):
+    fields = line.rstrip('\r\n').split('\t')
+    if len(fields) < 12:
+        return None
+    (chrom, chromStart, chromEnd, name, score, strand,
+     thickStart, thickEnd, itemRgb,
+     blockCount, blockSizes, blockStarts) = fields[0:12]
+    bed_entry = BedEntry(chrom=chrom, chromStart=chromStart, chromEnd=chromEnd,
+                         name=name, score=score, strand=strand,
+                         thickStart=thickStart, thickEnd=thickEnd,
+                         itemRgb=itemRgb,
+                         blockCount=blockCount,
+                         blockSizes=blockSizes.rstrip(','),
+                         blockStarts=blockStarts.rstrip(','))
+    if seq_column is not None and -len(fields) <= seq_column < len(fields):
+        bed_entry.seq = fields[seq_column]
+    if ensembl and len(fields) >= 20:
+        bed_entry.second_name = fields[12]
+        bed_entry.cds_start_status = fields[13]
+        bed_entry.cds_end_status = fields[14]
+        bed_entry.exon_frames = fields[15].rstrip(',')
+        bed_entry.biotype = fields[16]
+        bed_entry.gene_name = fields[17]
+        bed_entry.second_gene_name = fields[18]
+        bed_entry.gene_type = fields[19]
+    return bed_entry
+
+
+def as_int_list(obj):
+    if obj is None:
+        return None
+    if isinstance(obj, list):
+        return [int(x) for x in obj]
+    elif isinstance(obj, str):
+        return [int(x) for x in obj.split(',')]
+    else:  # python2 unicode?
+        return [int(x) for x in str(obj).split(',')]
+
+
+class BedEntry(object):
+    def __init__(self, chrom=None, chromStart=None, chromEnd=None,
+                 name=None, score=None, strand=None,
+                 thickStart=None, thickEnd=None, itemRgb=None,
+                 blockCount=None, blockSizes=None, blockStarts=None):
+        self.chrom = chrom
+        self.chromStart = int(chromStart)
+        self.chromEnd = int(chromEnd)
+        self.name = name
+        self.score = int(score) if score is not None else 0
+        self.strand = '-' if str(strand).startswith('-') else '+'
+        self.thickStart = int(thickStart) if thickStart else self.chromStart
+        self.thickEnd = int(thickEnd) if thickEnd else self.chromEnd
+        self.itemRgb = str(itemRgb) if itemRgb is not None else r'100,100,100'
+        self.blockCount = int(blockCount)
+        self.blockSizes = as_int_list(blockSizes)
+        self.blockStarts = as_int_list(blockStarts)
+        self.second_name = None
+        self.cds_start_status = None
+        self.cds_end_status = None
+        self.exon_frames = None
+        self.biotype = None
+        self.gene_name = None
+        self.second_gene_name = None
+        self.gene_type = None
+        self.seq = None
+        self.cdna = None
+        self.pep = None
+        # T26C
+        self.aa_change = []
+        # p.Trp26Cys g.<pos><ref>><alt> # g.1304573A>G
+        self.variants = []
+
+    def __str__(self):
+        return '%s\t%d\t%d\t%s\t%d\t%s\t%d\t%d\t%s\t%d\t%s\t%s' % (
+            self.chrom, self.chromStart, self.chromEnd,
+            self.name, self.score, self.strand,
+            self.thickStart, self.thickEnd, str(self.itemRgb), self.blockCount,
+            ','.join([str(x) for x in self.blockSizes]),
+            ','.join([str(x) for x in self.blockStarts]))
+
+    def get_splice_junctions(self):
+        splice_juncs = []
+        for i in range(self.blockCount - 1):
+            splice_junc = "%s:%d_%d"\
+                % (self.chrom,
+                   self.chromStart + self.blockSizes[i],
+                   self.chromStart + self.blockStarts[i+1])
+            splice_juncs.append(splice_junc)
+        return splice_juncs
+
+    def get_exon_seqs(self):
+        if not self.seq:
+            return None
+        exons = []
+        for i in range(self.blockCount):
+            exons.append(self.seq[self.blockStarts[i]:self.blockStarts[i]
+                         + self.blockSizes[i]])
+        if self.strand == '-':  # reverse complement
+            exons.reverse()
+            for i, s in enumerate(exons):
+                exons[i] = reverse_complement(s)
+        return exons
+
