import sys
import os
import math
import re
import csv
import gzip
import itertools
import collections
try:
    import cStringIO
except:
    pass
import warnings
import numpy
cimport numpy

from HTSeq import StepVector
from HTSeq import _HTSeq_internal


###########################
# GenomicInterval
###########################

cdef str strand_plus = intern("+")
cdef str strand_minus = intern("-")
cdef str strand_nostrand = intern(".")

cdef class GenomicInterval:

    """A GenomicInterval specifies an interval (i.e., a range of 
    consecutive positions) on a reference genome.

    A GenomicInterval object has the following slots, some of which 
    are calculated from the other:

       chrom: The name of a sequence (i.e., chromosome, contig, or 
          the like). 
       start: The start of the interval. Even on the reverse strand,
          this is always the smaller of the two values 'start' and 'end'.
          Note that all positions should be given as 0-based value!
       end: The end of the interval. Following Python convention for 
          ranges, this in one more than the coordinate of the last base
          that is considered part of the sequence.
       strand: The strand, as a single character, '+' or '-'. '.' indicates
          that the strand is irrelavant. (Alternatively, pass a Strand object.)
       length: The length of the interval, i.e., end - start
       start_d: The "directional start" position. This is the position of the
         first base of the interval, taking the strand into account. Hence, 
         this is the same as 'start' except when strand == '-', in which 
         case it is end-1.
       end_d: The "directional end": Usually, the same as 'end', but for 
         strand=='-1', it is start-1.
    """

    def __init__(GenomicInterval self, str chrom, long start, long end,
                 str strand=strand_nostrand):
        """See the class docstring for the meaning of the slots. Note that 
        there is also a factory function, 'from_directional', to be used if
        you wish to specify start_d and length.
        """
        self.chrom = intern(chrom)
        self.start = start
        self.end = end
        self.strand = strand
        if self.start > self.end:
            raise ValueError, "start is larger than end"

    property strand:
        def __set__(self, strand):
            strand = intern(strand)
            if not(strand is strand_plus or strand is strand_minus or
                    strand is strand_nostrand):
                raise ValueError, "Strand must be'+', '-', or '.'."
            self._strand = strand

        def __get__(self):
            return self._strand

    def __reduce__(GenomicInterval self):
        return GenomicInterval, (self.chrom, self.start, self.end,
                                 self.strand)

    def __copy__(self):
        constr, args = self.__reduce__()
        return constr(*args)

    def __repr__(GenomicInterval self):
        return "<%s object '%s', [%d,%s), strand '%s'>" % \
            (self.__class__.__name__, self.chrom, self.start,
             str(self.end) if self.end != sys.maxsize else "Inf", self.strand)

    def __str__(GenomicInterval self):
        return "%s:[%d,%s)/%s" % \
            (self.chrom, self.start, str(self.end)
             if self.end != sys.maxsize else "Inf", self.strand)

    property length:

        """The length is calculated as end - start. If you set the length, 
        'start_d' will be preserved, i.e., 'end' is changed, unless the strand
        is '-', in which case 'start' is changed."""

        def __get__(GenomicInterval self):
            return self.end - self.start

        def __set__(GenomicInterval self, long newLength):
            if self._strand is not strand_minus:
                self.end = self.start + newLength
            else:
                self.start = self.end - newLength

    property start_d:
        """See the class docstring for the meaning of the 'directional start'.
        Note that if you set 'start_d', both the start and the end are changed, 
        such the interval gets the requested new directional start and its
        length stays unchanged."""

        def __get__(GenomicInterval self):
            if self._strand is not strand_minus:
                return self.start
            else:
                return self.end - 1

        def __set__(GenomicInterval self, long newStartd):
            if self._strand is not strand_minus:
                self.end = newStartd + self.length
                self.start = newStartd
            else:
                self.start = newStartd + 1 - self.length
                self.end = newStartd + 1

    property end_d:

        def __get__(GenomicInterval self):
            if self._strand is not strand_minus:
                return self.end
            else:
                return self.start - 1

    property start_as_pos:
        def __get__(GenomicInterval self):
            return GenomicPosition(self.chrom, self.start, self. strand)

    property end_as_pos:
        def __get__(GenomicInterval self):
            return GenomicPosition(self.chrom, self.end, self. strand)

    property start_d_as_pos:
        def __get__(GenomicInterval self):
            return GenomicPosition(self.chrom, self.start_d, self. strand)

    property end_d_as_pos:
        def __get__(GenomicInterval self):
            return GenomicPosition(self.chrom, self.end_d, self. strand)

    def __richcmp__(GenomicInterval self, GenomicInterval other, int op):
        if op == 2:  # ==
            if other == None:
                return False
            return self._strand is other._strand and \
                self.start == other.start and self.end == other.end
        elif op == 3:  # !=
            return not (self == other)
        else:
            raise NotImplementedError

    def __hash__(GenomicInterval self):
        return hash((self.chrom, self.start, self.end, self.strand))

    cpdef is_contained_in(GenomicInterval self, GenomicInterval iv):
        """Returns a boolean value indicating whether the 'self' interval 
        is fully within the 'iv' interval.

        This is deemed the case if
          - both are on the same chromosome, and    
          - both are on the same strand, or at least one of them is
             not stranded (i.e., has strand == '.'), and
          - self.start >= iv.start, and
          - self.end <= iv.end
        """
        if iv == None:
            return False
        if self.chrom != iv.chrom:
            return False
        if self._strand is not strand_nostrand and iv.strand is not strand_nostrand and \
                self.strand is not iv._strand:
            return False
        if self.start < iv.start or self.end > iv.end:
            return False
        return True

    cpdef contains(GenomicInterval self, GenomicInterval iv):
        """Returns a boolean value indicating whether the 'self' interval 
        fully contains the 'iv' interval.

        See 'is_contained_in' for the exact criteria.
        """
        if iv == None:
            return False
        return iv.is_contained_in(self)

    cpdef overlaps(GenomicInterval self, GenomicInterval iv):
        """Returns a boolean value indicating whether the 'self' interval 
        overlaps the 'iv' interval.

