Workflow: Whole genome alignment and somatic variant detection

Fetched 2023-01-10 01:37:14 GMT
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workflow cluster_outputs Workflow Outputs cluster_inputs Workflow Inputs filter_docm_variants filter_docm_variants detect_variants Detect Variants workflow for WGS pipeline filter_docm_variants->detect_variants filter_docm_variants varscan_max_normal_freq varscan_max_normal_freq varscan_max_normal_freq->detect_variants varscan_max_normal_freq annotate_coding_only annotate_coding_only annotate_coding_only->detect_variants annotate_coding_only varscan_strand_filter varscan_strand_filter varscan_strand_filter->detect_variants varscan_strand_filter variants_to_table_genotype_fields variants_to_table_genotype_fields variants_to_table_genotype_fields->detect_variants variants_to_table_genotype_fields tumor_sample_name tumor_sample_name tumor_sample_name->detect_variants tumor_sample_name reference reference manta Set up and execute manta reference->manta reference concordance Concordance checking between Tumor and Normal BAM reference->concordance reference normal_bam_to_cram BAM to CRAM conversion reference->normal_bam_to_cram reference tumor_bam_to_cram BAM to CRAM conversion reference->tumor_bam_to_cram reference normal_alignment_and_qc wgs alignment with qc reference->normal_alignment_and_qc reference tumor_alignment_and_qc wgs alignment with qc reference->tumor_alignment_and_qc reference reference->detect_variants reference cnvkit cnvkit reference->cnvkit reference vep_ensembl_species vep_ensembl_species vep_ensembl_species->detect_variants vep_ensembl_species variants_to_table_fields variants_to_table_fields variants_to_table_fields->detect_variants variants_to_table_fields somalier_vcf somalier_vcf somalier_vcf->concordance vcf per_target_intervals per_target_intervals per_target_intervals->normal_alignment_and_qc per_target_intervals per_target_intervals->tumor_alignment_and_qc per_target_intervals varscan_p_value varscan_p_value varscan_p_value->detect_variants varscan_p_value tumor_name tumor_name tumor_name->tumor_alignment_and_qc sample_name summary_intervals summary_intervals summary_intervals->normal_alignment_and_qc summary_intervals summary_intervals->tumor_alignment_and_qc summary_intervals mutect_max_alt_alleles_in_normal_count mutect_max_alt_alleles_in_normal_count mutect_max_alt_alleles_in_normal_count->detect_variants mutect_max_alt_alleles_in_normal_count manta_non_wgs manta_non_wgs manta_non_wgs->manta non_wgs normal_sample_name normal_sample_name normal_sample_name->detect_variants normal_sample_name qc_minimum_mapping_quality qc_minimum_mapping_quality qc_minimum_mapping_quality->normal_alignment_and_qc minimum_mapping_quality qc_minimum_mapping_quality->tumor_alignment_and_qc minimum_mapping_quality bqsr_intervals bqsr_intervals bqsr_intervals->normal_alignment_and_qc bqsr_intervals bqsr_intervals->tumor_alignment_and_qc bqsr_intervals validated_variants validated_variants validated_variants->detect_variants validated_variants trimming trimming trimming->normal_alignment_and_qc trimming trimming->tumor_alignment_and_qc trimming vep_ensembl_version vep_ensembl_version