def align_to_haplotype(self, this_haplotype, haplotypes, prefix, suffix,
reads, contig, ref_start):
"""Align reads to a given haplotype, not necessarily the reference.
Align reads to a graph of haplotypes, reporting the alignments relative
to a specific haplotype. This allows treating any alternate allele as
the reference.
Args:
this_haplotype: string. Sequence of the haplotype to treat as reference,
reporting alignments according to its coordinates.
haplotypes: list of strings. All haplotypes to use in the graph, including
this_haplotype.
prefix: string. Sequence to the left of where the haplotypes differ.
suffix: string. Sequence to the right of where the haplotypes differ.
reads: reads to align.
contig: string. Name of the 'reference' to report in read alignments.
ref_start: integer. Start position of the region to report in read
alignments. This should mark the beginning of the prefix sequence.
Returns:
Reads. Realigned and reported relative to the chosen haplotype.
"""
if not reads:
return []
fast_pass_realigner = fast_pass_aligner.FastPassAligner()
aln_config = self.config.aln_config
aln_config.read_size = len(reads[0].aligned_sequence)
aln_config.force_alignment = True
fast_pass_realigner.set_options(aln_config)
fast_pass_realigner.set_reference(prefix + this_haplotype + suffix)
fast_pass_realigner.set_ref_start(contig, ref_start)
# Testing found that when the prefix and suffix both go right up to the
# ref/alt variants, the alignment does not work well, so a margin of 100
# bases on each side of the variant are used here to pad each
# haplotype with enough sequence to align against. While some further
# testing showed this could be reduced, 100 is the only value that has been
# tested with a full training experiment.
central_allele_margin = min(len(prefix), len(suffix), 100)
fast_pass_realigner.set_ref_prefix_len(
len(prefix) - central_allele_margin)
fast_pass_realigner.set_ref_suffix_len(
len(suffix) - central_allele_margin)
extended_haplotypes = [
prefix + target + suffix for target in haplotypes
]
fast_pass_realigner.set_haplotypes(extended_haplotypes)
return fast_pass_realigner.realign_reads(reads)
def call_fast_pass_aligner(self, assembled_region):
"""Helper function to call fast pass aligner module."""
if not assembled_region.reads:
return []
contig = assembled_region.region.reference_name
ref_start = max(
0,
min(assembled_region.read_span.start,
assembled_region.region.start) - _REF_ALIGN_MARGIN)
ref_end = min(
self.ref_reader.contig(contig).n_bases,
max(assembled_region.read_span.end, assembled_region.region.end) +
_REF_ALIGN_MARGIN)
ref_prefix = self.ref_reader.query(
ranges.make_range(contig, ref_start,
assembled_region.region.start))
ref = self.ref_reader.query(assembled_region.region)
# If we can't create the ref suffix then return the original alignments.
if ref_end <= assembled_region.region.end:
return assembled_region.reads
else:
ref_suffix = self.ref_reader.query(
ranges.make_range(contig, assembled_region.region.end,
ref_end))
ref_seq = ref_prefix + ref + ref_suffix
fast_pass_realigner = fast_pass_aligner.FastPassAligner()
# Read sizes may vary. We need this for realigner initialization and sanity
# checks.
self.config.aln_config.read_size = len(
assembled_region.reads[0].aligned_sequence)
self.config.aln_config.force_alignment = False
fast_pass_realigner.set_normalize_reads(self.config.normalize_reads)
fast_pass_realigner.set_options(self.config.aln_config)
fast_pass_realigner.set_reference(ref_seq)
fast_pass_realigner.set_ref_start(contig, ref_start)
fast_pass_realigner.set_ref_prefix_len(len(ref_prefix))
fast_pass_realigner.set_ref_suffix_len(len(ref_suffix))
fast_pass_realigner.set_haplotypes([
ref_prefix + target + ref_suffix
for target in assembled_region.haplotypes
])
return fast_pass_realigner.realign_reads(assembled_region.reads)