        This is deemed the case if
          - both are on the same chromosome, and    
          - both are on the same strand, or at least one of them is
             not stranded (i.e., has strand == '.'), and
          - the actual intervals overlap
        """
        if iv == None:
            return False
        if self.chrom != iv.chrom:
            return False
        if self.strand is not strand_nostrand and iv.strand is not strand_nostrand and \
                self.strand is not iv.strand:
            return False
        if self.start <= iv.start:
            return self.end > iv.start
        else:
            return iv.end > self.start

    def range(GenomicInterval self, long int step=1):
        """Generate an iterator over the GenomicPositions covered by the interval,
        running from start to end.
        """
        return _HTSeq_internal.GenomicInterval_range(self, step)

    def range_d(GenomicInterval self, long int step=1):
        """Generate an iterator over the GenomicPositions covered by the interval.
        running from start_d to end_d.
        """
        return _HTSeq_internal.GenomicInterval_ranged(self, step)

    cpdef extend_to_include(GenomicInterval self, GenomicInterval iv):
        """Extend the interval such that it includes iv."""
        if iv is None:
            raise TypeError, "Cannot extend an interval to include None."
        if self.chrom != iv.chrom:
            raise ValueError, "Cannot extend an interval to include an interval on another chromosome."
        if self.strand is not strand_nostrand and iv.strand is not strand_nostrand and \
                self.strand is not iv.strand:
            raise ValueError, "Cannot extend an interval to include an interval on another strand."
        self.start = min(self.start, iv.start)
        self.end = max(self.end, iv.end)

    def copy(self):
        return GenomicInterval(self.chrom, self.start, self.end, self.strand)


def GenomicInterval_from_directional(str chrom, long int start_d, long int length, str strand="."):
    strand = intern(strand)
    if strand.se is not strand_minus:
        return GenomicInterval(chrom, start_d, start_d + length, strand)
    else:
        return GenomicInterval(chrom, start_d - length + 1, start_d + 1, strand)


cdef class GenomicPosition(GenomicInterval):

    """A GenomicPosition specifies the position of a nucleotide or
    base pair on a reference genome.

    It has the following slots:
       chrom: The name of a sequence (i.e., chromosome, contig, or 
          the like). 
       pos: The position on the sequence specified by seqname.
          The position should always be given as 0-based value!
       strand: The strand, as a single character, '+' or '-'. '.' indicates
          that the strand is irrelavant.

    The GenomicPosition class is derived from GenomicInterval. Hence,
    a GenomicPosition is always a GenomicInterval of length 1. Do not tinker
    with the exposed GenomeInterval slots.
    """

    def __init__(self, str chrom, long int pos, str strand='.'):
        GenomicInterval.__init__(self, chrom, pos, pos + 1, strand)

    property pos:

        """As GenomicPosition is a subclass of GenomicInterval, 'pos' is actually
        just an alias for 'start_d'.
        """

        def __get__(self):
            return self.start_d

        def __set__(self, long newValue):
            self.start_d = newValue

    property end:

        def __get__(self):
            return self.start + 1

    property length:

        def __get__(self):
            return 1

    def __repr__(self):
        return "<%s object '%s':%d, strand '%s'>" % \
            (self.__class__.__name__, self.chrom, self.pos, self.strand)

    def __str__(self):
        return "%s:%d/%s" % (self.chrom, self.pos, self.strand)

    def __reduce__(GenomicPosition self):
        return GenomicPosition, (self.chrom, self.pos, self.strand)

    def copy(self):
        return GenomicPosition(self.chrom, self.pos, self.strand)


cdef class ChromVector(object):

    cdef public object array
    cdef public GenomicInterval iv
    cdef public int offset
    cdef public bint is_vector_of_sets
    cdef public str _storage

    @classmethod
    def create(cls, GenomicInterval iv, str typecode, str storage, str memmap_dir=""):
        ncv = cls()
        ncv.iv = iv
        if storage == "ndarray":
            if typecode != 'O':
                ncv.array = numpy.zeros(shape=(iv.length, ), dtype=typecode)
            else:
                ncv.array = numpy.empty(shape=(iv.length, ), dtype=typecode)
                ncv.array[:] = None
        elif storage == "memmap":
            ncv.array = numpy.memmap(shape=(iv.length, ), dtype=typecode,
                                     filename=os.path.join(memmap_dir, iv.chrom + iv.strand + ".nmm"), mode='w+')
        elif storage == "step":
            ncv.array = StepVector.StepVector.create(typecode=typecode)
        else:
            raise ValueError, "Illegal storage mode."
        ncv._storage = storage
        # TODO: Test whether offset works properly
        ncv.offset = iv.start
        ncv.is_vector_of_sets = False
        return ncv

    @classmethod
    def _create_view(cls, ChromVector vec, GenomicInterval iv):
        if iv.length == 0:
            raise IndexError, "Cannot subset to zero-length interval."
        v = cls()
        v.iv = iv
        v.array = vec.array
        v.offset = vec.offset
        v.is_vector_of_sets = vec.is_vector_of_sets
        v._storage = vec._storage
        return v

    def __getitem__(self, index):
        cdef slice index_slice
        cdef long int index_int
        cdef long int start, stop
        cdef GenomicInterval iv
        if isinstance(index, int):
            index_int = index
            if index_int < self.iv.start or index_int >= self.iv.end:
                raise IndexError
            return self.array[index_int - self.offset]
        elif isinstance(index, slice):
            index_slice = index
            if index_slice.start is not None:
                start = index_slice.start
                if start < self.iv.start:
                    raise IndexError, "start too small"
            else:
                start = self.iv.start
            if index_slice.stop is not None:
                stop = index_slice.stop
                if stop > self.iv.end:
                    raise IndexError, "stop too large"
            else:
                stop = self.iv.end
            iv = GenomicInterval(self.iv.chrom, start, stop, self.iv.strand)
            if not self.iv.contains(iv):
                raise IndexError
            return ChromVector._create_view(self, iv)
        elif isinstance(index, GenomicInterval):
            if not self.iv.contains(index):
                raise IndexError
            if self.iv.strand is strand_nostrand and \
                    index.strand is not strand_nostrand:
                iv = index.copy()   # Is this correct now?
                iv.strand = strand_nostrand
            return ChromVector._create_view(self, iv)
        else:
            raise TypeError, "Illegal index type"

    def __setitem__(self, index, value):
        cdef slice index_slice
        cdef long int start, stop
        if isinstance(value, ChromVector):
            if self.array is value.array and value.iv.start == index.start and \
                    value.iv.end == index.stop and (index.step is None or index.step == 1):
                return
            else:
                raise NotImplementedError, "Required assignment signature not yet implemented."
        if isinstance(index, int):
            self.array[index - self.iv.start] = value
        elif isinstance(index, slice):
            index_slice = index
            if index_slice.start is not None:
                start = index_slice.start
                if start < self.iv.start:
                    raise IndexError, "start too small"
            else:
                start = self.iv.start
            if index_slice.stop is not None:
                stop = index_slice.stop
                if stop > self.iv.end:
                    raise IndexError, "stop too large"
            else:
                stop = self.iv.end
            if start > stop:
                raise IndexError, "Start of interval is after its end."
            if start == stop:
                raise IndexError, "Cannot assign to zero-length interval."
            self.array[start - self.offset: stop -
                       self.iv.start: index.step] = value
        elif isinstance(index, GenomicInterval):
            if index.chrom != self.iv.chrom:
                raise KeyError, "Chromosome name mismatch."
            if self.iv.strand is not strand_nostrand and \
                    self.iv.strand is not self.index.strand:
                raise KeyError, "Strand mismatch."
            self.array[index.iv.start - self.iv.start,
                       index.iv.end - self.iv.start] = value
        else:
            raise TypeError, "Illegal index type"

