Could not find valid purity and ploidy solution #355
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INFO [2024-03-08 13:27:10] ------------------------------------------------------------
INFO [2024-03-08 13:27:10] PureCN 2.8.1
INFO [2024-03-08 13:27:10] ------------------------------------------------------------
INFO [2024-03-08 13:27:10] Arguments: -tumor.coverage.file /t_c_data/4139_NA_LIB2652_M__S48_sentieon_match_4.1_deduped_coverage_loess.txt.gz -log.ratio -seg.file -vcf.file ../in_vcf/4139_NA_LIB2652_M__S48_TNscope.vcf -genome hg38 -sex ? -args.setPriorVcf 6 -args.setMappingBiasVcf ../n_out/mapping_bias_agilent_v6_hg38.rds -args.filterIntervals 100,0.05 -args.segmentation 0.005,NULL, -sampleid 4139_NA_LIB2652_M__S48 -min.ploidy 1.4 -max.ploidy 6 -max.non.clonal 0.2 -max.homozygous.loss 0.05,1e+07 -log.ratio.calibration 0.1 -model.homozygous FALSE -error 0.001 -interval.file ../ref_file/baits_hg38_intervals.txt -min.logr.sdev 0.15 -max.segments 300 -plot.cnv TRUE -vcf.field.prefix PureCN. -cosmic.vcf.file -DB.info.flag DB -POPAF.info.field POP_AF -Cosmic.CNT.info.field Cosmic.CNT -model beta -post.optimize FALSE -BPPARAM -log.file ../out_data//4139_NA_LIB2652_M__S48.log -normal.coverage.file -normalDB -args.filterVcf -fun.segmentation -test.num.copy -test.purity -speedup.heuristics
INFO [2024-03-08 13:27:10] Loading coverage files...
INFO [2024-03-08 13:27:11] Mean target coverages: 580X (tumor) 596X (normal).
WARN [2024-03-08 13:27:12] Allosome coverage missing, cannot determine sex.
WARN [2024-03-08 13:27:12] Allosome coverage missing, cannot determine sex.
INFO [2024-03-08 13:27:17] Removing 19604 intervals with missing log.ratio.
INFO [2024-03-08 13:27:17] Removing 49 low/high GC targets.
INFO [2024-03-08 13:27:17] Removing 27539 intervals excluded in normalDB.
INFO [2024-03-08 13:27:17] Removing 146 intervals with low total coverage in normal (< 150.00 reads).
INFO [2024-03-08 13:27:17] normalDB provided. Setting minimum coverage for segmentation to 0.0015X.
INFO [2024-03-08 13:27:17] Removing 2000 low count (< 100 total reads) intervals.
INFO [2024-03-08 13:27:17] Removing 621 low coverage (< 0.0015X) intervals.
INFO [2024-03-08 13:27:17] Using 21071 intervals (3178 on-target, 17893 off-target).
INFO [2024-03-08 13:27:17] Ratio of mean on-target vs. off-target read counts: 7.49
INFO [2024-03-08 13:27:17] Mean off-target bin size: 139312
INFO [2024-03-08 13:27:18] AT/GC dropout: 1.23 (tumor), 2.74 (normal), 38.59 (coverage log-ratio).
WARN [2024-03-08 13:27:18] High GC-bias in normalized tumor vs normal log2 ratio.
INFO [2024-03-08 13:27:18] Loading VCF...
INFO [2024-03-08 13:27:18] Found 9603 variants in VCF file.
INFO [2024-03-08 13:27:19] 3431 (35.7%) variants annotated as likely germline (DB INFO flag).
INFO [2024-03-08 13:27:19] 4139_NA_LIB2652_M__S48 is tumor in VCF file.
INFO [2024-03-08 13:27:19] 34 homozygous and 16 heterozygous variants on chrX.
INFO [2024-03-08 13:27:19] Sex from VCF: NA (Fisher's p-value: < 0.0001, odds-ratio: 3.77).
WARN [2024-03-08 13:27:19] Many variants removed by min.base.quality (20) filter. You might want to lower the cutoff.
INFO [2024-03-08 13:27:19] Removing 5155 low quality variants with non-offset BQ < 20.
INFO [2024-03-08 13:27:19] Base quality scores range from 19 to 49 (offset by 1)
INFO [2024-03-08 13:27:19] High median base quality score (49). UMI-barcoded data?
