CHANGELOG.md

nf-core/raredisease: Changelog

The format is based on Keep a Changelog and this project adheres to Semantic Versioning.

3.1.0 - Luigi [XXXX-XX-XX]

Added

• Update saltshaker classification reporting by adding customer ID to samples' reports and displaying them as tabs in html #856

Changed

• Replace ch_publish/subworkflow_results with named typed channel emits for qc_bam subworkflow #853
• Replace ch_publish/subworkflow_results with named typed channel emits for alignment and subsample-MT subworkflows #850

Fixed

• Fix intermittent CALL_SNV_DEEPVARIANT - wgs test failure caused by non-deterministic GLnexus quality scores by replacing variantsMD5 with vcf.summary #850

Parameters

Old parameter	New parameter

Tool updates

Tool	Old version	New version

3.0.0 - Mario [2026-05-12]

Added

• Interval parameter in the default retroseq call #717
• Tests for call_repeat_expansions and qc_bam subworkflows #713
• Feature to subsample mitochondrial alignments based on number of reads #748
• Functionality to generate coverage information using Sambamba depth #752
• Parameter to pass a file containing new sample ids to use with multiqc #764
• A helper function channelFromPath to create channels in a readable fashion in main.nf #766
• A helper function channelFromPathWithMeta to create channels in a readable fashion in main.nf #767
• A helper function channelFromSamplesheet to create channels in a readable fashion in main.nf #767
• A parameter homoplasmy_af_threshold to set genotypes of MT SNVs to 1/1 (homoplasmic) when AF >=homoplasmy_af_threshold #768
• Topic channels to local modules to caputure versions #774
• MitoSalt to detect mitochondrial deletions #743
• Tests for some of the subworkflows #780
• Tests for some of the subworkflows #782
• Tests for some of the subworkflows #783
• Test tags for dependent modules in subworkflow tests #800
• Stub test for scatter_genome subworkflow #802
• Add CAT_FASTQ before SEQTK_SAMPLE in call_sv_MT to merge reads across lanes before subsampling for MitoSalt #799
• Add new local SPLIT_CHR module to split reference FASTA by chromosome for CNVnator, and pass genome flag to all CNVnator steps #799
• Add peddy --sites hg38 argument when running with GRCh38 #799
• Saltshaker for downstream processing of mitochondrial SV calls from MitoSAlt #775
• Env variable NXF_SINGULARITY_NEW_PID_NAMESPACE = false to accommodate hisat2 running with latest Nextflow and Singularity #775
• Parameter exclude_alt to filter alignments to alt/unplaced contigs after alignment using samtools view, retaining only primary chromosomes (GRCh37: 1-22,X,Y,MT / GRCh38: chr1-chr22,chrX,chrY,chrM). Note that enabling this will restrict variant calling to these chromosomes #803
• Parameters save_all_mapped_as_cram and save_noalt_mapped_as_cram to replace save_mapped_as_cram, allowing independent control over publishing unfiltered and alt-filtered alignment files as CRAM #807
• Parameter run_vcfanno_db_sanity_check to check vcfanno database files for zero records and remove the corresponding annotation blocks from the TOML config before running vcfanno #821
• Added --skip_split_multiallelics parameter to allow users to skip the bcftools norm --multiallelics -both step in SNV calling (DeepVariant and Sentieon), which can cause indel quality degradation in single-interval runs #823
• Add find/concatenate step to concatenate saltshaker classification files before creating the html report, so the final report is case-level. #826
• Extended vcfanno database sanity check to include extra vcfanno resources (vcfanno_extra) alongside the main resources, and moved the check upstream to raredisease.nf so it covers both genome and mitochondrial SNV annotation subworkflows #834