+    def get_spliced_seq(self, strand=None):
+        if not self.seq:
+            return None
+        seq = ''.join(self.get_exon_seqs())
+        if strand and self.strand != strand:
+            seq = reverse_complement(seq)
+        return seq
+
+    def get_cdna(self):
+        if not self.cdna:
+            self.cdna = self.get_spliced_seq()
+        return self.cdna
+
+    def get_cds(self):
+        cdna = self.get_cdna()
+        if cdna:
+            if self.chromStart == self.thickStart\
+               and self.chromEnd == self.thickEnd:
+                return cdna
+            pos = [self.cdna_offset_of_pos(self.thickStart),
+                   self.cdna_offset_of_pos(self.thickEnd)]
+            if 0 <= min(pos) <= max(pos) <= len(cdna):
+                return cdna[min(pos):max(pos)]
+        return None
+
+    def set_cds(self, cdna_start, cdna_end):
+        cdna_len = sum(self.blockSizes)
+        if 0 <= cdna_start < cdna_end <= cdna_len:
+            cds_pos = [self.pos_of_cdna_offet(cdna_start),
+                       self.pos_of_cdna_offet(cdna_end)]
+            if all(cds_pos):
+                self.thickStart = min(cds_pos)
+                self.thickEnd = max(cds_pos)
+            return self
+        return None
+
+    def trim_cds(self, basepairs):
+        if self.chromStart <= self.thickStart < self.thickEnd <= self.chromEnd:
+            cds_pos = [self.cdna_offset_of_pos(self.thickStart),
+                       self.cdna_offset_of_pos(self.thickEnd)]
+            if basepairs > 0:
+                return self.set_cds(min(cds_pos) + basepairs, max(cds_pos))
+            else:
+                return self.set_cds(min(cds_pos), max(cds_pos) + basepairs)
+        return None
+
+    def get_cds_bed(self):
+        cds_pos = [self.cdna_offset_of_pos(self.thickStart),
+                   self.cdna_offset_of_pos(self.thickEnd)]
+        return self.trim(min(cds_pos), max(cds_pos))
+
+    def get_cigar(self):
+        cigar = ''
+        r = range(self.blockCount)
+        xl = None
+        for x in r:
+            if xl is not None:
+                intronSize = abs(self.blockStarts[x] - self.blockSizes[xl]
+                                 - self.blockStarts[xl])
+                cigar += '%dN' % intronSize
+            cigar += '%dM' % self.blockSizes[x]
+            xl = x
+        return cigar
+
+    def get_cigar_md(self):
+        cigar = ''
+        md = ''
+        r = range(self.blockCount)
+        xl = None
+        for x in r:
+            if xl is not None:
+                intronSize = abs(self.blockStarts[x] - self.blockSizes[xl]
+                                 - self.blockStarts[xl])
+                cigar += '%dN' % intronSize
+            cigar += '%dM' % self.blockSizes[x]
+            xl = x
+        md = '%d' % sum(self.blockSizes)
+        return (cigar, md)
+
+    def get_translation(self, sequence=None):
+        translation = None
+        seq = sequence if sequence else self.get_spliced_seq()
+        if seq:
+            seqlen = len(seq) / 3 * 3
+            if seqlen >= 3:
+                translation = translate(seq[:seqlen])
+        return translation
+
+    def get_translations(self):
+        translations = []
+        seq = self.get_spliced_seq()
+        if seq:
+            for i in range(3):
+                translation = self.get_translation(sequence=seq[i:])
+                if translation:
+                    translations.append(translation)
+        return translations
+
+    def pos_of_cdna_offet(self, offset):
+        if offset is not None and 0 <= offset < sum(self.blockSizes):
+            r = list(range(self.blockCount))
+            rev = self.strand == '-'
+            if rev:
+                r.reverse()
+            nlen = 0
+            for x in r:
+                if offset < nlen + self.blockSizes[x]:
+                    if rev:
+                        return self.chromStart + self.blockStarts[x]\
+                               + self.blockSizes[x] - (offset - nlen)
+                    else:
+                        return self.chromStart + self.blockStarts[x]\
+                               + (offset - nlen)
+                nlen += self.blockSizes[x]