    def __iadd__(self, value):
        if not self.is_vector_of_sets:
            self.array[self.iv.start - self.offset: self.iv.end -
                       self.offset].__iadd__(value)
        else:
            def addval(x):
                y = x.copy()
                y.add(value)
                return y
            self.apply(addval)
        return self

    def __iter__(self):
        return self.values()

    def values(self):
        return iter(self.array[self.iv.start - self.offset: self.iv.end - self.offset])

    def steps(self):
        return _HTSeq_internal.ChromVector_steps(self)

    def apply(self, fun):
        for iv, value in self.steps():
            self.array[iv.start - self.offset: iv.end -
                       self.offset] = fun(value)

    def __repr__(self):
        return "<%s object, %s, %s>" % (self.__class__.__name__, str(self.iv), self._storage)

    def __reduce__(self):
        assert self.__class__ is ChromVector
        return(_ChromVector_unpickle,
               (self.array, self.iv, self.offset, self.is_vector_of_sets, self._storage))


def _ChromVector_unpickle(array, iv, offset, is_vector_of_sets, _storage):
    cv = ChromVector()
    cv.array = array
    cv.iv = iv
    cv.offset = offset
    cv.is_vector_of_sets = is_vector_of_sets
    cv._storage = _storage
    return cv

cdef class GenomicArray(object):

    cdef public dict chrom_vectors
    cdef readonly bint stranded
    cdef readonly str typecode
    cdef public bint auto_add_chroms
    cdef readonly str storage
    cdef readonly str memmap_dir

    def __init__(self, object chroms, bint stranded=True, str typecode='d',
                 str storage='step', str memmap_dir=""):
        self.chrom_vectors = {}
        self.stranded = stranded
        self.typecode = typecode
        self.auto_add_chroms = chroms == "auto"
        if self.auto_add_chroms:
            chroms = []
            if storage != 'step':
                raise TypeError, "Automatic adding of chromosomes can " + \
                    " only be used with storage type 'StepVector'."
        elif isinstance(chroms, list):
            if storage != 'step':
                raise TypeError, "Indefinite-length chromosomes can " + \
                    " only be used with storage type 'StepVector'."
            chroms = dict([(c, sys.maxsize) for c in chroms])
        elif not isinstance(chroms, dict):
            raise TypeError, "'chroms' must be a list or a dict or 'auto'."
        self.storage = storage
        self.memmap_dir = memmap_dir

        for chrom in chroms:
            self.add_chrom(chrom, chroms[chrom])

    def __getitem__(self, index):
        if isinstance(index, GenomicInterval):
            if self.stranded and index.strand not in (strand_plus, strand_minus):
                raise KeyError, "Non-stranded index used for stranded GenomicArray."
            if self.auto_add_chroms and index.chrom not in self.chrom_vectors:
                self.add_chrom(index.chrom)
            if isinstance(index, GenomicPosition):
                if self.stranded:
                    return self.chrom_vectors[index.chrom][index.strand][index.pos]
                else:
                    return self.chrom_vectors[index.chrom][strand_nostrand][index.pos]
            else:
                if self.stranded:
                    return self.chrom_vectors[index.chrom][index.strand][index.start: index.end]
                else:
                    return self.chrom_vectors[index.chrom][strand_nostrand][index.start: index.end]
        else:
            return self.chrom_vectors[index]

    def __setitem__(self, index, value):
        cdef GenomicInterval index2
        if isinstance(value, ChromVector):
            if not isinstance(index, GenomicInterval):
                raise NotImplementedError, "Required assignment signature not yet implemented."
            index2 = index.copy()
            if not self.stranded:
                index2.strand = strand_nostrand
            if self.chrom_vectors[index2.chrom][index2.strand].array is value.array and index2 == value.iv:
                return
            raise NotImplementedError, "Required assignment signature not yet implemented."
        if isinstance(index, GenomicInterval):
            if self.stranded and index.strand not in (strand_plus, strand_minus):
                raise KeyError, "Non-stranded index used for stranded GenomicArray."
            if self.auto_add_chroms and index.chrom not in self.chrom_vectors:
                self.add_chrom(index.chrom)
            if self.stranded:
                self.chrom_vectors[index.chrom][index.strand][
                    index.start: index.end] = value
            else:
                self.chrom_vectors[index.chrom][strand_nostrand][
                    index.start: index.end] = value
        else:
            raise TypeError, "Illegal index type."

    def add_chrom(self, chrom, length=sys.maxsize, start_index=0):
        cdef GenomicInterval iv
        if length == sys.maxsize:
            iv = GenomicInterval(chrom, start_index, sys.maxsize, ".")
        else:
            iv = GenomicInterval(chrom, start_index, start_index + length, ".")
        if self.stranded:
            self.chrom_vectors[chrom] = {}
            iv.strand = "+"
            self.chrom_vectors[ chrom ][ strand_plus ] = \
                ChromVector.create(iv, self.typecode,
                                   self.storage, self.memmap_dir)
            iv = iv.copy()
            iv.strand = "-"
            self.chrom_vectors[ chrom ][ strand_minus ] = \
                ChromVector.create(iv, self.typecode,
                                   self.storage, self.memmap_dir)
        else:
            self.chrom_vectors[chrom] = {
                strand_nostrand:  ChromVector.create(iv, self.typecode,
                                                     self.storage,
                                                     self.memmap_dir)}

    def __reduce__(self):
        return (_GenomicArray_unpickle, (self.stranded, self.typecode, self.chrom_vectors))

    def write_bedgraph_file(self, file_or_filename, strand=".", track_options=""):
        if (not self.stranded) and strand != ".":
            raise ValueError, "Strand specified in unstranded GenomicArray."
        if self.stranded and strand not in (strand_plus, strand_minus):
            raise ValueError, "Strand must be specified for stranded GenomicArray."
        if hasattr(file_or_filename, "write"):
            f = file_or_filename
        else:
            f = open(file_or_filename, "w")
        if track_options == "":
            f.write("track type=bedGraph\n")
        else:
            f.write("track type=bedGraph %s\n" % track_options)
        for chrom in self.chrom_vectors:
            for iv, value in self.chrom_vectors[chrom][strand].steps():
                if iv.start == -sys.maxsize - 1 or iv.end == sys.maxsize:
                    continue
                f.write("%s\t%d\t%d\t%f\n" %
                        (iv.chrom, iv.start, iv.end, value))
        if not hasattr(file_or_filename, "write"):
            f.close()

    def steps(self):
        return _HTSeq_internal.GenomicArray_steps(self)


def _GenomicArray_unpickle(stranded, typecode, chrom_vectors):
    ga = GenomicArray({}, stranded, typecode)
    ga.chrom_vectors = chrom_vectors
    return ga


