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# Copyright 2020 Google LLC. |
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# |
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# Redistribution and use in source and binary forms, with or without |
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# modification, are permitted provided that the following conditions |
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# are met: |
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# |
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# 1. Redistributions of source code must retain the above copyright notice, |
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# this list of conditions and the following disclaimer. |
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# |
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# 2. Redistributions in binary form must reproduce the above copyright |
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# notice, this list of conditions and the following disclaimer in the |
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# documentation and/or other materials provided with the distribution. |
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# |
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# 3. Neither the name of the copyright holder nor the names of its |
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# contributors may be used to endorse or promote products derived from this |
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# software without specific prior written permission. |
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# |
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# THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS" |
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# AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE |
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# IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE |
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# ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT HOLDER OR CONTRIBUTORS BE |
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# LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR |
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# CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF |
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# SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS |
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# INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN |
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# CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) |
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# ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF THE |
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# POSSIBILITY OF SUCH DAMAGE. |
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"""Step one of DeepTrio: creates tf.Example protos for training/calling.""" |
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import os |
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from absl import app |
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from absl import flags |
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from deeptrio import dt_constants |
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from deepvariant import logging_level |
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from deepvariant import make_examples_core |
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from deepvariant import make_examples_options |
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from deepvariant.protos import deepvariant_pb2 |
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from third_party.nucleus.io.python import hts_verbose |
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from third_party.nucleus.util import errors |
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from third_party.nucleus.util import proto_utils |
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# Sentinel command line flag value indicating no downsampling should occur. |
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NO_DOWNSAMPLING = 0.0 |
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MAIN_SAMPLE_INDEX = 1 # 1 is the child of the trio. |
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FLAGS = flags.FLAGS |
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# Adopt more general flags from make_examples_options. |
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flags.adopt_module_key_flags(make_examples_options) |
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# Flags related to samples in DeepTrio: |
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SAMPLE_NAME_TO_TRAIN_ = flags.DEFINE_string( |
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'sample_name_to_train', |
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None, |
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( |
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'Optional - if not set, default to the value in --sample_name, i.e. the' |
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' child. The default is set to be backward compatible. If set, it has' |
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' to match one of --sample_name, --sample_name_parent1, or' |
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' --sample_name_parent2. Only used for training. When run in calling' |
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' mode, this is unused because examples are generated for all 3 samples' |
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' together.' |
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), |
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) |
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READS_ = flags.DEFINE_string( |
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'reads', |
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None, |
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( |
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'Required. Aligned, sorted, indexed BAM file containing reads from the ' |
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'child of the trio. ' |
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'Should be aligned to a reference genome compatible with --ref. ' |
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'Can provide multiple BAMs (comma-separated).' |
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), |
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) |
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READS_PARENT1_ = flags.DEFINE_string( |
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'reads_parent1', |
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None, |
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( |
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'Required. Aligned, sorted, indexed BAM file containing reads from' |
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' parent 1 of the trio. Should be aligned to a reference genome' |
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' compatible with --ref. Can provide multiple BAMs (comma-separated).' |
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), |
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) |
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READS_PARENT2_ = flags.DEFINE_string( |
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'reads_parent2', |
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None, |
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( |
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'Aligned, sorted, indexed BAM file containing reads from parent 2 of' |
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' the trio. Should be aligned to a reference genome compatible with' |
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' --ref. Can provide multiple BAMs (comma-separated).' |
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), |