INFO [2024-03-08 13:27:20] Minimum number of supporting reads ranges from 1 to 41, depending on coverage and BQS.
INFO [2024-03-08 13:27:21] Initial testing for significant sample cross-contamination: unlikely
INFO [2024-03-08 13:27:21] Removing 1870 variants with AF < 0.030 or AF >= 0.970 or insufficient supporting reads or depth < 15.
INFO [2024-03-08 13:27:21] Total size of targeted genomic region: 0.39Mb (0.50Mb with 50bp padding).
INFO [2024-03-08 13:27:22] 9.9% of targets contain variants.
INFO [2024-03-08 13:27:22] Removing 2250 variants outside intervals.
INFO [2024-03-08 13:27:22] Setting somatic prior probabilities for dbSNP hits to 0.000500 or to 0.500000 otherwise.
INFO [2024-03-08 13:27:22] Loading mapping bias file mapping_bias_agilent_v6_hg38.rds...
INFO [2024-03-08 13:27:22] Found 37415 variants in mapping bias file.
INFO [2024-03-08 13:27:23] Imputing mapping bias for 86 variants...
INFO [2024-03-08 13:27:24] Excluding 126 novel or poor quality variants from segmentation.
INFO [2024-03-08 13:27:24] Sample sex: ?
INFO [2024-03-08 13:27:24] Segmenting data...
INFO [2024-03-08 13:27:25] Interval weights found, will use weighted PSCBS.
INFO [2024-03-08 13:27:25] MAPD of 176 allelic fractions: 0.02 (0.02 adjusted).
INFO [2024-03-08 13:27:25] Setting undo.SD parameter to 0.750000.
INFO [2024-03-08 13:27:39] Setting prune.hclust.h parameter to 0.250000.
INFO [2024-03-08 13:27:39] Found 78 segments with median size of 21.28Mb.
INFO [2024-03-08 13:27:39] Using 328 variants.
INFO [2024-03-08 13:27:39] Mean standard deviation of log-ratios: 0.66 (MAPD: 0.29)
INFO [2024-03-08 13:27:39] Mean standard deviation of on-target log-ratios only: 0.71 (MAPD: 0.22)
INFO [2024-03-08 13:27:39] Mean standard deviation of off-target log-ratios only: 0.50 (MAPD: 0.30)
INFO [2024-03-08 13:27:39] 2D-grid search of purity and ploidy...
INFO [2024-03-08 13:28:01] Local optima: 0.19/2.4, 0.29/2.4, 0.15/2, 0.29/3, 0.23/2.1, 0.52/3.2,
0.55/4.4, 0.42/3.8, 0.88/5.8, 0.45/2.6, 0.27/1.8, 0.95/4, 0.92/3,
0.62/2.8, 0.27/2, 0.65/1.4, 0.45/1.6, 0.52/2, 0.85/2.1
INFO [2024-03-08 13:28:01] Testing local optimum 1/19 at purity 0.19 and total ploidy 2.40...
INFO [2024-03-08 13:28:02] Recalibrating log-ratios...
INFO [2024-03-08 13:28:02] Testing local optimum 1/19 at purity 0.19 and total ploidy 2.40...
INFO [2024-03-08 13:28:02] Recalibrating log-ratios...
INFO [2024-03-08 13:28:02] Testing local optimum 1/19 at purity 0.19 and total ploidy 2.40...
INFO [2024-03-08 13:28:03] Recalibrating log-ratios...
INFO [2024-03-08 13:28:03] Testing local optimum 1/19 at purity 0.19 and total ploidy 2.40...
INFO [2024-03-08 13:28:04] Testing local optimum 2/19 at purity 0.29 and total ploidy 2.40...
INFO [2024-03-08 13:28:04] Recalibrating log-ratios...
INFO [2024-03-08 13:28:04] Testing local optimum 2/19 at purity 0.29 and total ploidy 2.40...
INFO [2024-03-08 13:28:05] Recalibrating log-ratios...
INFO [2024-03-08 13:28:05] Testing local optimum 2/19 at purity 0.29 and total ploidy 2.40...
INFO [2024-03-08 13:28:06] Recalibrating log-ratios...
INFO [2024-03-08 13:28:06] Testing local optimum 2/19 at purity 0.29 and total ploidy 2.40...