###########################
# Sequences
###########################


def _make_translation_table_for_complementation():
    return bytes.maketrans(b'ACGTacgt', b'TGCAtgca')

cdef bytes _translation_table_for_complementation = _make_translation_table_for_complementation()

cpdef bytes reverse_complement(bytes seq):
    """Returns the reverse complement of DNA sequence 'seq'. Does not yet
    work with extended IUPAC nucleotide letters or RNA."""

    return seq[::-1].translate(_translation_table_for_complementation)

base_to_column = {'A': 0, 'C': 1, 'G': 2, 'T': 3, 'N': 4}

cdef class Sequence(object):
    """A Sequence, typically of DNA, with a name.
    """

    def __init__(self, bytes seq, str name="unnamed"):
        self.seq = seq
        self.name = name
        self.descr = None

    cpdef Sequence get_reverse_complement(self, bint rename=True):
        if rename:
            return Sequence(
                reverse_complement(self.seq),
                "revcomp_of_" + self.name)
        else:
            return Sequence(
                reverse_complement(self.seq),
                self.name)

    def __str__(self):
        return self.seq.decode()

    def __repr__(self):
        return "<%s object '%s' (length %d)>" % (
            self.__class__.__name__, self.name, len(self.seq))

    def __len__(self):
        return len(self.seq)

    def __getitem__(self, item):
        if self.name.endswith("[part]"):
            new_name = self.name
        else:
            new_name = self.name + "[part]"
        return Sequence(self.seq[item], new_name)

    def __getstate__(self):
        return {'seq': self.seq,
                'name': self.name,
                'descr': self.descr}

    def __setstate__(self, state):
        self.seq = state['seq']
        self.name = state['name']
        self.descr = state['descr']

    def __reduce__(self):
        return (self.__class__, (self.seq, self.name), self.__getstate__())

    def write_to_fasta_file(self, fasta_file, characters_per_line=70):
        """Write sequence to file in FASTA format.

        Arguments:
                - fasta_file (file handle): destination file
                    - characters_per_line (int >=0): if 0, write the whole sequence on a single line. Otherwise, break into several lines if the sequence is long enough.

        """
        if self.descr is not None:
            fasta_file.write(">%s %s\n" % (self.name, self.descr))
        else:
            fasta_file.write(">%s\n" % self.name)

        if characters_per_line == 0:
            fasta_file.write(self.seq.decode() + "\n")
        else:
            i = 0
            while i * characters_per_line < len(self.seq):
                fasta_file.write(
                    self.seq[i * characters_per_line: (i + 1) * characters_per_line].decode() + "\n")
                i += 1

    cpdef object add_bases_to_count_array(Sequence self, numpy.ndarray count_array_):

        cdef numpy.ndarray[numpy.int_t, ndim = 2] count_array = count_array_
        cdef int seq_length = len(self.seq)

        if numpy.PyArray_DIMS(count_array)[0] < seq_length:
            raise ValueError, "'count_array' too small for sequence."
        if numpy.PyArray_DIMS(count_array)[1] < 5:
            raise ValueError, "'count_array' has too few columns."

        cdef numpy.npy_intp i
        cdef char b
        cdef char * seq_cstr = self.seq
        for i in range(seq_length):
            b = seq_cstr[i]
            if b in [b'A', b'a']:
                count_array[i, 0] += 1
            elif b in [b'C', b'c']:
                count_array[i, 1] += 1
            elif b in [b'G', b'g']:
                count_array[i, 2] += 1
            elif b in [b'T', b't']:
                count_array[i, 3] += 1
            elif b in [b'N', b'n', b'.']:
                count_array[i, 4] += 1
            else:
                raise ValueError, "Illegal base letter encountered."

        return None

    cpdef Sequence trim_left_end(Sequence self, Sequence pattern, float mismatch_prop=0.):
        cdef int seqlen = len(self.seq)
        cdef int patlen = len(pattern.seq)
        cdef int minlen
        if seqlen < patlen:
            minlen = seqlen
        else:
            minlen = patlen
        cdef char * seq_cstr = self.seq
        cdef char * pat_cstr = pattern.seq
        cdef int match = 0
        cdef int i, j
        cdef int num_mismatches
        for i in range(1, minlen + 1):
            num_mismatches = 0
            for j in range(i):
                if seq_cstr[j] != pat_cstr[patlen - i + j]:
                    num_mismatches += 1
                    if num_mismatches > mismatch_prop * i:
                        break
            else:
                match = i
        return self[match: seqlen]

    cpdef Sequence trim_right_end(Sequence self, Sequence pattern, float mismatch_prop=0.):
        cdef int seqlen = len(self.seq)
        cdef int patlen = len(pattern.seq)
        cdef int minlen
        if seqlen < patlen:
            minlen = seqlen
        else:
            minlen = patlen
        cdef char * seq_cstr = self.seq
        cdef char * pat_cstr = pattern.seq
        cdef int match = 0
        cdef int i, j
        cdef int num_mismatches
        for i in range(1, minlen + 1):
            num_mismatches = 0
            for j in range(i):
                if seq_cstr[seqlen - i + j] != pat_cstr[j]:
                    num_mismatches += 1
                    if num_mismatches > mismatch_prop * i:
                        break
            else:
                match = i
        return self[0: seqlen - match]


cdef class SequenceWithQualities(Sequence):
    """A Sequence with base-call quality scores.
    It now has property  'qual', an integer NumPy array of Sanger/Phred 
    quality scores of the  base calls.
    """

    def __init__(self, bytes seq, str name, bytes qualstr, str qualscale="phred"):
        """ Construct a SequenceWithQuality object.

