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in silico deletion script: hound_isd_bed #43
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#!/usr/bin/env python | ||
# Copyright 2017 Calico LLC | ||
# | ||
# Licensed under the Apache License, Version 2.0 (the "License"); | ||
# you may not use this file except in compliance with the License. | ||
# You may obtain a copy of the License at | ||
# | ||
# https://www.apache.org/licenses/LICENSE-2.0 | ||
# | ||
# Unless required by applicable law or agreed to in writing, software | ||
# distributed under the License is distributed on an "AS IS" BASIS, | ||
# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. | ||
# See the License for the specific language governing permissions and | ||
# limitations under the License. | ||
# ========================================================================= | ||
from optparse import OptionParser | ||
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||
import json | ||
import os | ||
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import h5py | ||
import numpy as np | ||
import pandas as pd | ||
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from baskerville import bed | ||
from baskerville import dataset | ||
from baskerville import dna | ||
from baskerville import seqnn | ||
from baskerville import snps | ||
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""" | ||
hound_isd_bed.py | ||
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Perform an in silico deletion mutagenesis of sequences in a BED file. | ||
""" | ||
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def main(): | ||
usage = "usage: %prog [options] <params_file> <model_file> <bed_file>" | ||
parser = OptionParser(usage) | ||
parser.add_option( | ||
"-d", | ||
dest="mut_down", | ||
default=0, | ||
type="int", | ||
help="Nucleotides downstream of center sequence to mutate [Default: %default]", | ||
) | ||
parser.add_option( | ||
"-f", | ||
dest="genome_fasta", | ||
default=None, | ||
help="Genome FASTA for sequences [Default: %default]", | ||
) | ||
parser.add_option( | ||
"-l", | ||
dest="mut_len", | ||
default=0, | ||
type="int", | ||
help="Length of center sequence to mutate [Default: %default]", | ||
) | ||
parser.add_option( | ||
"-s", | ||
dest="del_len", | ||
default=1, | ||
type="int", | ||
help="Deletion size for ISD [Default: %default]", | ||
) | ||
parser.add_option( | ||
"-o", | ||
dest="out_dir", | ||
default="sat_del", | ||
help="Output directory [Default: %default]", | ||
) | ||
parser.add_option( | ||
"-p", | ||
dest="processes", | ||
default=None, | ||
type="int", | ||
help="Number of processes, passed by multi script", | ||
) | ||
parser.add_option( | ||
"--rc", | ||
dest="rc", | ||
default=False, | ||
action="store_true", | ||
help="Ensemble forward and reverse complement predictions [Default: %default]", | ||
) | ||
parser.add_option( | ||
"--shifts", | ||
dest="shifts", | ||
default="0", | ||
help="Ensemble prediction shifts [Default: %default]", | ||
) | ||
parser.add_option( | ||
"--stats", | ||
dest="snp_stats", | ||
default="logSUM", | ||
help="Comma-separated list of stats to save. [Default: %default]", | ||
) | ||
parser.add_option( | ||
"-t", | ||
dest="targets_file", | ||
default=None, | ||
type="str", | ||
help="File specifying target indexes and labels in table format", | ||
) | ||
parser.add_option( | ||
"-u", | ||
dest="mut_up", | ||
default=0, | ||
type="int", | ||
help="Nucleotides upstream of center sequence to mutate [Default: %default]", | ||
) | ||
parser.add_option( | ||
"--untransform_old", | ||
dest="untransform_old", | ||
default=False, | ||
action="store_true", | ||
help="Untransform old models [Default: %default]", | ||
) | ||
(options, args) = parser.parse_args() | ||
|
||
if len(args) == 3: | ||
# single worker | ||
params_file = args[0] | ||
model_file = args[1] | ||
bed_file = args[2] | ||
else: | ||
parser.error("Must provide parameter and model files and BED file") | ||
|
||
if not os.path.isdir(options.out_dir): | ||
os.mkdir(options.out_dir) | ||
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options.shifts = [int(shift) for shift in options.shifts.split(",")] | ||
options.snp_stats = [snp_stat for snp_stat in options.snp_stats.split(",")] | ||
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if options.mut_up > 0 or options.mut_down > 0: | ||
options.mut_len = options.mut_up + options.mut_down | ||
else: | ||
assert options.mut_len > 0 | ||
options.mut_up = options.mut_len // 2 | ||
options.mut_down = options.mut_len - options.mut_up | ||
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################################################################# | ||
# read parameters and targets | ||
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# read model parameters | ||
with open(params_file) as params_open: | ||
params = json.load(params_open) | ||
params_model = params["model"] | ||
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# read targets | ||
if options.targets_file is None: | ||
parser.error("Must provide targets file to clarify stranded datasets") | ||
targets_df = pd.read_csv(options.targets_file, sep="\t", index_col=0) | ||
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# handle strand pairs | ||
if "strand_pair" in targets_df.columns: | ||
# prep strand | ||
targets_strand_df = dataset.targets_prep_strand(targets_df) | ||
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# set strand pairs (using new indexing) | ||
orig_new_index = dict(zip(targets_df.index, np.arange(targets_df.shape[0]))) | ||
targets_strand_pair = np.array( | ||
[orig_new_index[ti] for ti in targets_df.strand_pair] | ||
) | ||
params_model["strand_pair"] = [targets_strand_pair] | ||
|
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# construct strand sum transform | ||
strand_transform = dataset.make_strand_transform(targets_df, targets_strand_df) | ||
else: | ||
targets_strand_df = targets_df | ||
strand_transform = None | ||
num_targets = targets_strand_df.shape[0] | ||
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################################################################# | ||
