-
Notifications
You must be signed in to change notification settings - Fork 31
/
varsim_somatic.py
executable file
·232 lines (202 loc) · 14.2 KB
/
varsim_somatic.py
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
#!/usr/bin/env python
# this is a temporary attempt to get a workable somatic workflow
import argparse
import os
import sys
import subprocess
import logging
import time
import utils
from utils import MY_DIR, check_java, makedirs, get_version
from varsim import monitor_processes, check_executable, run_vcfstats, run_randvcf, RandVCFOptions
VARSIM_PY = os.path.join(MY_DIR, "varsim.py")
def varsim_somatic_main():
main_parser = argparse.ArgumentParser(description="VarSim: somatic workflow",
formatter_class=argparse.ArgumentDefaultsHelpFormatter)
main_parser.add_argument("--out_dir", metavar="Out directory", help="Output directory",
default="somatic_out")
main_parser.add_argument("--work_dir", metavar="Work directory", help="Work directory",
default="somatic_work")
main_parser.add_argument("--log_dir", metavar="Log directory", help="Directory to log to",
default="somatic_log")
main_parser.add_argument("--reference", metavar="FASTA", help="Reference genome", required=True, type=file)
main_parser.add_argument("--seed", metavar="INT", help="Random number seed", type=int, default=0)
main_parser.add_argument("--sex", metavar="Sex", help="Sex of the person (MALE/FEMALE)", required=False, type=str,
choices=["MALE", "FEMALE"], default="MALE")
main_parser.add_argument("--id", metavar="id", help="Sample ID", required=True)
main_parser.add_argument("--simulator", metavar="simulator", help="Read simulator to use", required=False, type=str,
choices=["art", "dwgsim"], default="art")
main_parser.add_argument("--simulator_executable", metavar="PATH",
help="Path to the executable of the read simulator chosen"
, required=True, type=file)
main_parser.add_argument("--varsim_jar", metavar="PATH", help="Path to VarSim.jar (deprecated)", type=file,
default=None,
required=False)
main_parser.add_argument("--read_length", metavar="INT", help="Length of read to simulate", default=100, type=int)
main_parser.add_argument("--nlanes", metavar="INT",
help="Number of lanes to generate, coverage will be divided evenly over the lanes. Simulation is parallized over lanes. Each lane will have its own pair of files",
default=3, type=int)
main_parser.add_argument("--total_coverage", metavar="FLOAT", help="Total coverage to simulate", default=1.0,
type=float)
main_parser.add_argument("--mean_fragment_size", metavar="INT", help="Mean fragment size", default=350,
type=int)
main_parser.add_argument("--sd_fragment_size", metavar="INT", help="Standard deviation of fragment size",
default=50, type=int)
main_parser.add_argument("--force_five_base_encoding", action="store_true", help="Force bases to be ACTGN")
main_parser.add_argument("--filter", action="store_true", help="Only use PASS variants")
main_parser.add_argument("--keep_temp", action="store_true", help="Keep temporary files")
main_parser.add_argument("--java_max_mem", metavar="XMX", help="max java memory", default="10g", type = str)
main_parser.add_argument("--java", metavar="PATH", help="path to java", default="java", type = str)
main_parser.add_argument("--python", metavar="PATH", help="path to python", default="python", type = str)
main_parser.add_argument('--version', action='version', version=get_version())
input_vcf_group = main_parser.add_argument_group("Input VCFs options")
input_vcf_group.add_argument("--cosmic_vcf", metavar="VCF", help="COSMIC database VCF. Need to specify when random COSMIC sampling is enabled.")
input_vcf_group.add_argument("--normal_vcf", metavar="VCF", help="Normal VCF from previous VarSim run", required=True)
input_vcf_group.add_argument("--somatic_vcfs", metavar="VCF", nargs="+", help="Somatic VCF", default=[])
input_vcf_group.add_argument("--merge_priority", choices=["sn", "ns"], help="Priority of merging (lowest first) somatic (s) and normal truth (n).", default="sn")
pipeline_control_group = main_parser.add_argument_group("Pipeline control options. Disable parts of the pipeline.")