          seq       - The actual sequence.
          name      - The sequence name or ID
          qualstr   - The quality string. Must have the same length as seq
          qualscale - The encoding scale of the quality string. Must be one of
                        "phred", "solexa", "solexa-old", or "noquals" )
        """
        Sequence.__init__(self, seq, name)
        if qualscale != "noquals":
            if len(seq) != len(qualstr):
                raise ValueError, "'seq' and 'qualstr' do not have the same length."
            self._qualstr = qualstr
        else:
            self._qualstr = b''
        self._qualscale = qualscale
        self._qualarr = None
        self._qualstr_phred = b''

    cdef _fill_qual_arr(SequenceWithQualities self):
        cdef int seq_len = len(self.seq)
        if self._qualscale == "missing":
            raise ValueError, "Quality string missing."
        if seq_len != len(self._qualstr):
            raise ValueError, "Quality string has not the same length as sequence."
        cdef numpy.ndarray[numpy.uint8_t, ndim= 1] qualarr = numpy.empty((seq_len, ), numpy.uint8)
        cdef int i
        cdef char * qualstr = self._qualstr
        if self._qualscale == "phred":
            for i in range(seq_len):
                qualarr[i] = qualstr[i] - 33
        elif self._qualscale == "solexa":
            for i in range(seq_len):
                qualarr[i] = qualstr[i] - 64
        elif self._qualscale == "solexa-old":
            for i in range(seq_len):
                qualarr[i] = 10 * \
                    math.log10(1 + 10 ** (qualstr[i] - 64) / 10.0)
        else:
            raise ValueError, "Illegal quality scale '%s'." % self._qualscale
        self._qualarr = qualarr

    property qual:
        def __get__(self):
            if self._qualarr is None:
                self._fill_qual_arr()
            return self._qualarr

        def __set__(self, newvalue):
            if not (isinstance(newvalue, numpy.ndarray) and newvalue.dtype == numpy.uint8):
                raise TypeError, "qual can only be assigned a numpy array of type numpy.uint8"
            if not (newvalue.shape == (len(self.seq), )):
                raise TypeError, "assignment to qual with illegal shape"
            self._qualarr = newvalue
            self._qualstr = b""
            self._qualscale = "none"
            self._qualstr_phred = b""
            # Experimentally trying to set qualstr when the array is modified
            # directly
            tmp = self.qualstr
            self._qualstr = self._qualstr_phred

    def __repr__(self):
        return "<%s object '%s'>" % (self.__class__.__name__, self.name)

    def __getitem__(self, item):
        if self.name.endswith("[part]"):
            new_name = self.name
        else:
            new_name = self.name + "[part]"
        return SequenceWithQualities(
            self.seq[item], new_name, self.qualstr[item])

    @property
    def qualstr(self):
        cdef int seqlen
        cdef char * qualstr_phred_cstr = self._qualstr_phred
        cdef int i
        cdef numpy.ndarray[numpy.uint8_t, ndim = 1] qual_array
        if qualstr_phred_cstr[0] == 0:
            if self._qualscale == "noquals":
                raise ValueError, "Quality string missing"
            if self._qualscale == "phred":
                self._qualstr_phred = self._qualstr
            else:
                seqlen = len(self.seq)
                # FIXME: is this fixed now?
                self._qualstr_phred = b' ' * seqlen
                qualstr_phred_cstr = self._qualstr_phred
                if self._qualarr is None:
                    self._fill_qual_arr()
                qual_array = self._qualarr
                for i in range(seqlen):
                    qualstr_phred_cstr[i] = 33 + qual_array[i]
        return self._qualstr_phred

    def write_to_fastq_file(self, fastq_file):
        if hasattr(self, "descr") and self.descr is not None:
            fastq_file.write("@%s %s\n" % (self.name, self.descr))
        else:
            fastq_file.write("@%s\n" % self.name)
        fastq_file.write(self.seq.decode() + "\n")
        fastq_file.write("+\n")
        fastq_file.write(self.qualstr.decode() + "\n")

    def get_fastq_str(self, bint convert_to_phred=False):
        sio = cStringIO.StringIO()
        self.write_to_fastq_file(sio, convert_to_phred)
        return sio.getvalue()

    cpdef SequenceWithQualities get_reverse_complement(self, bint rename=True):
        cdef SequenceWithQualities res
        if rename:
            res = SequenceWithQualities(
                reverse_complement(self.seq),
                "revcomp_of_" + self.name,
                self._qualstr[::-1],
                self._qualscale)
        else:
            res = SequenceWithQualities(
                reverse_complement(self.seq),
                self.name,
                self._qualstr[::-1],
                self._qualscale)
        if self._qualarr is not None:
            res._qualarr = self._qualarr[::-1]
        return res

    cpdef object add_qual_to_count_array(SequenceWithQualities self,
                                         numpy.ndarray count_array_):

        cdef numpy.ndarray[numpy.int_t, ndim = 2] count_array = count_array_
        if self._qualarr is None:
            self._fill_qual_arr()
        cdef numpy.ndarray[numpy.uint8_t, ndim = 1] qual_array = self._qualarr

        cdef numpy.npy_intp seq_length = numpy.PyArray_DIMS(qual_array)[0]
        cdef numpy.npy_intp qual_size = numpy.PyArray_DIMS(count_array)[1]

        if seq_length > numpy.PyArray_DIMS(count_array)[0]:
            raise ValueError, "'count_array' too small for sequence."

        cdef numpy.npy_intp i
        cdef numpy.npy_int q
        for i in range(seq_length):
            q = qual_array[i]
            if(q >= qual_size):
                raise ValueError, "Too large quality value encountered."
            count_array[i, q] += 1

        return None

    cpdef SequenceWithQualities trim_left_end_with_quals(SequenceWithQualities self,
                                                         Sequence pattern, int max_mm_qual=5):
        cdef int seqlen = len(self.seq)
        cdef int patlen = len(pattern.seq)
        cdef int minlen
        if seqlen < patlen:
            minlen = seqlen
        else:
            minlen = patlen
        cdef char * seq_cstr = self.seq
        cdef char * pat_cstr = pattern.seq
        cdef int match = 0
        cdef int i, j
        cdef int sum_mm_qual
        if self._qualarr is None:
            self._fill_qual_arr()
        cdef numpy.ndarray[numpy.uint8_t, ndim = 1] qual_array = self._qualarr
        for i in range(1, minlen + 1):
            num_mismatches = 0
            for j in range(i):
                if seq_cstr[j] != pat_cstr[patlen - i + j]:
                    sum_mm_qual += qual_array[j]
                    if sum_mm_qual > max_mm_qual:
                        break
            else:
                match = i
        return self[match: seqlen]

    cpdef SequenceWithQualities trim_right_end_with_quals(SequenceWithQualities self,
                                                          Sequence pattern, int max_mm_qual=5):
        cdef int seqlen = len(self.seq)
        cdef int patlen = len(pattern.seq)
        cdef int minlen
        if seqlen < patlen:
            minlen = seqlen
        else:
            minlen = patlen
        cdef char * seq_cstr = self.seq
        cdef char * pat_cstr = pattern.seq
        cdef int match = 0
        cdef int i, j
        cdef int sum_mm_qual
        if self._qualarr is None:
            self._fill_qual_arr()
        cdef numpy.ndarray[numpy.uint8_t, ndim = 1] qual_array = self._qualarr
        for i in range(1, minlen + 1):
            sum_mm_qual = 0
            for j in range(i):
                if seq_cstr[seqlen - i + j] != pat_cstr[j]:
                    sum_mm_qual += qual_array[seqlen - i + j]
                    if sum_mm_qual > max_mm_qual:
                        break
            else:
                match = i
        return self[0: seqlen - match]


###########################
# Alignment
###########################

cdef class Alignment(object):