vep_ensembl_version->detect_variants vep_ensembl_version vep_custom_annotations vep_custom_annotations vep_custom_annotations->detect_variants vep_custom_annotations normal_sequence normal_sequence: WT sequencing data and readgroup information normal_sequence->normal_alignment_and_qc sequence omni_vcf omni_vcf omni_vcf->normal_alignment_and_qc omni_vcf omni_vcf->tumor_alignment_and_qc omni_vcf cle_vcf_filter cle_vcf_filter cle_vcf_filter->detect_variants cle_vcf_filter mutect_max_alt_allele_in_normal_fraction mutect_max_alt_allele_in_normal_fraction mutect_max_alt_allele_in_normal_fraction->detect_variants mutect_max_alt_allele_in_normal_fraction manta_call_regions manta_call_regions qc_minimum_base_quality qc_minimum_base_quality qc_minimum_base_quality->normal_alignment_and_qc minimum_base_quality qc_minimum_base_quality->tumor_alignment_and_qc minimum_base_quality varscan_min_coverage varscan_min_coverage varscan_min_coverage->detect_variants varscan_min_coverage vep_to_table_fields vep_to_table_fields vep_to_table_fields->detect_variants vep_to_table_fields qc_intervals qc_intervals qc_intervals->normal_alignment_and_qc intervals qc_intervals->tumor_alignment_and_qc intervals scatter_count scatter_count scatter_count->detect_variants scatter_count vep_cache_dir vep_cache_dir vep_cache_dir->detect_variants vep_cache_dir strelka_cpu_reserved strelka_cpu_reserved strelka_cpu_reserved->detect_variants strelka_cpu_reserved bqsr_known_sites bqsr_known_sites bqsr_known_sites->normal_alignment_and_qc bqsr_known_sites bqsr_known_sites->tumor_alignment_and_qc bqsr_known_sites filter_somatic_llr_threshold filter_somatic_llr_threshold filter_somatic_llr_threshold->detect_variants filter_somatic_llr_threshold mutect_artifact_detection_mode mutect_artifact_detection_mode mutect_artifact_detection_mode->detect_variants mutect_artifact_detection_mode vep_pick vep_pick vep_pick->detect_variants vep_pick pindel_insert_size pindel_insert_size pindel_insert_size->detect_variants pindel_insert_size synonyms_file synonyms_file synonyms_file->detect_variants synonyms_file filter_somatic_llr_tumor_purity filter_somatic_llr_tumor_purity filter_somatic_llr_tumor_purity->detect_variants filter_somatic_llr_tumor_purity docm_vcf docm_vcf docm_vcf->detect_variants docm_vcf per_base_intervals per_base_intervals per_base_intervals->normal_alignment_and_qc per_base_intervals per_base_intervals->tumor_alignment_and_qc per_base_intervals manta_output_contigs manta_output_contigs manta_output_contigs->manta output_contigs cnvkit_target_average_size cnvkit_target_average_size cnvkit_target_average_size->cnvkit target_average_size tumor_sequence tumor_sequence: MT sequencing data and readgroup information tumor_sequence->tumor_alignment_and_qc sequence picard_metric_accumulation_level picard_metric_accumulation_level picard_metric_accumulation_level->normal_alignment_and_qc picard_metric_accumulation_level picard_metric_accumulation_level->tumor_alignment_and_qc picard_metric_accumulation_level normal_name normal_name normal_name->normal_alignment_and_qc sample_name target_intervals target_intervals target_intervals->detect_variants roi_intervals vep_ensembl_assembly