Changed

• Use distinct output filenames for bcfools (in call_mobile_elements subworkflow) and svdb (in call_sv_tiddit subworkflow) #716
• Use nf-core's most severe consequence & pli scripts instead of local ones #732
• Use nf-core's VCF_FILTER_BCFTOOLS_ENSEMBLVEP subworkflow to generate clinical set instead of a local subworkflow #727
• Don't call mobile elements in mitochondrial DNA. #741
• Call SVs in mitochondria using mitochondrial alignments in the genome alignment files instead of from BAM files generated by the mitochondrial subworkflow. #742
• Update gens-preproc script #747
• Removed parameter bwa_as_fallback #763
• Sambamba depth now filters on not duplicates and not failed_quality_control #768
• Removed eKLIPse #743
• Removed haplocheck #778
• Removed HmtNote #779
• Updated svbd module #781
• Migrate file publishing from publishDir to a centralized output {} block for some workflows #784
• Replace local gens module with nf-core module #785
• Migrate file publishing from publishDir to a centralized output {} block for some workflows #787
• Migrate file publishing from publishDir to a centralized output {} block for some workflows #788
• Migrate file publishing from publishDir to a centralized output {} block for some workflows #789
• Remove redundant TABIX processes, and update configs for nf-test #790
• Migrate file publishing from publishDir to a centralized output {} block for some workflows #791
• Remove redundant ZIP_TABIX steps after VCFANNO in annotate_genome_snvs and annotate_mt_snvs by using VCFANNO's direct tbi output #799
• Collect genome fasta/fai channel in call_sv_tiddit to prevent per-sample re-emission #799
• Update cadd_resources channel to use channelFromPathWithMeta and set channelFromSamplesheet calls for svdb/ME resources as non-mandatory #799
• Run MitoSAlt.pl from bin rather than within container #775
• Include mitochonrdial SV calls in combined SV vcf, change call_sv output directory structure to remove mitochondria/ and genome/ #775
• Remove Qualimap and Haplogrep3 as they were made redundant by Picard and VerifyBamID2 #801
• Remove env variable NXF_SINGULARITY_NEW_PID_NAMESPACE from the config since this has to be set outside the subworkflow #804
• Run UPD_SITES, UPD_REGIONS, and CHROMOGRAPH for UPD only when analysis type is WGS #806
• Change saltshaker classification output from txt to html #808
• Sort parameters of CALL_STRUCTURAL_VARIANTS and CALL_SV_MANTA alphabetically #821

Fixed

• Fixed argument order of ch_genome_fai and ch_genome_fasta in the CALL_SNV_SENTIEON subworkflow #811
• Ensure deterministic sample ordering in Manta SV output by sorting BAM/BAI channel inputs #815
• Fixed inconsistencies in JSON schema #714
• Fixed conda declaration in the add_varcallername_to_bed module #733
• Fixed CADD annotation to support chr prefix #745
• Fixed mismatch between VCF and ROH calls when analysing multiple samples #755
• Fixed pipeline to run variant calling even with bait_padding set to 0 #757
• Fixed mitosalt channel handling so it runs on all samples in a trio #826
• Fixed runtime errors in call_sv_MT and call_structural_variants when MitoSAlt produces no structural variant calls #837
• Fixed vcfanno sanity check map closure to handle ch_vcfanno_resources emitting a list of paths #837
• Fixed PREP_MITOSALT msconfig output being consumed as a queue channel by converting it to a value channel with .collect() before passing to MITOSALT #837

Parameters

Old parameter	New parameter
	sambamba_regions
bwa_as_fallback
	multiqc_samples
	homoplasmy_af_threshold
	exclude_alt
save_mapped_as_cram
	save_all_mapped_as_cram
	save_noalt_mapped_as_cram
	run_vcfanno_db_sanity_check
	skip_split_multiallelics

Tool updates

Tool	Old version	New version
bcftools	1.20	1.21
bwa	0.7.18	0.7.19
deepvariant	1.8.0	1.9.0
eKLIPse	1.8
ensemblvep/vep	110	110.1
ensemblvep/filtervep	113	115.2
fastp	0.23.4	1.0.1
gatk4	4.5.0.0	4.6.2.0
gawk	5.3.0	5.3.1
genmod	3.9	3.10.2
gens-preproc	1.0.11
gens/preparecovandbaf		1.1.5
haplocheck	1.3.3
haplogrep3	3.2.2
hmtnote	0.7.2
htslib	1.20	1.21
MitoSalt		1.1.1
mosdepth	0.3.8	0.3.11
multiqc	1.32	1.33
ngsbits	202411	202512
picard	3.3.0	3.4.0
pigz	2.3.4	2.8
qualimap	2.3
sambamba		1.0.1
samtools	1.21	1.22.1
sentieon	202503	202503.02
stranger	0.9.4	0.10.0
svdb	2.8.3	2.8.4
tiddit	3.6.1	3.9.5
ucsc	447	482
vcfanno	0.3.5	0.3.7
vcf2cytosure	0.9.1	0.9.3

2.6.0 - Cacofonix [2025-06-25]

Added

• A feature to start the workflow from duplicate-marked bam files #682
• A functionality to take spring files as input #678

Changed

• Refactored code to only handle clinical variants in the generate_clinical_set workflow #693
• Refactored schema_input.json and nextflow_schema.json to improve the error messages and validations of the pipeline #692
• Updated add_most_severe_consequence and add_most_severe_pli to fix spelling and language server warnings #689
• Refactored code to address issues highlighted by language server #688
• Changed for loop to each in create_pedigree_file #683
• Refactored repeat annotation and updated Stranger #702

Fixed

• Errors due to channel name and structure inconsistencies in the sentieon SNV calling subworkflow#688