    """Alignment base type:

    An alignment object can be defined in different ways but will always
    provide these attributes:
      read:      a SequenceWithQualities object with the read
      aligned:   whether the read is aligned
      iv:        a GenomicInterval object with the alignment position 
    """

    def __init__(self, read, iv):
        self._read = read
        self.iv = iv

    @property
    def read(self):
        return self._read

    def __repr__(self):
        cdef str s
        if self.paired_end:
            s = "Paired-end read"
        else:
            s = "Read"
        if self.aligned:
            return "<%s object: %s '%s' aligned to %s>" % (
                self.__class__.__name__, s, self.read.name, str(self.iv))
        else:
            return "<%s object: %s '%s', not aligned>" % (
                self.__class__.__name__, s, self.read.name)

    @property
    def paired_end(self):
        return False

    @property
    def aligned(self):
        """Returns True unless self.iv is None. The latter indicates that
        this record decribes a read for which no alignment was found.
        """
        return self.iv is not None

cdef class AlignmentWithSequenceReversal(Alignment):

    """Many aligners report the read's sequence in reverse-complemented form
    when it was mapped to the reverse strand. For such alignments, a 
    daughter class of this one should be used.

    Then, the read is stored as aligned in the 'read_as_aligned' field,
    and get reverse-complemented back to the sequenced form when the 'read'
    attribute is sequenced.
    """

    def __init__(self, SequenceWithQualities read_as_aligned, GenomicInterval iv):
        self.read_as_aligned = read_as_aligned
        self._read_as_sequenced = None
        self.iv = iv

    property read:
        def __get__(self):
            if self._read_as_sequenced is None:
                if (not self.aligned) or self.iv.strand != "-":
                    self._read_as_sequenced = self.read_as_aligned
                else:
                    self._read_as_sequenced = self.read_as_aligned.get_reverse_complement()
                    self._read_as_sequenced.name = self.read_as_aligned.name
            return self._read_as_sequenced
        # def __set__( self, read ):
        #   self.read_as_aligned = read
        #   self._read_as_sequenced = None


cdef class BowtieAlignment(AlignmentWithSequenceReversal):

    """When reading in a Bowtie file, objects of the class BowtieAlignment
    are returned. In addition to the 'read' and 'iv' fields (see Alignment
    class), the fields 'reserved' and 'substitutions' are provided. These 
    contain the content of the respective columns of the Bowtie output 

    [A parser for the substitutions field will be added soon.]
    """

    cdef public str reserved
    cdef public str substitutions

    def __init__(self, bowtie_line):
        cdef str readId, strand, chrom, position, read, qual
        cdef int positionint
        (readId, strand, chrom, position, read, qual,
         self.reserved, self.substitutions) = bowtie_line.split('\t')
        positionint = int(position)
        AlignmentWithSequenceReversal.__init__(self,
                                               SequenceWithQualities(
                                                   read, readId, qual),
                                               GenomicInterval(chrom, positionint, positionint + len(read), strand))


cigar_operation_names = {
    'M': 'matched',
    'I': 'inserted',
    'D': 'deleted',
    'N': 'skipped',
    'S': 'soft-clipped',
    'H': 'hard-clipped',
    'P': 'padded',
    '=': 'sequence-matched',
    'X': 'sequence-mismatched'}

cdef class CigarOperation(object):

    cdef public str type
    cdef public int size
    cdef public GenomicInterval ref_iv
    cdef public int query_from, query_to

    def __init__(self, str type_, int size, int rfrom, int rto, int qfrom,
                 int qto, str chrom, str strand, bint check=True):
        self.type = type_
        self.size = size
        self.ref_iv = GenomicInterval(chrom, rfrom, rto, strand)
        self.query_from = qfrom
        self.query_to = qto
        if check and not self.check():
            raise ValueError, "Inconsistent CIGAR operation."

    def __repr__(self):
        return "< %s: %d base(s) %s on ref iv %s, query iv [%d,%d) >" % (
            self.__class__.__name__, self.size, cigar_operation_names[
                self.type],
            str(self.ref_iv), self.query_from, self.query_to)

    def check(CigarOperation self):
        cdef int qlen = self.query_to - self.query_from
        cdef int rlen = self.ref_iv.length
        if self.type == 'M' or self.type == '=' or self.type == 'X':
            if not (qlen == self.size and rlen == self.size):
                return False
        elif self.type == 'I' or self.type == 'S':
            if not (qlen == self.size and rlen == 0):
                return False
        elif self.type == 'D' or self.type == 'N':
            if not (qlen == 0 and rlen == self.size):
                return False
        elif self.type == 'H' or self.type == 'P':
            if not (qlen == 0 and rlen == 0):
                return False
        else:
            return False
        return True

_re_cigar_codes = re.compile('([MIDNSHP=X])')

cpdef list parse_cigar(str cigar_string, int ref_left=0, str chrom="", str strand="."):
    cdef list split_cigar, cl
    cdef int size
    cdef str code
    split_cigar = _re_cigar_codes.split(cigar_string)
    if split_cigar[-1] != '' or len(split_cigar) % 2 != 1:
        raise ValueError, "Illegal CIGAR string '%s'" % cigar_string
    cl = []
    for i in range(len(split_cigar) // 2):
        try:
            size = int(split_cigar[2 * i])
        except ValueError:
            raise ValueError, "Illegal CIGAR string '%s'" % cigar_string
        code = split_cigar[2 * i + 1]
        cl.append((code, size))
    return build_cigar_list(cl, ref_left, chrom, strand)

cpdef list build_cigar_list(list cigar_pairs, int ref_left=0, str chrom="", str strand="."):
    cdef list split_cigar, res
    cdef int rpos, qpos, size
    cdef str code
    rpos = ref_left
    qpos = 0
    res = []
    for code, size in cigar_pairs:
        if code == 'M' or code == '=' or code == 'X':
            res.append(CigarOperation(
                code, size, rpos, rpos + size, qpos, qpos + size, chrom, strand))
            rpos += size
            qpos += size
        elif code == 'I':
            res.append(CigarOperation(
                'I', size, rpos, rpos, qpos, qpos + size, chrom, strand))
            qpos += size
        elif code == 'D':
            res.append(CigarOperation(
                'D', size, rpos, rpos + size, qpos, qpos, chrom, strand))
            rpos += size
        elif code == 'N':
            res.append(CigarOperation(
                'N', size, rpos, rpos + size, qpos, qpos, chrom, strand))
            rpos += size
        elif code == 'S':
            res.append(CigarOperation(
                'S', size, rpos, rpos, qpos, qpos + size, chrom, strand))
            qpos += size
        elif code == 'H':
            res.append(CigarOperation(
                'H', size, rpos, rpos, qpos, qpos, chrom, strand))
        elif code == 'P':
            res.append(CigarOperation(
                'P', size, rpos, rpos, qpos, qpos, chrom, strand))
        else:
            raise ValueError, "Unknown CIGAR code '%s' encountered." % code
    return res