INFO [2024-03-08 13:28:07] Testing local optimum 3/19 at purity 0.15 and total ploidy 2.00...
INFO [2024-03-08 13:28:07] Recalibrating log-ratios...
INFO [2024-03-08 13:28:07] Testing local optimum 3/19 at purity 0.15 and total ploidy 2.00...
INFO [2024-03-08 13:28:08] Recalibrating log-ratios...
INFO [2024-03-08 13:28:08] Testing local optimum 3/19 at purity 0.15 and total ploidy 2.00...
INFO [2024-03-08 13:28:09] Recalibrating log-ratios...
INFO [2024-03-08 13:28:09] Testing local optimum 3/19 at purity 0.15 and total ploidy 2.00...
INFO [2024-03-08 13:28:09] Testing local optimum 4/19 at purity 0.29 and total ploidy 3.00...
INFO [2024-03-08 13:28:10] Recalibrating log-ratios...
INFO [2024-03-08 13:28:10] Testing local optimum 4/19 at purity 0.29 and total ploidy 3.00...
INFO [2024-03-08 13:28:11] Recalibrating log-ratios...
INFO [2024-03-08 13:28:11] Testing local optimum 4/19 at purity 0.29 and total ploidy 3.00...
INFO [2024-03-08 13:28:11] Recalibrating log-ratios...
INFO [2024-03-08 13:28:11] Testing local optimum 4/19 at purity 0.29 and total ploidy 3.00...
INFO [2024-03-08 13:28:12] Testing local optimum 5/19 at purity 0.23 and total ploidy 2.10...
INFO [2024-03-08 13:28:13] Recalibrating log-ratios...
INFO [2024-03-08 13:28:13] Testing local optimum 5/19 at purity 0.23 and total ploidy 2.10...
INFO [2024-03-08 13:28:14] Recalibrating log-ratios...
INFO [2024-03-08 13:28:14] Testing local optimum 5/19 at purity 0.23 and total ploidy 2.10...
INFO [2024-03-08 13:28:14] Recalibrating log-ratios...
INFO [2024-03-08 13:28:14] Testing local optimum 5/19 at purity 0.23 and total ploidy 2.10...
INFO [2024-03-08 13:28:15] Testing local optimum 6/19 at purity 0.52 and total ploidy 3.20...
INFO [2024-03-08 13:28:16] Recalibrating log-ratios...
INFO [2024-03-08 13:28:16] Testing local optimum 6/19 at purity 0.52 and total ploidy 3.20...
INFO [2024-03-08 13:28:16] Recalibrating log-ratios...
INFO [2024-03-08 13:28:16] Testing local optimum 6/19 at purity 0.52 and total ploidy 3.20...
INFO [2024-03-08 13:28:17] Recalibrating log-ratios...
INFO [2024-03-08 13:28:17] Testing local optimum 6/19 at purity 0.52 and total ploidy 3.20...
INFO [2024-03-08 13:28:18] Testing local optimum 7/19 at purity 0.55 and total ploidy 4.40...
INFO [2024-03-08 13:28:20] Recalibrating log-ratios...
INFO [2024-03-08 13:28:20] Testing local optimum 7/19 at purity 0.55 and total ploidy 4.40...
INFO [2024-03-08 13:28:20] Recalibrating log-ratios...
INFO [2024-03-08 13:28:20] Testing local optimum 7/19 at purity 0.55 and total ploidy 4.40...
INFO [2024-03-08 13:28:21] Recalibrating log-ratios...
INFO [2024-03-08 13:28:21] Testing local optimum 7/19 at purity 0.55 and total ploidy 4.40...
INFO [2024-03-08 13:28:22] Testing local optimum 8/19 at purity 0.42 and total ploidy 3.80...
INFO [2024-03-08 13:28:23] Recalibrating log-ratios...
INFO [2024-03-08 13:28:23] Testing local optimum 8/19 at purity 0.42 and total ploidy 3.80...
INFO [2024-03-08 13:28:23] Recalibrating log-ratios...
INFO [2024-03-08 13:28:23] Testing local optimum 8/19 at purity 0.42 and total ploidy 3.80...
INFO [2024-03-08 13:28:24] Recalibrating log-ratios...
INFO [2024-03-08 13:28:24] Testing local optimum 8/19 at purity 0.42 and total ploidy 3.80...