Parameters

Old parameter	New parameter
skip_haplogrep3	skip_tools
skip_fastp
skip_gens
skip_germlinecnvcaller
skip_peddy
skip_smncopynumbercaller
skip_vcf2cytosure
skip_me_calling	skip_subworkflows
skip_me_annotation
skip_mt_annotation
skip_mt_subsample
skip_repeat_annotation
skip_repeat_calling
skip_snv_annotation
skip_snv_calling
skip_sv_annotation
skip_sv_calling

Tool updates

Tool	Old version	New version
DeepVariant	1.6.1	1.8.0
add_most_severe_consequence	1.0	1.1
add_most_severe_pli	1.0	1.1
stranger	0.9.2	0.9.4

v2.5.0 - Fulliautomatix [2025-05-22]

Added

• A new parameter concatenate_snv_calls to generate a concatenated VCF file containing unannotated nuclear & mitochondrial SNV calls #699
• Functionality to check contamination in samples using VerifyBamID2 #701
• New parameters verifybamid_svd_bed, verifybamid_svd_mu, and verifybamid_svd_ud to supply reference files for VerifyBamID2 #701

Changed

• Default to remove mitochondrial variants with FILTER status not equal to PASS #697

Fixed

• Sort the input files before vcf2cytosure is invoked #697
• Use '--mitochondria-mode' by default when running Gatk4 FilterMutectCalls on mitochondrial variants#697

Parameters

Old parameter	New parameter
	concatenate_snv_calls
	verifybamid_svd_bed
	verifybamid_svd_mu
	verifybamid_svd_ud

Tool updates

Tool	Old version	New version
VerifyBamID2		2.0.1

2.4.0 - Vitalstatistix [2025-02-24]

Added

• Add markduplicates metrics to multiqc #679

Changed

• Update SVDB/merge to fix language server problems #684

Fixed

Parameters

Old parameter	New parameter

Tool updates

Tool	Old version	New version

2.3.0 - Getafix [2025-02-13]

Added

• A new option skip_haplogrep3 to skip haplogrep3 #675
• A new analysis option mito to call and annotate only mitochondrial variants #608
• An option extract_alignments to restrict analysis to specific contigs #644
• Fastp and ngsbits output files as input of MultiQC #647.
• Haplocheck output file as input of MultiQC #662

Changed

• Only Structural variants that PASS the filter will be reported and annotated #673
• Update haplogrep to v3.2.2 #672
• d4 files are not generated by default anymore #648
• Suffix used to identify unique fastq pairs from "_T" to "_LNUMBER" #638
• Merge output from germlinecnvcaller #635
• Update tools #623
• Update output file name prefix for upd and chromograph to sample-based #620
• Update tools #619
• Report only variants above 5% heteroplasmy in the clinical vcf file for mitochondria #616

Fixed

• Download tests #667
• Restrict deepvariant analysis of WES samples to bait regions #633, #658
• bcftools annotate declaration in annotate CADD subworkflow #624
• Rhocallviz subworkflow will only be invocated once per sample #621
• Updated createCaseChannel function to include a check for maternal and paternal ids being set to a numeric 0 #643
• Fixed issue of parsing sample sex in the configs #659
• Fixed how meta.id was set for input files, giving the resulting files clearer filenames #661

Parameters

Old parameter	New parameter
	extract_alignments
	restrict_to_contigs
	skip_haplogrep3

Tool updates

Tool	Old version	New version
bcftools	1.18	1.20
ensemblvep	112	110
genmod	3.8.2	3.9
haplogrep	2.4.0	3.2.2
mosdepth	0.3.6	0.3.8
multiqc	1.21	1.26
picard	3.1.1	3.3.0
samtools	1.19.2	1.21
sentieon	202308.02	202308.03
stranger	0.8.1	0.9.2
svdb	2.8.1	2.8.2
tabix	1.19.1	1.20

2.2.0 - Dogmatix [2024-09-13]

Added

• A new parameter mt_aligner to control which aligner is used to align reads to mitochondria #600
• A new parameter par_bed to pass a PAR bed files to deepvariant #598
• A new functionality to pass gzipped resources to vcfanno_extra_resources #589
• A new parameter vcfanno_extra_resources to pass an extra resource to vcfanno #588
• A new parameter scatter_count to control how many interval files are created from a genome (used to parallelize annotations) #585
• Print warning messages if user intends to perform ranking when there are no affected samples #579
• Two new parameters skip_repeat_annotation and skip_repeat_calling to skip calling and annotation of repeat expansions #574
• A new parameter skip_smncopynumbercaller to skip smncopynumbercaller module #574
• A new parameter skip_sv_calling to skip sv calling workflow #572
• Two new parameters skip_snv_calling and skip_repeat_analysis to skip snv calling and repeat analysis respectively #571
• Two new parameters mbuffer_mem and samtools_sort_threads to control resources given to mbuffer and samtools sort in the bwameme module #570