cdef _parse_SAM_optional_field_value(str field):
    if len(field) < 5 or field[2] != ':' or field[4] != ':':
        raise ValueError, "Malformatted SAM optional field '%'" % field
    if field[3] == 'A':
        return field[5]
    elif field[3] == 'i':
        return int(field[5:])
    elif field[3] == 'f':
        return float(field[5:])
    elif field[3] == 'Z':
        return field[5:]
    elif field[3] == 'H':
        return int(field[5:], 16)
    elif field[3] == 'B':
        if field[5] == 'f':
            return numpy.array(field[7:].split(','), float)
        else:
            return numpy.array(field[7:].split(','), int)
    else:
        raise ValueError, "SAM optional field with illegal type letter '%s'" % field[2]

cigar_operation_codes = ['M', 'I', 'D', 'N', 'S', 'H', 'P', '=', 'X']
cigar_operation_code_dict = dict(
    [(x, i) for i, x in enumerate(cigar_operation_codes)])

cdef class SAM_Alignment(AlignmentWithSequenceReversal):

    """When reading in a SAM file, objects of the class SAM_Alignment
    are returned. In addition to the 'read', 'iv' and 'aligned' fields (see 
    Alignment class), the following fields are provided:
     - aQual: the alignment quality score
     - cigar: a list of CigarOperatio objects, describing the alignment
     - tags: the extra information tags [not yet implemented]
    """

    def to_pysam_AlignedSegment(self, sf):
        try:
            import pysam
        except ImportError:
            sys.stderr.write(
                "Please Install PySam to use this functionality (http://code.google.com/p/pysam/)")
            raise

        a = pysam.AlignedSegment()
        a.query_sequence = self.read.seq if self.iv == None or self.iv.strand == '+' else self.read.get_reverse_complement().seq
        a.query_qualities = self.read.qual if self.iv == None or self.iv.strand == '+' else self.read.get_reverse_complement().qual
        a.query_name = self.read.name
        a.flag = self.flag
        a.tags = self.optional_fields
        if self.aligned:
            a.cigartuples = [(cigar_operation_code_dict[c.type], c.size)
                             for c in self.cigar]
            a.reference_start = self.iv.start
            a.reference_id = sf.gettid(self.iv.chrom)
            a.template_length = self.inferred_insert_size
            a.mapping_quality = self.aQual
        else:
            a.reference_start = -1
            a.reference_id = -1
        if self.mate_aligned:
            a.next_reference_id = sf.gettid(self.mate_start.chrom)
            a.next_reference_start = self.mate_start.start
        else:
            a.next_reference_id = -1
            a.next_reference_start = -1
        return a

    def to_pysam_AlignedRead(self, sf):
        try:
            import pysam
        except ImportError:
            sys.stderr.write(
                "Please Install PySam to use this functionality (http://code.google.com/p/pysam/)")
            raise

        a = pysam.AlignedRead()
        a.seq = self.read.seq
        a.qual = self.read.qualstr
        a.qname = self.read.name
        a.flag = self.flag
        a.tags = self.optional_fields
        if self.aligned:
            a.cigar = [(cigar_operation_code_dict[c.type], c.size)
                       for c in self.cigar]
            a.pos = self.iv.start
            a.tid = sf.gettid(self.iv.chrom)
            a.isize = self.inferred_insert_size
            a.mapq = self.aQual
        else:
            a.pos = -1
            a.tid = -1
        if self.mate_aligned:
            a.mrnm = sf.gettid(self.mate_start.chrom)
            a.mpos = self.mate_start.start
        else:
            a.mrnm = -1
            a.mpos = -1
        return a

    @classmethod
    def from_pysam_AlignedRead(cls, read, samfile):
        strand = "-" if read.is_reverse else "+"
        if not read.is_unmapped:
            chrom = samfile.getrname(read.tid)
            iv = GenomicInterval(chrom, read.pos, read.aend, strand)
        else:
            iv = None
        if read.qual != b"*":
            seq = SequenceWithQualities(
                read.query_sequence.encode(), read.qname, read.qual.encode())
        else:
            seq = SequenceWithQualities(read.query_sequence.encode(
            ), read.qname, read.qual.encode(), "noquals")
        a = SAM_Alignment(seq, iv)
        a.cigar = build_cigar_list([(cigar_operation_codes[code], length) for (
            code, length) in read.cigar], read.pos, chrom, strand) if iv != None else []
        a.inferred_insert_size = read.isize
        a.aQual = read.mapq
        a.flag = read.flag
        a.proper_pair = read.is_proper_pair
        a.not_primary_alignment = read.is_secondary
        a.failed_platform_qc = read.is_qcfail
        a.pcr_or_optical_duplicate = read.is_duplicate
        a.supplementary = read.is_supplementary
        a.original_sam_line = ""
        a.optional_fields = read.tags
        if read.is_paired:
            # These two should be but are not always consistent
            if (not read.mate_is_unmapped) and (read.mrnm != -1):
                strand = "-" if read.mate_is_reverse else "+"
                a.mate_start = GenomicPosition(
                    samfile.getrname(read.mrnm), read.mpos, strand)
            else:
                a.mate_start = None
            if read.is_read1:
                a.pe_which = intern("first")
            elif read.is_read2:
                a.pe_which = intern("second")
            else:
                a.pe_which = intern("unknown")
        else:
            a.pe_which = intern("not_paired_end")
        return a

    @classmethod
    def from_pysam_AlignedSegment(cls, read, samfile):
        strand = "-" if read.is_reverse else "+"
        if not read.is_unmapped:
            chrom = samfile.getrname(read.tid)
            iv = GenomicInterval(chrom, read.reference_start,
                                 read.reference_end, strand)
        else:
            iv = None
        seq = SequenceWithQualities(
            read.query_sequence.encode(), read.query_name, b'', 'noquals')
        if read.query_qualities != None:
            seq.qual = numpy.array(read.query_qualities)
        a = SAM_Alignment(seq, iv)
        a.cigar = build_cigar_list([(cigar_operation_codes[code], length) for (
            code, length) in read.cigartuples], read.reference_start, chrom, strand) if iv != None else []
        a.inferred_insert_size = read.template_length
        a.aQual = read.mapping_quality
        a.flag = read.flag
        a.proper_pair = read.is_proper_pair
        a.not_primary_alignment = read.is_secondary
        a.failed_platform_qc = read.is_qcfail
        a.pcr_or_optical_duplicate = read.is_duplicate
        a.supplementary = read.is_supplementary
        a.original_sam_line = ""
        a.optional_fields = read.tags
        if read.is_paired:
            # These two should be but are not always consistent
            if (not read.mate_is_unmapped) and (read.mrnm != -1):
                strand = "-" if read.mate_is_reverse else "+"
                a.mate_start = GenomicPosition(samfile.getrname(
                    read.mrnm), read.next_reference_start, strand)
            else:
                a.mate_start = None
            if read.is_read1:
                a.pe_which = intern("first")
            elif read.is_read2:
                a.pe_which = intern("second")
            else:
                a.pe_which = intern("unknown")
        else:
            a.pe_which = intern("not_paired_end")
        return a