vep_ensembl_assembly vep_ensembl_assembly->detect_variants vep_ensembl_assembly filter_somatic_llr_normal_contamination_rate filter_somatic_llr_normal_contamination_rate filter_somatic_llr_normal_contamination_rate->detect_variants filter_somatic_llr_normal_contamination_rate varscan_min_var_freq varscan_min_var_freq varscan_min_var_freq->detect_variants varscan_min_var_freq normal_insert_size_metrics normal_insert_size_metrics normal_gc_bias_metrics_chart normal_gc_bias_metrics_chart normal_summary_hs_metrics normal_summary_hs_metrics normal_flagstats normal_flagstats tumor_wgs_metrics tumor_wgs_metrics normal_verify_bam_id_metrics normal_verify_bam_id_metrics final_vcf final_vcf tumor_per_base_hs_metrics tumor_per_base_hs_metrics mutect_filtered_vcf mutect_filtered_vcf tumor_snv_bam_readcount_tsv tumor_snv_bam_readcount_tsv tumor_gc_bias_metrics tumor_gc_bias_metrics tumor_flagstats tumor_flagstats tumor_gc_bias_metrics_chart tumor_gc_bias_metrics_chart tumor_summary_hs_metrics tumor_summary_hs_metrics normal_per_target_hs_metrics normal_per_target_hs_metrics small_candidates small_candidates normal_insert_size_histogram normal_insert_size_histogram somalier_concordance_metrics somalier_concordance_metrics tumor_per_base_coverage_metrics tumor_per_base_coverage_metrics tumor_insert_size_histogram tumor_insert_size_histogram somatic_variants somatic_variants normal_gc_bias_metrics_summary normal_gc_bias_metrics_summary tumor_alignment_summary_metrics tumor_alignment_summary_metrics normal_alignment_summary_metrics normal_alignment_summary_metrics normal_gc_bias_metrics normal_gc_bias_metrics docm_filtered_vcf docm_filtered_vcf tumor_mark_duplicates_metrics tumor_mark_duplicates_metrics tumor_indel_bam_readcount_tsv tumor_indel_bam_readcount_tsv all_candidates all_candidates normal_per_base_hs_metrics normal_per_base_hs_metrics vep_summary vep_summary tumor_insert_size_metrics tumor_insert_size_metrics normal_mark_duplicates_metrics normal_mark_duplicates_metrics mutect_unfiltered_vcf mutect_unfiltered_vcf normal_indel_bam_readcount_tsv normal_indel_bam_readcount_tsv normal_cram normal_cram tumor_per_target_hs_metrics tumor_per_target_hs_metrics tumor_cram tumor_cram tumor_verify_bam_id_metrics tumor_verify_bam_id_metrics somalier_concordance_statistics somalier_concordance_statistics tumor_verify_bam_id_depth tumor_verify_bam_id_depth tumor_gc_bias_metrics_summary tumor_gc_bias_metrics_summary varscan_unfiltered_vcf varscan_unfiltered_vcf strelka_filtered_vcf strelka_filtered_vcf normal_per_target_coverage_metrics normal_per_target_coverage_metrics normal_snv_bam_readcount_tsv normal_snv_bam_readcount_tsv normal_per_base_coverage_metrics normal_per_base_coverage_metrics tumor_per_target_coverage_metrics tumor_per_target_coverage_metrics strelka_unfiltered_vcf strelka_unfiltered_vcf normal_wgs_metrics normal_wgs_metrics final_filtered_vcf final_filtered_vcf final_tsv final_tsv normal_verify_bam_id_depth normal_verify_bam_id_depth tumor_only_variants tumor_only_variants diploid_variants diploid_variants varscan_filtered_vcf varscan_filtered_vcf normal_index_cram samtools index cram normal_index_cram->normal_cram