+        return None
+
+    def cdna_offset_of_pos(self, pos):
+        if not self.chromStart <= pos < self.chromEnd:
+            return -1
+        r = list(range(self.blockCount))
+        rev = self.strand == '-'
+        if rev:
+            r.reverse()
+        nlen = 0
+        for x in r:
+            bStart = self.chromStart + self.blockStarts[x]
+            bEnd = bStart + self.blockSizes[x]
+            if bStart <= pos < bEnd:
+                return nlen + (bEnd - pos if rev else pos - bStart)
+            nlen += self.blockSizes[x]
+
+    def apply_variant(self, pos, ref, alt):
+        pos = int(pos)
+        if not ref or not alt:
+            print("variant requires ref and alt sequences", file=sys.stderr)
+            return
+        if not self.chromStart <= pos <= self.chromEnd:
+            print("variant not in entry %s: %s %d < %d < %d" %
+                  (self.name, self.strand,
+                   self.chromStart, pos, self.chromEnd),
+                  file=sys.stderr)
+            print("%s" % str(self), file=sys.stderr)
+            return
+        if len(ref) != len(alt):
+            print("variant only works for snp: %s  %s" % (ref, alt),
+                  file=sys.stderr)
+            return
+        if not self.seq:
+            print("variant entry %s has no seq" % self.name, file=sys.stderr)
+            return
+        """
+        if self.strand  == '-':
+            ref = reverse_complement(ref)
+            alt = reverse_complement(alt)
+        """
+        bases = list(self.seq)
+        offset = pos - self.chromStart
+        for i in range(len(ref)):
+            # offset = self.cdna_offset_of_pos(pos+i)
+            if offset is not None:
+                bases[offset+i] = alt[i]
+            else:
+                print("variant offset %s: %s %d < %d < %d" %
+                      (self.name, self.strand, self.chromStart,
+                       pos+1, self.chromEnd), file=sys.stderr)
+                print("%s" % str(self), file=sys.stderr)
+        self.seq = ''.join(bases)
+        self.variants.append("g.%d%s>%s" % (pos+1, ref, alt))
+
+    def get_variant_bed(self, pos, ref, alt):
+        pos = int(pos)
+        if not ref or not alt:
+            print("variant requires ref and alt sequences", file=sys.stderr)
+            return None
+        if not self.chromStart <= pos <= self.chromEnd:
+            print("variant not in entry %s: %s %d < %d < %d" %
+                  (self.name, self.strand,
+                   self.chromStart, pos, self.chromEnd),
+                  file=sys.stderr)
+            print("%s" % str(self), file=sys.stderr)
+            return None
+        if not self.seq:
+            print("variant entry %s has no seq" % self.name, file=sys.stderr)
+            return None
+        tbed = BedEntry(chrom=self.chrom,
+                        chromStart=self.chromStart, chromEnd=self.chromEnd,
+                        name=self.name, score=self.score, strand=self.strand,
+                        thickStart=self.chromStart, thickEnd=self.chromEnd,
+                        itemRgb=self.itemRgb,
+                        blockCount=self.blockCount,
+                        blockSizes=self.blockSizes,
+                        blockStarts=self.blockStarts)
+        bases = list(self.seq)
+        offset = pos - self.chromStart
+        tbed.seq = ''.join(bases[:offset] + list(alt)
+                           + bases[offset+len(ref):])
+        if len(ref) != len(alt):
+            diff = len(alt) - len(ref)
+            rEnd = pos + len(ref)
+            # need to adjust blocks
+            #  change spans blocks,
+            for x in range(tbed.blockCount):
+                bStart = tbed.chromStart + tbed.blockStarts[x]
+                bEnd = bStart + tbed.blockSizes[x]
+                # change within a block or extends (last block)
+                #  adjust blocksize
+                #  seq:            GGGcatGGG
+                #  ref c alt tag:  GGGtagatGGG
+                #  ref cat alt a:  GGGaGGG
+                if bStart <= pos < rEnd < bEnd:
+                    tbed.blockSizes[x] += diff
+        return tbed
+
+    # (start, end)