    @classmethod
    def from_SAM_line(cls, line):
        cdef str qname, flag, rname, pos, mapq, cigar,
        cdef str mrnm, mpos, isize, seq, qual
        cdef list optional_fields
        cdef int posint, flagint
        cdef str strand
        cdef list cigarlist
        cdef SequenceWithQualities swq

        fields = line.rstrip().split("\t")
        if len(fields) < 10:
            raise ValueError, "SAM line does not contain at least 11 tab-delimited fields."
        (qname, flag, rname, pos, mapq, cigar, mrnm, mpos, isize,
         seq, qual) = fields[0:11]
        optional_fields = fields[11:]

        if seq.count("=") > 0:
            raise ValueError, "Sequence in SAM file contains '=', which is not supported."
        if seq.count(".") > 0:
            raise ValueError, "Sequence in SAM file contains '.', which is not supported."
        flagint = int(flag)

        if flagint & 0x0004:     # flag "query sequence is unmapped"
            iv = None
            cigarlist = None
        else:
            if rname == "*":
                raise ValueError, "Malformed SAM line: RNAME == '*' although flag bit &0x0004 cleared"
            # SAM is one-based, but HTSeq is zero-based!
            posint = int(pos) - 1
            if flagint & 0x0010:      # flag "strand of the query"
                strand = "-"
            else:
                strand = "+"
            cigarlist = parse_cigar(cigar, posint, rname, strand)
            iv = GenomicInterval(
                rname, posint, cigarlist[-1].ref_iv.end, strand)

        if qual != "*":
            swq = SequenceWithQualities(
                seq.upper().encode(), qname, qual.upper().encode())
        else:
            swq = SequenceWithQualities(
                seq.upper().encode(), qname, b"", "noquals")

        alnmt = SAM_Alignment(swq, iv)
        alnmt.flag = flagint
        alnmt.cigar = cigarlist
        alnmt.optional_fields = [
            (field[:2], _parse_SAM_optional_field_value(field)) for field in optional_fields]
        alnmt.aQual = int(mapq)
        alnmt.inferred_insert_size = int(isize)
        alnmt.original_sam_line = line

        if flagint & 0x0001:         # flag "read is paired in sequencing"
            if flagint & 0x0008:      # flag "mate is unmapped"
                alnmt.mate_start = None
            else:
                if mrnm == "*":
                    raise ValueError, "Malformed SAM line: MRNM == '*' although flag bit &0x0008 cleared"
                posint = int(mpos) - 1
                if flagint & 0x0020:   # flag "strand of the mate"
                    strand = "-"
                else:
                    strand = "+"
                alnmt.mate_start = GenomicPosition(mrnm, posint, strand)
                if alnmt.mate_start.chrom == "=":
                    if alnmt.iv is not None:
                        alnmt.mate_start.chrom = alnmt.iv.chrom
            if flagint & 0x0040:
                alnmt.pe_which = intern("first")
            elif flagint & 0x0080:
                alnmt.pe_which = intern("second")
            else:
                alnmt.pe_which = intern("unknown")
        else:
            alnmt.mate_start = None
            alnmt.pe_which = intern("not_paired_end")

        alnmt.proper_pair = flagint & 0x0002 > 0
        alnmt.not_primary_alignment = flagint & 0x0100 > 0
        alnmt.failed_platform_qc = flagint & 0x0200 > 0
        alnmt.pcr_or_optical_duplicate = flagint & 0x0400 > 0
        alnmt.supplementary = flagint & 0x0800 > 0

        return alnmt

    property flag:
        def __get__(self):
            return self._flag

        def __set__(self, value):
            self._flag = value

    @property
    def paired_end(self):
        return self.pe_which != "not_paired_end"

    @property
    def mate_aligned(self):
        return self.mate_start is not None

    def get_sam_line(self):
        cdef str cigar = ""
        cdef GenomicInterval query_start, mate_start
        cdef CigarOperation cop

        if self.aligned:
            query_start = self.iv
        else:
            query_start = GenomicPosition("*", -1)

        if self.mate_start is not None:
            mate_start = self.mate_start
        else:
            mate_start = GenomicPosition("*", -1)

        if self.cigar is not None:
            for cop in self.cigar:
                cigar += str(cop.size) + cop.type
        else:
            cigar = "*"

        return '\t'.join(
                (self.read.name,
                 str(self.flag),
                 query_start.chrom,
                 str(query_start.start + 1),
                 str(self.aQual),
                 cigar,
                 mate_start.chrom,
                 str(mate_start.pos + 1),
                 str(self.inferred_insert_size),
                 self.read_as_aligned.seq.decode(),
                 self.read_as_aligned.qualstr.decode(),
                 '\t'.join(self.raw_optional_fields())))

    def optional_field(SAM_Alignment self, str tag):
        res = [p for p in self.optional_fields if p[0] == tag]
        if len(res) == 1:
            return res[0][1]
        else:
            if len(res) == 0:
                raise KeyError, "SAM optional field tag %s not found" % tag
            else:
                raise ValueError, "SAM optional field tag %s not unique" % tag

    def raw_optional_fields(self):
        res = []
        for op in self.optional_fields:
            if op[1].__class__ == str:
                if len(op[1]) == 1:
                    tc = "A"
                else:
                    tc = "Z"
            elif op[1].__class__ == int:
                tc = "i"
            elif op[1].__class__ == float:
                tc = "j"
            else:
                tc = "H"
            res.append(":".join([op[0], tc, str(op[1])]))
        return res


###########################
# Helpers
###########################

cpdef list quotesafe_split(bytes s, bytes split=b';', bytes quote=b'"'):
    cdef list l = []
    cdef int i = 0
    cdef int begin_token = 0
    cdef bint in_quote = False
    cdef char * s_c = s
    cdef char split_c = split[0]
    cdef char quote_c = quote[0]
    if len(split) != 1:
        raise ValueError, "'split' must be length 1"
    if len(quote) != 1:
        raise ValueError, "'quote' must be length 1"
    while s_c[i] != 0:
        if s_c[i] == quote_c:
            in_quote = not in_quote
        elif (not in_quote) and s_c[i] == split_c:
            l.append(s[begin_token: i])
            begin_token = i + 1
        i += 1
    l.append(s[begin_token:])
    if in_quote:
        raise ValueError, "unmatched quote"
    return l