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) |
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DOWNSAMPLE_FRACTION_CHILD_ = flags.DEFINE_float( |
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'downsample_fraction_child', |
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NO_DOWNSAMPLING, |
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'If not ' |
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+ str(NO_DOWNSAMPLING) |
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+ ' must be a value between 0.0 and 1.0. ' |
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'Reads will be kept (randomly) with a probability of downsample_fraction ' |
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'from the input child BAM. This argument makes it easy to create examples ' |
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'as though the input BAM had less coverage.', |
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) |
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DOWNSAMPLE_FRACTION_PARENTS_ = flags.DEFINE_float( |
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'downsample_fraction_parents', |
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NO_DOWNSAMPLING, |
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'If not ' |
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+ str(NO_DOWNSAMPLING) |
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+ ' must be a value between 0.0 and 1.0. ' |
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'Reads will be kept (randomly) with a probability of downsample_fraction ' |
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'from the input parent BAMs. This argument makes it easy to create examples' |
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' as though the input BAMs had less coverage.', |
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) |
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SAMPLE_NAME_ = flags.DEFINE_string( |
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'sample_name', |
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'', |
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( |
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'Child sample name to use for our sample_name in the output' |
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' Variant/DeepVariantCall protos. If not specified, will be inferred' |
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' from the header information from --reads.' |
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), |
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) |
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SAMPLE_NAME_PARENT1_ = flags.DEFINE_string( |
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'sample_name_parent1', |
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'', |
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( |
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'Parent1 Sample name to use for our sample_name in the output' |
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' Variant/DeepVariantCall protos. If not specified, will be inferred' |
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' from the header information from --reads_parent1.' |
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), |
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) |
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SAMPLE_NAME_PARENT2_ = flags.DEFINE_string( |
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'sample_name_parent2', |
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'', |
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( |
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'Parent2 Sample name to use for our sample_name in the output' |
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' Variant/DeepVariantCall protos. If not specified, will be inferred' |
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' from the header information from --reads_parent2.' |
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), |
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) |
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PILEUP_IMAGE_HEIGHT_PARENT_ = flags.DEFINE_integer( |
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'pileup_image_height_parent', |
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0, |
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'Height for the parent pileup image. If 0, uses the default height', |
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) |
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PILEUP_IMAGE_HEIGHT_CHILD_ = flags.DEFINE_integer( |
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'pileup_image_height_child', |
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0, |
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'Height for the child pileup image. If 0, uses the default height', |
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) |
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PROPOSED_VARIANTS_CHILD_ = flags.DEFINE_string( |
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'proposed_variants_child', |
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None, |
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( |
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'(Only used when --variant_caller=vcf_candidate_importer.) ' |
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'Tabix-indexed VCF file containing the proposed positions and alts for ' |
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'`vcf_candidate_importer` for the child. The GTs will be ignored.' |
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), |
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) |
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PROPOSED_VARIANTS_PARENT1_ = flags.DEFINE_string( |
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'proposed_variants_parent1', |
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None, |
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( |
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'(Only used when --variant_caller=vcf_candidate_importer.) ' |
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'Tabix-indexed VCF file containing the proposed positions and alts for ' |
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'`vcf_candidate_importer` for the parent 1. The GTs will be ignored.' |
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), |
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) |
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PROPOSED_VARIANTS_PARENT2_ = flags.DEFINE_string( |
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'proposed_variants_parent2', |
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None, |
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( |
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'(Only used when --variant_caller=vcf_candidate_importer.) ' |
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'Tabix-indexed VCF file containing the proposed positions and alts for ' |
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'`vcf_candidate_importer` for the parent 2. The GTs will be ignored.' |
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), |
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) |
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# We are using this flag for determining intervals for both child and parent |
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# models. In the future, we can consider extending into 3 samples. |
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CANDIDATE_POSITIONS_ = flags.DEFINE_string( |
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'candidate_positions', |
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None, |
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( |
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'Path to the binary file containing candidate positions used for ' |
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'make_examples partitioning by candidates. Currently this ' |