manta->small_candidates manta->somatic_variants manta->all_candidates manta->tumor_only_variants manta->diploid_variants concordance->somalier_concordance_metrics concordance->somalier_concordance_statistics normal_bam_to_cram->normal_index_cram cram tumor_index_cram samtools index cram tumor_bam_to_cram->tumor_index_cram cram tumor_index_cram->tumor_cram normal_alignment_and_qc->normal_insert_size_metrics normal_alignment_and_qc->normal_gc_bias_metrics_chart normal_alignment_and_qc->normal_summary_hs_metrics normal_alignment_and_qc->normal_flagstats normal_alignment_and_qc->normal_verify_bam_id_metrics normal_alignment_and_qc->normal_per_target_hs_metrics normal_alignment_and_qc->normal_insert_size_histogram normal_alignment_and_qc->normal_gc_bias_metrics_summary normal_alignment_and_qc->normal_alignment_summary_metrics normal_alignment_and_qc->normal_gc_bias_metrics normal_alignment_and_qc->normal_per_base_hs_metrics normal_alignment_and_qc->normal_mark_duplicates_metrics normal_alignment_and_qc->normal_per_target_coverage_metrics normal_alignment_and_qc->normal_per_base_coverage_metrics normal_alignment_and_qc->normal_wgs_metrics normal_alignment_and_qc->normal_verify_bam_id_depth normal_alignment_and_qc->manta normal_bam normal_alignment_and_qc->concordance bam_2 normal_alignment_and_qc->normal_bam_to_cram bam normal_alignment_and_qc->detect_variants normal_bam normal_alignment_and_qc->cnvkit reference tumor_alignment_and_qc->tumor_wgs_metrics tumor_alignment_and_qc->tumor_per_base_hs_metrics tumor_alignment_and_qc->tumor_gc_bias_metrics tumor_alignment_and_qc->tumor_flagstats tumor_alignment_and_qc->tumor_gc_bias_metrics_chart tumor_alignment_and_qc->tumor_summary_hs_metrics tumor_alignment_and_qc->tumor_per_base_coverage_metrics tumor_alignment_and_qc->tumor_insert_size_histogram tumor_alignment_and_qc->tumor_alignment_summary_metrics tumor_alignment_and_qc->tumor_mark_duplicates_metrics tumor_alignment_and_qc->tumor_insert_size_metrics tumor_alignment_and_qc->tumor_per_target_hs_metrics tumor_alignment_and_qc->tumor_verify_bam_id_metrics tumor_alignment_and_qc->tumor_verify_bam_id_depth tumor_alignment_and_qc->tumor_gc_bias_metrics_summary tumor_alignment_and_qc->tumor_per_target_coverage_metrics tumor_alignment_and_qc->manta tumor_bam tumor_alignment_and_qc->concordance bam_1 tumor_alignment_and_qc->tumor_bam_to_cram bam tumor_alignment_and_qc->detect_variants tumor_bam tumor_alignment_and_qc->cnvkit tumor_bam detect_variants->final_vcf detect_variants->mutect_filtered_vcf detect_variants->tumor_snv_bam_readcount_tsv detect_variants->docm_filtered_vcf detect_variants->tumor_indel_bam_readcount_tsv detect_variants->vep_summary detect_variants->mutect_unfiltered_vcf detect_variants->normal_indel_bam_readcount_tsv detect_variants->varscan_unfiltered_vcf detect_variants->strelka_filtered_vcf detect_variants->normal_snv_bam_readcount_tsv detect_variants->strelka_unfiltered_vcf detect_variants->final_filtered_vcf detect_variants->final_tsv detect_variants->varscan_filtered_vcf default1 false default1->detect_variants strelka_exome_mode default2 "wgs" default2->cnvkit method
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Inputs