pipeline_control_group.add_argument("--disable_rand_vcf", action="store_true", help="Disable RandVCF2VCF somatic")
pipeline_control_group.add_argument("--disable_vcf2diploid", action="store_true", help="Disable vcf2diploid")
pipeline_control_group.add_argument("--disable_sim", action="store_true", help="Disable read simulation")
# RandVCF2VCF seed num_SNP num_INS num_DEL num_MNP num_COMPLEX percent_novel min_length_lim max_length_lim reference_file file.vcf
rand_vcf_group = main_parser.add_argument_group("RandVCF2VCF somatic options")
rand_vcf_group.add_argument("--som_num_snp", metavar="INT", help="Number of somatic SNPs", default=9000, type=int)
rand_vcf_group.add_argument("--som_num_ins", metavar="INT", help="Number of somatic insertions", default=1000,
type=int)
rand_vcf_group.add_argument("--som_num_del", metavar="INT", help="Number of somatic deletions", default=1000,
type=int)
rand_vcf_group.add_argument("--som_num_mnp", metavar="INT", help="Number of somatic MNPs", default=100, type=int)
rand_vcf_group.add_argument("--som_num_complex", metavar="INT", help="Number of somatic complex variants",
default=100, type=int)
# rand_vcf_group.add_argument("--som_percent_novel", metavar="percent_novel", help="Percent novel", default=0, type=float)
rand_vcf_group.add_argument("--som_min_length_lim", metavar="INT", help="Min length lim", default=0,
type=int)
rand_vcf_group.add_argument("--som_max_length_lim", metavar="INT", help="Max length lim", default=49,
type=int)
# rand_vcf_group.add_argument("--som_vcf", metavar="in_vcf", help="Input somatic variant database VCF", type=file, required=False)
rand_vcf_group.add_argument("--som_prop_het", metavar="FLOAT", help="Proportion of somatic heterozygous variants",
default=1.0, type=float)
rand_vcf_group.add_argument("--sv_insert_seq", metavar="FILE",
help="Path to file containing concatenation of real insertion sequences", type=file,
required=True)
dwgsim_group = main_parser.add_argument_group("DWGSIM options")
dwgsim_group.add_argument("--dwgsim_start_e", metavar="first_base_error_rate", help="Error rate on the first base",
default=0.0001, type=float)
dwgsim_group.add_argument("--dwgsim_end_e", metavar="last_base_error_rate", help="Error rate on the last base",
default=0.0015, type=float)
dwgsim_group.add_argument("--dwgsim_options", help="DWGSIM command-line options", default="", required=False)
art_group = main_parser.add_argument_group("ART options")
art_group.add_argument("--profile_1", metavar="profile_file1", help="Profile for first end", default=None, type=file)
art_group.add_argument("--profile_2", metavar="profile_file2", help="Profile for second end", default=None, type=file)
art_group.add_argument("--art_options", help="ART command-line options", default="", required=False)
args = main_parser.parse_args()
args.java = utils.get_java(args.java)
check_java(args.java)
utils.JAVA_XMX = utils.JAVA_XMX + args.java_max_mem
makedirs([args.log_dir, args.out_dir])
FORMAT = '%(levelname)s %(asctime)-15s %(name)-20s %(message)s'
logging.basicConfig(filename=os.path.join(args.log_dir, "varsim.log"), filemode="w", level=logging.DEBUG, format=FORMAT)
logger = logging.getLogger(varsim_somatic_main.__name__)
if not args.disable_sim:
if not args.simulator_executable:
logger.error("Please specify %s binary with --simulator_executable option" % args.simulator)
sys.exit(os.EX_USAGE)
check_executable(args.simulator_executable.name)
t_s = time.time()
cosmic_sampled_vcfs = []
if not args.disable_rand_vcf:
if not args.cosmic_vcf:
logger.error("COSMIC database VCF not specified using --cosmic_vcf")
sys.exit(os.EX_USAGE)
rand_vcf_stdout = open(os.path.join(args.out_dir, "random.cosmic.vcf"), "w")
rand_vcf_stderr = open(os.path.join(args.log_dir, "random.cosmic.err"), "w")
cosmic_sampled_vcfs = [rand_vcf_stdout.name]
# Not able to support novel yet for COSMIC variants
randvcf_options = RandVCFOptions(args.som_num_snp, args.som_num_ins, args.som_num_del, args.som_num_mnp, args.som_num_complex, 0, args.som_min_length_lim, args.som_max_length_lim, args.som_prop_het)
run_randvcf(os.path.realpath(args.cosmic_vcf), rand_vcf_stdout, rand_vcf_stderr, args.seed, args.sex, randvcf_options, args.reference.name, args.java)
normal_vcfs = [args.normal_vcf]
somatic_vcfs = cosmic_sampled_vcfs + args.somatic_vcfs