INFO [2024-03-08 13:28:25] Testing local optimum 9/19 at purity 0.88 and total ploidy 5.80...
INFO [2024-03-08 13:28:26] Recalibrating log-ratios...
INFO [2024-03-08 13:28:26] Testing local optimum 9/19 at purity 0.88 and total ploidy 5.80...
INFO [2024-03-08 13:28:26] Recalibrating log-ratios...
INFO [2024-03-08 13:28:26] Testing local optimum 9/19 at purity 0.88 and total ploidy 5.80...
INFO [2024-03-08 13:28:27] Recalibrating log-ratios...
INFO [2024-03-08 13:28:27] Testing local optimum 9/19 at purity 0.88 and total ploidy 5.80...
INFO [2024-03-08 13:28:28] Testing local optimum 10/19 at purity 0.45 and total ploidy 2.60...
INFO [2024-03-08 13:28:28] Recalibrating log-ratios...
INFO [2024-03-08 13:28:28] Testing local optimum 10/19 at purity 0.45 and total ploidy 2.60...
INFO [2024-03-08 13:28:29] Recalibrating log-ratios...
INFO [2024-03-08 13:28:29] Testing local optimum 10/19 at purity 0.45 and total ploidy 2.60...
INFO [2024-03-08 13:28:30] Recalibrating log-ratios...
INFO [2024-03-08 13:28:30] Testing local optimum 10/19 at purity 0.45 and total ploidy 2.60...
INFO [2024-03-08 13:28:30] Testing local optimum 11/19 at purity 0.27 and total ploidy 1.80...
INFO [2024-03-08 13:28:31] Recalibrating log-ratios...
INFO [2024-03-08 13:28:31] Testing local optimum 11/19 at purity 0.27 and total ploidy 1.80...
INFO [2024-03-08 13:28:32] Recalibrating log-ratios...
INFO [2024-03-08 13:28:32] Testing local optimum 11/19 at purity 0.27 and total ploidy 1.80...
INFO [2024-03-08 13:28:32] Recalibrating log-ratios...
INFO [2024-03-08 13:28:32] Testing local optimum 11/19 at purity 0.27 and total ploidy 1.80...
INFO [2024-03-08 13:28:33] Testing local optimum 12/19 at purity 0.95 and total ploidy 4.00...
INFO [2024-03-08 13:28:34] Recalibrating log-ratios...
INFO [2024-03-08 13:28:34] Testing local optimum 12/19 at purity 0.95 and total ploidy 4.00...
INFO [2024-03-08 13:28:34] Recalibrating log-ratios...
INFO [2024-03-08 13:28:34] Testing local optimum 12/19 at purity 0.95 and total ploidy 4.00...
INFO [2024-03-08 13:28:35] Recalibrating log-ratios...
INFO [2024-03-08 13:28:35] Testing local optimum 12/19 at purity 0.95 and total ploidy 4.00...
INFO [2024-03-08 13:28:35] Testing local optimum 13/19 at purity 0.92 and total ploidy 3.00...
INFO [2024-03-08 13:28:36] Recalibrating log-ratios...
INFO [2024-03-08 13:28:36] Testing local optimum 13/19 at purity 0.92 and total ploidy 3.00...
INFO [2024-03-08 13:28:37] Recalibrating log-ratios...
INFO [2024-03-08 13:28:37] Testing local optimum 13/19 at purity 0.92 and total ploidy 3.00...
INFO [2024-03-08 13:28:38] Recalibrating log-ratios...
INFO [2024-03-08 13:28:38] Testing local optimum 13/19 at purity 0.92 and total ploidy 3.00...
INFO [2024-03-08 13:28:38] Testing local optimum 14/19 at purity 0.62 and total ploidy 2.80...
INFO [2024-03-08 13:28:39] Recalibrating log-ratios...
INFO [2024-03-08 13:28:39] Testing local optimum 14/19 at purity 0.62 and total ploidy 2.80...
INFO [2024-03-08 13:28:40] Recalibrating log-ratios...
INFO [2024-03-08 13:28:40] Testing local optimum 14/19 at purity 0.62 and total ploidy 2.80...
INFO [2024-03-08 13:28:40] Recalibrating log-ratios...