ID Type Title Doc
docm_vcf File
omni_vcf File
trimming https://w3id.org/cwl/view/git/7638b3075863ae8172f4adaec82fb2eb8e80d3d5/definitions/types/trimming_options.yml#trimming_options (Optional)
vep_pick
reference String
tumor_name String (Optional)
normal_name String (Optional)
qc_intervals File
somalier_vcf File
manta_non_wgs Boolean (Optional)
scatter_count Integer

scatters each supported variant detector (varscan, pindel, mutect) into this many parallel jobs
synonyms_file File (Optional)
vep_cache_dir Directory
bqsr_intervals String[]
cle_vcf_filter Boolean
tumor_sequence https://w3id.org/cwl/view/git/7638b3075863ae8172f4adaec82fb2eb8e80d3d5/definitions/types/sequence_data.yml#sequence_data[] tumor_sequence: MT sequencing data and readgroup information

tumor_sequence represents the sequencing data for the MT sample as either FASTQs or BAMs with accompanying readgroup information. Note that in the @RG field ID and SM are required.

normal_sequence https://w3id.org/cwl/view/git/7638b3075863ae8172f4adaec82fb2eb8e80d3d5/definitions/types/sequence_data.yml#sequence_data[] normal_sequence: WT sequencing data and readgroup information

normal_sequence represents the sequencing data for the WT sample as either FASTQs or BAMs with accompanying readgroup information. Note that in the @RG field ID and SM are required.

varscan_p_value Float (Optional)
bqsr_known_sites File[]

One or more databases of known polymorphic sites used to exclude regions around known polymorphisms from analysis.
target_intervals File
summary_intervals https://w3id.org/cwl/view/git/7638b3075863ae8172f4adaec82fb2eb8e80d3d5/definitions/types/labelled_file.yml#labelled_file[]
tumor_sample_name String
manta_call_regions File (Optional)
normal_sample_name String
per_base_intervals https://w3id.org/cwl/view/git/7638b3075863ae8172f4adaec82fb2eb8e80d3d5/definitions/types/labelled_file.yml#labelled_file[]
pindel_insert_size Integer
validated_variants File (Optional)

An optional VCF with variants that will be flagged as 'VALIDATED' if found in this pipeline's main output VCF
vep_ensembl_species String

ensembl species - Must be present in the cache directory. Examples: homo_sapiens or mus_musculus
vep_ensembl_version String

ensembl version - Must be present in the cache directory. Example: 95
vep_to_table_fields String[]
annotate_coding_only Boolean (Optional)
filter_docm_variants Boolean (Optional)
manta_output_contigs Boolean (Optional)
per_target_intervals https://w3id.org/cwl/view/git/7638b3075863ae8172f4adaec82fb2eb8e80d3d5/definitions/types/labelled_file.yml#labelled_file[]
strelka_cpu_reserved Integer (Optional)
varscan_min_coverage Integer (Optional)
varscan_min_var_freq Float (Optional)
vep_ensembl_assembly String

genome assembly to use in vep. Examples: GRCh38 or GRCm38
varscan_strand_filter Integer (Optional)
vep_custom_annotations https://w3id.org/cwl/view/git/7638b3075863ae8172f4adaec82fb2eb8e80d3d5/definitions/types/vep_custom_annotation.yml#vep_custom_annotation[]

custom type, check types directory for input format
qc_minimum_base_quality Integer (Optional)
varscan_max_normal_freq Float (Optional)
variants_to_table_fields String[]
cnvkit_target_average_size Integer (Optional)

approximate size of split target bins for CNVkit; if not set a suitable window size will be set by CNVkit automatically
qc_minimum_mapping_quality Integer (Optional)
filter_somatic_llr_threshold Float

Sets the stringency (log-likelihood ratio) used to filter out non-somatic variants. Typical values are 10=high stringency, 5=normal, 3=low stringency. Low stringency may be desirable when read depths are low (as in WGS) or when tumor samples are impure.
mutect_artifact_detection_mode Boolean
filter_somatic_llr_tumor_purity Float

Sets the purity of the tumor used in the somatic llr filter, used to remove non-somatic variants. Probably only needs to be adjusted for low-purity (< 50%). Range is 0 to 1
picard_metric_accumulation_level String
variants_to_table_genotype_fields String[]
mutect_max_alt_alleles_in_normal_count Integer (Optional)
mutect_max_alt_allele_in_normal_fraction Float (Optional)
filter_somatic_llr_normal_contamination_rate Float

Sets the fraction of tumor present in the normal sample (range 0 to 1), used in the somatic llr filter. Useful for heavily contaminated adjacent normals. Range is 0 to 1

Steps

ID Runs Label Doc
manta
../tools/manta_somatic.cwl (CommandLineTool)
Set up and execute manta
cnvkit
../tools/cnvkit_batch.cwl (CommandLineTool)