+    def get_subrange(self, tstart, tstop, debug=False):
+        chromStart = self.chromStart
+        chromEnd = self.chromEnd
+        if debug:
+            print("%s" % (str(self)), file=sys.stderr)
+        r = list(range(self.blockCount))
+        if self.strand == '-':
+            r.reverse()
+        bStart = 0
+        bEnd = 0
+        for x in r:
+            bEnd = bStart + self.blockSizes[x]
+            if bStart <= tstart < bEnd:
+                if self.strand == '+':
+                    chromStart = self.chromStart + self.blockStarts[x] +\
+                        (tstart - bStart)
+                else:
+                    chromEnd = self.chromStart + self.blockStarts[x] +\
+                        self.blockSizes[x] - (tstart - bStart)
+            if bStart <= tstop < bEnd:
+                if self.strand == '+':
+                    chromEnd = self.chromStart + self.blockStarts[x] +\
+                        (tstop - bStart)
+                else:
+                    chromStart = self.chromStart + self.blockStarts[x] +\
+                        self.blockSizes[x] - (tstop - bStart)
+            if debug:
+                print("%3d %s\t%d\t%d\t%d\t%d\t%d\t%d" %
+                      (x, self.strand, bStart, bEnd,
+                       tstart, tstop, chromStart, chromEnd), file=sys.stderr)
+            bStart += self.blockSizes[x]
+        return(chromStart, chromEnd)
+
+    # get the blocks for sub range
+    def get_blocks(self, chromStart, chromEnd):
+        tblockCount = 0
+        tblockSizes = []
+        tblockStarts = []
+        for x in range(self.blockCount):
+            bStart = self.chromStart + self.blockStarts[x]
+            bEnd = bStart + self.blockSizes[x]
+            if bStart > chromEnd:
+                break
+            if bEnd < chromStart:
+                continue
+            cStart = max(chromStart, bStart)
+            tblockStarts.append(cStart - chromStart)
+            tblockSizes.append(min(chromEnd, bEnd) - cStart)
+            tblockCount += 1
+        return (tblockCount, tblockSizes, tblockStarts)
+
+    def trim(self, tstart, tstop, debug=False):
+        (tchromStart, tchromEnd) =\
+            self.get_subrange(tstart, tstop, debug=debug)
+        (tblockCount, tblockSizes, tblockStarts) =\
+            self.get_blocks(tchromStart, tchromEnd)
+        tbed = BedEntry(
+            chrom=self.chrom, chromStart=tchromStart, chromEnd=tchromEnd,
+            name=self.name, score=self.score, strand=self.strand,
+            thickStart=tchromStart, thickEnd=tchromEnd, itemRgb=self.itemRgb,
+            blockCount=tblockCount,
+            blockSizes=tblockSizes, blockStarts=tblockStarts)
+        if self.seq:
+            ts = tchromStart-self.chromStart
+            te = tchromEnd - tchromStart + ts
+            tbed.seq = self.seq[ts:te]
+        return tbed
+
+    def get_filtered_translations(self, untrimmed=False, filtering=True,
+                                  ignore_left_bp=0, ignore_right_bp=0,
+                                  debug=False):
+        translations = [None, None, None]
+        seq = self.get_spliced_seq()
+        ignore = (ignore_left_bp if self.strand == '+'
+                  else ignore_right_bp) / 3
+        block_sum = sum(self.blockSizes)
+        exon_sizes = [x for x in self.blockSizes]
+        if self.strand == '-':
+            exon_sizes.reverse()
+        splice_sites = [sum(exon_sizes[:x]) / 3
+                        for x in range(1, len(exon_sizes))]
+        if debug:
+            print("splice_sites: %s" % splice_sites, file=sys.stderr)
+        junc = splice_sites[0] if len(splice_sites) > 0 else exon_sizes[0]
+        if seq:
+            for i in range(3):
+                translation = self.get_translation(sequence=seq[i:])
+                if translation:
+                    tstart = 0
+                    tstop = len(translation)
+                    offset = (block_sum - i) % 3
+                    if debug:
+                        print("frame: %d\ttstart: %d  tstop: %d  " +
+                              "offset: %d\t%s" %
+                              (i, tstart, tstop, offset, translation),