INFO [2024-03-08 13:28:40] Testing local optimum 14/19 at purity 0.62 and total ploidy 2.80...
INFO [2024-03-08 13:28:41] Testing local optimum 15/19 at purity 0.27 and total ploidy 2.00...
INFO [2024-03-08 13:28:42] Recalibrating log-ratios...
INFO [2024-03-08 13:28:42] Testing local optimum 15/19 at purity 0.27 and total ploidy 2.00...
INFO [2024-03-08 13:28:42] Recalibrating log-ratios...
INFO [2024-03-08 13:28:42] Testing local optimum 15/19 at purity 0.27 and total ploidy 2.00...
INFO [2024-03-08 13:28:43] Recalibrating log-ratios...
INFO [2024-03-08 13:28:43] Testing local optimum 15/19 at purity 0.27 and total ploidy 2.00...
INFO [2024-03-08 13:28:44] Testing local optimum 16/19 at purity 0.65 and total ploidy 1.40...
INFO [2024-03-08 13:28:44] Recalibrating log-ratios...
INFO [2024-03-08 13:28:44] Testing local optimum 16/19 at purity 0.65 and total ploidy 1.40...
INFO [2024-03-08 13:28:45] Recalibrating log-ratios...
INFO [2024-03-08 13:28:45] Testing local optimum 16/19 at purity 0.65 and total ploidy 1.40...
INFO [2024-03-08 13:28:46] Recalibrating log-ratios...
INFO [2024-03-08 13:28:46] Testing local optimum 16/19 at purity 0.65 and total ploidy 1.40...
INFO [2024-03-08 13:28:47] Testing local optimum 17/19 at purity 0.45 and total ploidy 1.60...
INFO [2024-03-08 13:28:47] Recalibrating log-ratios...
INFO [2024-03-08 13:28:47] Testing local optimum 17/19 at purity 0.45 and total ploidy 1.60...
INFO [2024-03-08 13:28:48] Recalibrating log-ratios...
INFO [2024-03-08 13:28:48] Testing local optimum 17/19 at purity 0.45 and total ploidy 1.60...
INFO [2024-03-08 13:28:49] Recalibrating log-ratios...
INFO [2024-03-08 13:28:49] Testing local optimum 17/19 at purity 0.45 and total ploidy 1.60...
INFO [2024-03-08 13:28:50] Testing local optimum 18/19 at purity 0.52 and total ploidy 2.00...
INFO [2024-03-08 13:28:50] Recalibrating log-ratios...
INFO [2024-03-08 13:28:50] Testing local optimum 18/19 at purity 0.52 and total ploidy 2.00...
INFO [2024-03-08 13:28:51] Recalibrating log-ratios...
INFO [2024-03-08 13:28:51] Testing local optimum 18/19 at purity 0.52 and total ploidy 2.00...
INFO [2024-03-08 13:28:52] Recalibrating log-ratios...
INFO [2024-03-08 13:28:52] Testing local optimum 18/19 at purity 0.52 and total ploidy 2.00...
INFO [2024-03-08 13:28:53] Testing local optimum 19/19 at purity 0.85 and total ploidy 2.10...
INFO [2024-03-08 13:28:53] Recalibrating log-ratios...
INFO [2024-03-08 13:28:53] Testing local optimum 19/19 at purity 0.85 and total ploidy 2.10...
INFO [2024-03-08 13:28:54] Recalibrating log-ratios...
INFO [2024-03-08 13:28:54] Testing local optimum 19/19 at purity 0.85 and total ploidy 2.10...
INFO [2024-03-08 13:28:54] Recalibrating log-ratios...
INFO [2024-03-08 13:28:54] Testing local optimum 19/19 at purity 0.85 and total ploidy 2.10...
INFO [2024-03-08 13:28:55] Skipping 6 solutions that converged to the same optima.
INFO [2024-03-08 13:28:55] Skipping 13 solutions exceeding max.non.clonal (0.20): 0.68/76.38, 0.78/50.04, 0.15/101.42, 0.78/44.52, 0.95/35.97, 0.91/43.52, 0.95/29.28, 0.15/65.92, 0.95/25.36, 0.16/39.07, 0.15/48.83, 0.64/30.67, 0.95/17.1 (purity/tumor ploidy)
WARN [2024-03-08 13:28:55] Could not find valid purity and ploidy solution.
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