Note: cnvkit batch is a complex command that is capable of running all or part of the cnvkit internal pipeline, depending on the combination of inputs provided to it. In order to take advantage of this, most inputs to this cwl are optional, so that different workflows can use different forms of the command while still using a single cwl file. For further reading, see the relevant cnvkit docs at https://cnvkit.readthedocs.io/en/stable/quickstart.html#build-a-reference-from-normal-samples-and-infer-tumor-copy-ratios https://cnvkit.readthedocs.io/en/stable/pipeline.html#batch In our pipelines, the command form is mainly determined by the components of the reference input. The somatic_exome cwl pipeline provides a fasta file and a normal bam, which causes the batch pipeline to construct a copy number reference (.cnn file) based on the normal bam. The germline_wgs cwl pipeline does not provide a normal bam; instead it passes a cnn reference file as an optional input. This file is intended to be manually generated from a reference normal sample for use in the pipeline. If it is not provided, cnvkit will automatically generate a flat reference file.

concordance
../tools/concordance.cwl (CommandLineTool)
Concordance checking between Tumor and Normal BAM
detect_variants Detect Variants workflow for WGS pipeline
tumor_index_cram
../tools/index_cram.cwl (CommandLineTool)
samtools index cram
normal_index_cram
../tools/index_cram.cwl (CommandLineTool)
samtools index cram
tumor_bam_to_cram
../tools/bam_to_cram.cwl (CommandLineTool)
BAM to CRAM conversion
normal_bam_to_cram
../tools/bam_to_cram.cwl (CommandLineTool)
BAM to CRAM conversion
tumor_alignment_and_qc
alignment_wgs.cwl (Workflow)
wgs alignment with qc
normal_alignment_and_qc
alignment_wgs.cwl (Workflow)
wgs alignment with qc

Outputs

ID Type Label Doc
final_tsv File
final_vcf File
tumor_cram File
normal_cram File
vep_summary File
all_candidates File
tumor_flagstats File
diploid_variants File (Optional)
normal_flagstats File
small_candidates File
somatic_variants File (Optional)
docm_filtered_vcf File
tumor_wgs_metrics File
final_filtered_vcf File
normal_wgs_metrics File
mutect_filtered_vcf File
tumor_only_variants File (Optional)
strelka_filtered_vcf File
varscan_filtered_vcf File
mutect_unfiltered_vcf File
tumor_gc_bias_metrics File
normal_gc_bias_metrics File
strelka_unfiltered_vcf File
varscan_unfiltered_vcf File
tumor_summary_hs_metrics File[]
normal_summary_hs_metrics File[]
tumor_insert_size_metrics File
tumor_per_base_hs_metrics File[]
tumor_verify_bam_id_depth File
normal_insert_size_metrics File
normal_per_base_hs_metrics File[]
normal_verify_bam_id_depth File
tumor_gc_bias_metrics_chart File
tumor_insert_size_histogram File
tumor_per_target_hs_metrics File[]
tumor_snv_bam_readcount_tsv File
tumor_verify_bam_id_metrics File
normal_gc_bias_metrics_chart File
normal_insert_size_histogram File
normal_per_target_hs_metrics File[]
normal_snv_bam_readcount_tsv File
normal_verify_bam_id_metrics File
somalier_concordance_metrics File
tumor_gc_bias_metrics_summary File
tumor_indel_bam_readcount_tsv File
tumor_mark_duplicates_metrics File
normal_gc_bias_metrics_summary File
normal_indel_bam_readcount_tsv File
normal_mark_duplicates_metrics File
somalier_concordance_statistics File
tumor_alignment_summary_metrics File
tumor_per_base_coverage_metrics File[]
normal_alignment_summary_metrics File
normal_per_base_coverage_metrics File[]
tumor_per_target_coverage_metrics File[]
normal_per_target_coverage_metrics File[]
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Permalink: https://w3id.org/cwl/view/git/7638b3075863ae8172f4adaec82fb2eb8e80d3d5/definitions/pipelines/somatic_wgs.cwl