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'is only the child positions.' |
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), |
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) |
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_SKIP_PARENT_CALLING = flags.DEFINE_bool( |
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'skip_parent_calling', |
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False, |
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'If True, parents will not be called. Default is False.', |
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) |
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# Change any flag defaults that differ for DeepTrio. |
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FLAGS.set_default('vsc_min_fraction_multiplier', 0.67) |
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def trio_samples_from_flags(add_flags=True, flags_obj=None): |
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"""Collects sample-related options into a list of samples.""" |
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# Sample-specific options. |
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child_sample_name = make_examples_core.assign_sample_name( |
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sample_name_flag=SAMPLE_NAME_.value, reads_filenames=READS_.value |
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) |
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parent1_sample_name = make_examples_core.assign_sample_name( |
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sample_name_flag=SAMPLE_NAME_PARENT1_.value, |
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reads_filenames=READS_PARENT1_.value, |
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) |
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parent2_sample_name = make_examples_core.assign_sample_name( |
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sample_name_flag=SAMPLE_NAME_PARENT2_.value, |
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reads_filenames=READS_PARENT2_.value, |
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) |
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parent1_options = deepvariant_pb2.SampleOptions( |
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role='parent1', |
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name=parent1_sample_name, |
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variant_caller_options=make_examples_core.make_vc_options( |
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sample_name=parent1_sample_name, flags_obj=flags_obj |
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), |
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order=[0, 1, 2], |
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pileup_height=dt_constants.PILEUP_DEFAULT_HEIGHT_PARENT, |
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skip_output_generation=_SKIP_PARENT_CALLING.value, |
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) |
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child_options = deepvariant_pb2.SampleOptions( |
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role='child', |
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name=child_sample_name, |
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variant_caller_options=make_examples_core.make_vc_options( |
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sample_name=child_sample_name, flags_obj=flags_obj |
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), |
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order=[0, 1, 2], |
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pileup_height=dt_constants.PILEUP_DEFAULT_HEIGHT_CHILD, |
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) |
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parent2_options = deepvariant_pb2.SampleOptions( |
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role='parent2', |
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name=parent2_sample_name, |
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variant_caller_options=make_examples_core.make_vc_options( |
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sample_name=parent2_sample_name, flags_obj=flags_obj |
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), |
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# Swap the two parents when calling on parent2. |
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order=[2, 1, 0], |
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pileup_height=dt_constants.PILEUP_DEFAULT_HEIGHT_PARENT, |
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skip_output_generation=_SKIP_PARENT_CALLING.value, |
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) |
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# If --sample_name_to_train is not set, train on the child. |
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# This is for backward compatibility. |
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sample_role_to_train = 'child' |
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if add_flags: |
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if READS_.value: |
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child_options.reads_filenames.extend(READS_.value.split(',')) |
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if READS_PARENT1_.value: |
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parent1_options.reads_filenames.extend(READS_PARENT1_.value.split(',')) |
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if READS_PARENT2_.value: |
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parent2_options.reads_filenames.extend(READS_PARENT2_.value.split(',')) |
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if CANDIDATE_POSITIONS_.value: |
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child_options.candidate_positions = CANDIDATE_POSITIONS_.value |
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if PROPOSED_VARIANTS_CHILD_.value: |
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child_options.proposed_variants_filename = PROPOSED_VARIANTS_CHILD_.value |
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if PROPOSED_VARIANTS_PARENT1_.value: |
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parent1_options.proposed_variants_filename = ( |
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PROPOSED_VARIANTS_PARENT1_.value |
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) |
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if PROPOSED_VARIANTS_PARENT2_.value: |
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parent2_options.proposed_variants_filename = ( |
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PROPOSED_VARIANTS_PARENT2_.value |
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) |
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if DOWNSAMPLE_FRACTION_CHILD_.value != NO_DOWNSAMPLING: |
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child_options.downsample_fraction = DOWNSAMPLE_FRACTION_CHILD_.value |
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if DOWNSAMPLE_FRACTION_PARENTS_.value != NO_DOWNSAMPLING: |
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parent1_options.downsample_fraction = DOWNSAMPLE_FRACTION_PARENTS_.value |
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parent2_options.downsample_fraction = DOWNSAMPLE_FRACTION_PARENTS_.value |
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if PILEUP_IMAGE_HEIGHT_CHILD_.value: |
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child_options.pileup_height = PILEUP_IMAGE_HEIGHT_CHILD_.value |
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if PILEUP_IMAGE_HEIGHT_PARENT_.value: |
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parent1_options.pileup_height = ( |
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parent2_options.pileup_height |
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) = PILEUP_IMAGE_HEIGHT_PARENT_.value |
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if SAMPLE_NAME_TO_TRAIN_.value: |
