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