# setup model | ||
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seqnn_model = seqnn.SeqNN(params_model) | ||
seqnn_model.restore(model_file) | ||
seqnn_model.build_slice(targets_df.index) | ||
seqnn_model.build_ensemble(options.rc) | ||
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################################################################# | ||
# sequence dataset | ||
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# read sequences from BED | ||
seqs_dna, seqs_coords = bed.make_bed_seqs( | ||
bed_file, options.genome_fasta, params_model["seq_length"], stranded=True | ||
) | ||
num_seqs = len(seqs_dna) | ||
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# determine mutation region limits | ||
seq_mid = params_model["seq_length"] // 2 | ||
mut_start = seq_mid - options.mut_up | ||
mut_end = mut_start + options.mut_len | ||
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model_stride = seqnn_model.model_strides[0] | ||
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################################################################# | ||
# setup output | ||
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scores_h5_file = "%s/scores.h5" % options.out_dir | ||
if os.path.isfile(scores_h5_file): | ||
os.remove(scores_h5_file) | ||
scores_h5 = h5py.File(scores_h5_file, "w") | ||
scores_h5.create_dataset("seqs", dtype="bool", shape=(num_seqs, options.mut_len, 4)) | ||
for snp_stat in options.snp_stats: | ||
scores_h5.create_dataset( | ||
snp_stat, dtype="float16", shape=(num_seqs, options.mut_len, 1, num_targets) | ||
) | ||
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# store mutagenesis sequence coordinates | ||
scores_chr = [] | ||
scores_start = [] | ||
scores_end = [] | ||
scores_strand = [] | ||
for seq_chr, seq_start, seq_end, seq_strand in seqs_coords: | ||
scores_chr.append(seq_chr) | ||
scores_strand.append(seq_strand) | ||
if seq_strand == "+": | ||
score_start = seq_start + mut_start | ||
score_end = score_start + options.mut_len | ||
else: | ||
score_end = seq_end - mut_start | ||
score_start = score_end - options.mut_len | ||
scores_start.append(score_start) | ||
scores_end.append(score_end) | ||
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scores_h5.create_dataset("chr", data=np.array(scores_chr, dtype="S")) | ||
scores_h5.create_dataset("start", data=np.array(scores_start)) | ||
scores_h5.create_dataset("end", data=np.array(scores_end)) | ||
scores_h5.create_dataset("strand", data=np.array(scores_strand, dtype="S")) | ||
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################################################################# | ||
# predict scores, write output | ||
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# make list of shifts for reference stitching | ||
ref_shifts = [] | ||
for shift in options.shifts: | ||
ref_shifts.append(shift) | ||
ref_shifts.append(shift - options.del_len) | ||
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for si, seq_dna in enumerate(seqs_dna): | ||
print("Predicting %d" % si, flush=True) | ||
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# 1 hot code DNA | ||
ref_1hot = dna.dna_1hot(seq_dna) | ||
ref_1hot = np.expand_dims(ref_1hot, axis=0) | ||
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# save sequence | ||
scores_h5["seqs"][si] = ref_1hot[0, mut_start:mut_end].astype("bool") | ||
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# predict reference | ||
ref_preds = [] | ||
for shift in ref_shifts: | ||
# shift sequence and predict | ||
ref_1hot_shift = dna.hot1_augment(ref_1hot, shift=shift) | ||
ref_preds_shift = seqnn_model.predict_transform( | ||
ref_1hot_shift, | ||
targets_df, | ||
strand_transform, | ||
options.untransform_old, | ||
) | ||
ref_preds.append(ref_preds_shift) | ||
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# increment by deletion size | ||
for mi in range(mut_start, mut_end, options.del_len): | ||
# for each nucleotide | ||
# copy and modify | ||
alt_1hot = np.copy(ref_1hot) | ||
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# left-matched shift: delete 1 nucleotide at position mi | ||
dna.hot1_delete(alt_1hot[0], mi, options.del_len) | ||
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# predict alternate | ||
alt_preds = [] | ||
for shift in options.shifts: | ||
# shift sequence and predict | ||
alt_1hot_shift = dna.hot1_augment(alt_1hot, shift=shift) | ||
alt_preds_shift = seqnn_model.predict_transform( | ||
alt_1hot_shift, | ||
targets_df, | ||
strand_transform, | ||
options.untransform_old, | ||
) | ||
alt_preds.append(alt_preds_shift) | ||
alt_preds = np.array(alt_preds) | ||
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out_seq_len = alt_preds.shape[1] | ||
out_seq_center = out_seq_len // 2 | ||
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# stitch reference predictions at the mutated nucleotide | ||
snp_seq_bin = out_seq_center + (mi - options.mut_up) // model_stride | ||
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ref_preds_stitch = snps.stitch_preds(ref_preds, options.shifts, snp_seq_bin) | ||
ref_preds_stitch = np.array(ref_preds_stitch) | ||
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ism_scores = snps.compute_scores( | ||
ref_preds_stitch, alt_preds, options.snp_stats, None | ||
) | ||
for snp_stat in options.snp_stats: | ||
scores_h5[snp_stat][si, mi - mut_start, 0] = ism_scores[snp_stat] | ||
There was a problem hiding this comment. Choose a reason for hiding this commentThe reason will be displayed to describe this comment to others. Learn more. By dropping the 3rd axis, you can remove the "0]" here. |
||
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# close output HDF5 | ||
scores_h5.close() | ||
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################################################################################ | ||
# __main__ | ||
################################################################################ | ||
if __name__ == "__main__": | ||
main() |
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"del_size" maybe so -s matches the first letter?