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if SAMPLE_NAME_TO_TRAIN_.value == SAMPLE_NAME_.value: |
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sample_role_to_train = child_options.role |
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elif SAMPLE_NAME_TO_TRAIN_.value == SAMPLE_NAME_PARENT1_.value: |
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sample_role_to_train = parent1_options.role |
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else: |
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errors.log_and_raise( |
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( |
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'--sample_name_to_train must match either --sample_name or ' |
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'--sample_name_parent1, or it can be unset to default to ' |
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'--sample_name.' |
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), |
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errors.CommandLineError, |
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) |
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# Ordering here determines the default order of samples, and when a sample |
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# above has a custom .order, then this is the list those indices refer to. |
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samples_in_order = [parent1_options, child_options, parent2_options] |
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return samples_in_order, sample_role_to_train |
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def default_options(add_flags=True, flags_obj=None): |
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"""Creates a MakeExamplesOptions proto populated with reasonable defaults. |
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Args: |
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add_flags: bool. defaults to True. If True, we will push the value of |
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certain FLAGS into our options. If False, those option fields are left |
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uninitialized. |
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flags_obj: object. If not None, use as the source of flags, else use global |
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FLAGS. |
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Returns: |
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deepvariant_pb2.MakeExamplesOptions protobuf. |
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Raises: |
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ValueError: If we observe invalid flag values. |
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""" |
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if not flags_obj: |
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flags_obj = FLAGS |
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samples_in_order, sample_role_to_train = trio_samples_from_flags( |
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add_flags=add_flags, flags_obj=flags_obj |
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) |
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options = make_examples_options.shared_flags_to_options( |
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add_flags=add_flags, |
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flags_obj=flags_obj, |
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samples_in_order=samples_in_order, |
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sample_role_to_train=sample_role_to_train, |
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main_sample_index=MAIN_SAMPLE_INDEX, |
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) |
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if add_flags: |
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options.bam_fname = ( |
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os.path.basename(READS_.value) |
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+ '|' |
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+ ( |
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os.path.basename(READS_PARENT1_.value) |
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if READS_PARENT1_.value |
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else 'None' |
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) |
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+ '|' |
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+ ( |
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os.path.basename(READS_PARENT2_.value) |
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if READS_PARENT2_.value |
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else 'None' |
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) |
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) |
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options.pic_options.sequencing_type = ( |
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deepvariant_pb2.PileupImageOptions.TRIO |
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) |
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if not options.pic_options.height: |
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360 |
options.pic_options.height = dt_constants.PILEUP_DEFAULT_HEIGHT |
|
|
361 |
if not options.pic_options.width: |
|
|
362 |
options.pic_options.width = dt_constants.PILEUP_DEFAULT_WIDTH |
|
|
363 |
|
|
|
364 |
return options |
|
|
365 |
|
|
|
366 |
|
|
|
367 |
def check_options_are_valid(options): |
|
|
368 |
"""Checks that all the options chosen make sense together.""" |
|
|
369 |
|
|
|
370 |
# Check for general flags (shared for DeepVariant and DeepTrio). |
|
|
371 |
make_examples_options.check_options_are_valid( |
|
|
372 |
options, main_sample_index=MAIN_SAMPLE_INDEX |
|
|
373 |
) |
|
|
374 |
|
|
|
375 |
child = options.sample_options[MAIN_SAMPLE_INDEX] |
|
|
376 |
|
|
|
377 |
# Sanity check the sample_names (specific to trio). |
|
|
378 |
if ( |
|
|
379 |
child.variant_caller_options.sample_name == FLAGS.sample_name_parent1 |
|
|
380 |
or child.variant_caller_options.sample_name == FLAGS.sample_name_parent2 |
|
|
381 |
): |
|
|
382 |
errors.log_and_raise( |
|
|
383 |
'The sample_name of the child is the same as one of the parents.', |
|
|
384 |
errors.CommandLineError, |
|
|
385 |
) |
|
|
386 |
|
|
|
387 |
if options.pic_options.alt_aligned_pileup == 'rows': |
|
|
388 |
errors.log_and_raise( |
|
|
389 |
'--alt_aligned_pileup="rows" cannot be used with ' |
|
|
390 |
'DeepTrio because the pileup images would become ' |
|
|
391 |
'too tall for InceptionV3.' |
|
|
392 |
) |
|
|
393 |
|
|
|
394 |
if ( |
|
|
395 |
options.mode == deepvariant_pb2.MakeExamplesOptions.CANDIDATE_SWEEP |
|
|
396 |
and child.candidate_positions is None |
|
|
397 |
): |
|
|
398 |
errors.log_and_raise( |
|
|
399 |
'--candidate_positions is required when --positions_sweep_mode is set.' |
|
|
400 |
) |
|
|
401 |
|
|
|
402 |
|
|
|
403 |
def main(argv=()): |
|
|
404 |
with errors.clean_commandline_error_exit(): |
|
|
405 |
if len(argv) > 1: |
|
|
406 |
errors.log_and_raise( |
|
|
407 |
'Command line parsing failure: make_examples does not accept ' |
|
|
408 |
'positional arguments but some are present on the command line: ' |
|
|
409 |
'"{}".'.format(str(argv)), |
|
|
410 |
errors.CommandLineError, |
|
|
411 |
) |
|
|
412 |
del argv # Unused. |
|
|
413 |
|
|
|
414 |
proto_utils.uses_fast_cpp_protos_or_die() |
|
|
415 |
|
|
|
416 |
logging_level.set_from_flag() |
|
|
417 |
hts_verbose.set(hts_verbose.htsLogLevel.HTS_LOG_WARNING) |
|
|
418 |
|
|
|
419 |
# Set up options; may do I/O. |
|
|
420 |
options = default_options(add_flags=True, flags_obj=FLAGS) |
|
|
421 |
check_options_are_valid(options) |
|
|
422 |
|
|
|
423 |
# Run! |
|
|
424 |
make_examples_core.make_examples_runner(options) |
|
|
425 |
|
|
|
426 |
|
|
|
427 |
if __name__ == '__main__': |
|
|
428 |
flags.mark_flags_as_required([ |
|
|
429 |
'examples', |
|
|
430 |
'mode', |
|
|
431 |
'reads', |
|
|
432 |
'ref', |
|
|
433 |
]) |
|
|
434 |
app.run(main) |