+                              file=sys.stderr)
+                    if not untrimmed:
+                        tstart = translation.rfind('*', 0, junc) + 1
+                        stop = translation.find('*', junc)
+                        tstop = stop if stop >= 0 else len(translation)
+                    offset = (block_sum - i) % 3
+                    trimmed = translation[tstart:tstop]
+                    if debug:
+                        print("frame: %d\ttstart: %d  tstop: %d  " +
+                              "offset: %d\t%s" %
+                              (i, tstart, tstop, offset, trimmed),
+                              file=sys.stderr)
+                    if filtering and tstart > ignore:
+                        continue
+                    # get genomic locations for start and end
+                    if self.strand == '+':
+                        chromStart = self.chromStart + i + (tstart * 3)
+                        chromEnd = self.chromEnd - offset\
+                            - (len(translation) - tstop) * 3
+                    else:
+                        chromStart = self.chromStart + offset\
+                            + (len(translation) - tstop) * 3
+                        chromEnd = self.chromEnd - i - (tstart * 3)
+                    # get the blocks for this translation
+                    (tblockCount, tblockSizes, tblockStarts) =\
+                        self.get_blocks(chromStart, chromEnd)
+                    translations[i] = (chromStart, chromEnd, trimmed,
+                                       tblockCount, tblockSizes, tblockStarts)
+                    if debug:
+                        print("tblockCount: %d tblockStarts: %s " +
+                              "tblockSizes: %s" %
+                              (tblockCount, tblockStarts, tblockSizes),
+                              file=sys.stderr)
+        return translations
+
+    def get_seq_id(self, seqtype='unk:unk', reference='', frame=None):
+        # Ensembl fasta ID format
+        # >ID SEQTYPE:STATUS LOCATION GENE TRANSCRIPT
+        # >ENSP00000328693 pep:splice chromosome:NCBI35:1:904515:910768:1\
+        #   gene:ENSG00000158815:transcript:ENST00000328693\
+        #    gene_biotype:protein_coding transcript_biotype:protein_coding
+        frame_name = ''
+        chromStart = self.chromStart
+        chromEnd = self.chromEnd
+        strand = 1 if self.strand == '+' else -1
+        if frame is not None:
+            block_sum = sum(self.blockSizes)
+            offset = (block_sum - frame) % 3
+            frame_name = '_' + str(frame + 1)
+            if self.strand == '+':
+                chromStart += frame
+                chromEnd -= offset
+            else:
+                chromStart += offset
+                chromEnd -= frame
+        location = "chromosome:%s:%s:%s:%s:%s"\
+            % (reference, self.chrom, chromStart, chromEnd, strand)
+        seq_id = "%s%s %s %s" % (self.name, frame_name, seqtype, location)
+        return seq_id
+
+    def get_line(self, start_offset=0, end_offset=0):
+        if start_offset or end_offset:
+            s_offset = start_offset if start_offset else 0
+            e_offset = end_offset if end_offset else 0
+            if s_offset > self.chromStart:
+                s_offset = self.chromStart
+            chrStart = self.chromStart - s_offset
+            chrEnd = self.chromEnd + e_offset
+            blkSizes = self.blockSizes
+            blkSizes[0] += s_offset
+            blkSizes[-1] += e_offset
+            blkStarts = self.blockStarts
+            for i in range(1, self.blockCount):
+                blkStarts[i] += s_offset
+            items = [str(x) for x in [self.chrom, chrStart, chrEnd, self.name,
+                                      self.score, self.strand, self.thickStart,
+                                      self.thickEnd, self.itemRgb,
+                                      self.blockCount,
+                                      ','.join([str(x) for x in blkSizes]),
+                                      ','.join([str(x) for x in blkStarts])]]
+            return '\t'.join(items) + '\n'
+        return self.line