fixed_somatic_vcfs = []
if somatic_vcfs:
vcfs_dir = os.path.join(args.out_dir, "somatic_vcfs")
makedirs([vcfs_dir])
count = 0
for index, vcf in enumerate(somatic_vcfs):
copied_vcf = os.path.join(vcfs_dir, "%d.vcf" % index)
logger.info("Copying somatic VCF %s to %s and adding VARSIMSOMATIC id to entries if missing" % (vcf, copied_vcf))
with open(vcf, "r") as vcf_fd, open(copied_vcf, "w") as copied_vcf_fd:
for line in vcf_fd:
if line.startswith("#"):
copied_vcf_fd.write(line)
else:
line_fields = line.split("\t")
line_fields[2] = ("VARSIMSOMATIC%d" % count) if line_fields[2] == "." else ("%s,VARSIMSOMATIC%d" % (line_fields[2], count))
copied_vcf_fd.write("\t".join(line_fields))
count += 1
fixed_somatic_vcfs.append(copied_vcf)
vcf_files = (fixed_somatic_vcfs + normal_vcfs) if args.merge_priority == "sn" else (normal_vcfs + fixed_somatic_vcfs)
vcf_files = map(os.path.realpath, filter(None, vcf_files))
processes = run_vcfstats(vcf_files, args.out_dir, args.log_dir, args.java)
# Run VarSim
varsim_stdout = open(os.path.join(args.log_dir, "som_varsim.out"), "w")
varsim_stderr = open(os.path.join(args.log_dir, "som_varsim.log"), "w")
vcf_arg_list = ["--vcfs"] + vcf_files
# need to fix the store true ones
filter_arg_list = ["--filter"] if args.filter else []
disable_sim_arg_list = ["--disable_sim"] if args.disable_sim else []
force_five_base_encoding_arg_list = ["--force_five_base_encoding"] if args.force_five_base_encoding else []
keep_temp_arg_list = ["--keep_temp"] if args.keep_temp else []
profile_1_arg_list = ["--profile_1", args.profile_1.name] if args.profile_1 is not None else []
profile_2_arg_list = ["--profile_2", args.profile_2.name] if args.profile_2 is not None else []
other_varsim_opts = []
if args.simulator == "dwgsim":
other_varsim_opts = ["--dwgsim_start_e", str(args.dwgsim_start_e), "--dwgsim_end_e", str(args.dwgsim_end_e)]
if args.dwgsim_options: other_varsim_opts += ["--dwgsim_options", str(args.dwgsim_options)]
elif args.simulator == "art" and args.art_options:
other_varsim_opts += ["--art_options", args.art_options]
args.python = utils.get_python(args.python)
varsim_command = [args.python, os.path.realpath(VARSIM_PY),
"--out_dir", str(os.path.realpath(args.out_dir)),
"--work_dir", str(os.path.realpath(args.work_dir)),
"--log_dir", str(os.path.realpath(os.path.join(args.log_dir, "varsim"))),
"--reference", str(os.path.realpath(args.reference.name)),
"--seed", str(args.seed),
"--sex", str(args.sex),
"--id", str(args.id),
"--simulator", str(args.simulator),
"--simulator_executable", str(args.simulator_executable.name),
"--read_length", str(args.read_length),
"--nlanes", str(args.nlanes),
"--total_coverage", str(args.total_coverage),
"--mean_fragment_size", str(args.mean_fragment_size),
"--sd_fragment_size", str(args.sd_fragment_size),
"--disable_rand_vcf",
"--disable_rand_dgv",
"--sv_insert_seq", args.sv_insert_seq.name] + other_varsim_opts + vcf_arg_list + filter_arg_list + disable_sim_arg_list \
+ force_five_base_encoding_arg_list + keep_temp_arg_list + profile_1_arg_list + profile_2_arg_list
varsim_command = " ".join(varsim_command)
p_varsim = subprocess.Popen(varsim_command, stdout=varsim_stdout, stderr=varsim_stderr, shell=True)
logger.info("Executing command " + varsim_command + " with pid " + str(p_varsim.pid))
processes.append(p_varsim)
processes = monitor_processes(processes)
# Split the tumor truth VCF into normal variants and somatic variants
tumor_vcf = os.path.realpath(os.path.join(args.out_dir, "%s.truth.vcf" % args.id))
normal_vcf = os.path.join(args.out_dir, "%s_norm.vcf" % args.id)
somatic_vcf = os.path.join(args.out_dir, "%s_somatic.vcf" % args.id)
logger.info("Splitting the truth VCF %s into normal and somatic VCFs" % tumor_vcf)
with open(tumor_vcf, "r") as tumor_truth_fd, \
open(normal_vcf, "w") as normal_vcf_fd, \
open(somatic_vcf, "w") as somatic_vcf_fd:
for line in tumor_truth_fd:
if line.startswith("#"):
somatic_vcf_fd.write(line)
normal_vcf_fd.write(line)
continue
if line.find("VARSIMSOMATIC") >= 0:
somatic_vcf_fd.write(line)
else:
normal_vcf_fd.write(line)
run_vcfstats([normal_vcf, somatic_vcf], args.out_dir, args.log_dir, args.java)
logger.info("Done! (%g hours)" % ((time.time() - t_s) / 3600.0))
if __name__ == "__main__":
varsim_somatic_main()