Changed

• Update default vep container from v110-v112 #609
• Default index for vcfanno extra annotation files from tbi to csi #606
• Updated the model for Sentieon DNAScope to v1.1 #601
• bwameme can no longer be used to align mitochondrial reads #600
• Males' X and Y chromosomes will be treated as haploids during variant calling by deepvariant #598
• Acceptable type for lane field in the samplesheet from number to string #597
• Allow 0 as a valid value for sex in the samplesheet #595
• Updated deepvariant to version 1.6.1 #587
• Parallelized vcfanno #585
• Skip ROH calling with bcftools if there are no affected samples #579
• Refactored tool citation list #577
• Removed skip_repeat_analysis added in #571 #574
• Remove several skip parameters that had been included in the pipeline to avoid failed CI tests (see parameters table below) #574
• readcount_intervals parameter is now mandatory for running germlinecnvcaller. #570
• Turn off CNVnator, TIDDIT, SMNCopyNumberCaller, Gens, and Vcf2cytosure for targeted analysis #573

Fixed

• Issues that cropped up when aligner and mt_aligner were different #605
• Update docs to show 'vep_plugin_files' as a mandatory parameter for SNV annotation #594
• Error in SVDB merge when only a single SV caller is run #586
• Errors due to misplaced version statements #578
• Stub crashes due to peddy reported in #566 [#576](https://github.com/nf-core/raredisease/pull/576]
• Docker manifest error from gnu-wget container #570
• Citations for bwameme #563

Parameters

Old parameter	New parameter
	mbuffer_mem
	mt_aligner
	samtools_sort_threads
	skip_repeat_calling
	skip_snv_calling
	skip_sv_calling
skip_eklipse
skip_fastqc
skip_haplocheck
skip_qualimap
	skip_smncopynumbercaller
	skip_repeat_annotation
	scatter_count
	vcfanno_extra_resources

Tool updates

Tool	Old version	New version
Deepvariant	1.5.0	1.6.1
ensemblvep	110	112

2.1.0 - Obelix [2024-05-29]

Added

• A new aligner, bwameme #553
• A new parameter run_mt_for_wes to turn on mitochondrial analysis for targeted analysis #552
• A new parameter bwa_as_fallback to switch aligner to bwa in case bwamem2 fails #551
• A new parameter skip_me_calling to skip mobile element calling and the subsequent annotation of them #556

Changed

• Changed valid values for sex according to the PED file format #550
• Refactored config files #538
• Refactored mobile element annotation subworkflow files #538
• Refactored to remove "a process is defined more than once" warning #557
• Updated modules #558

Fixed

• Include multiallelic indel sites in CADD scoring jobs #545
• Fixed issues with samtools merge not being run on samples sequenced over multiple lanes #538
• Fixed join issues in the mobile element calling subworkflow which occured when mobile_element_references were not provided #556

Parameters

Old parameter	New parameter
	bwameme
	bwa_as_fallback
	run_mt_for_wes
	skip_me_calling

:::note Parameter has been updated if both old and new parameter information is present. Parameter has been added if just the new parameter information is present. Parameter has been removed if new parameter information isn't present. :::

Module updates

Tool	Old version	New version
bwa	0.7.17	0.7.18
CADD	1.6.1	1.6.post1
Sentieon	202308.01	202308.02
bwameme		1.0.6

:::note Version has been updated if both old and new version information is present. Version has been added if just the new version information is present. Version has been removed if new version information isn't present. :::

2.0.1 - Asterix (Patch) [2024-03-25]

Fixed

• Germlinecnvcaller subworkflow uses the output channel casecalls from germlinecnvcaller module instead of calls which was invalid. #535

2.0.0 - Asterix [2024-03-18]

Added

• Use nf-validation plugin for parameter and samplesheet validation #386
• A new parameter skip_vep_filter to skip filtering based on vep results #416
• A metromap representating the core parts of the pipeline #428
• Metromap and logos for light and dark theme #432
• New parameters to skip qualimap and eklipse (--skip_qualimap and --skip_eklipse) #436
• Fix "there is no process matching config selector warnings" #435
• New parameters to skip fastqc and haplocheck (--skip_fastqc and --skip_haplocheck) #438
• CNVnator for copy number variant calling #438
• A new parameter svdb_query_bedpedbs to provide bedpe files as databases for SVDB query #449
• ngsbits samplegender to check sex #453
• New workflow for generating cgh files from SV vcfs for interpretation in the CytosSure interpretation software. Turned off by default #456
• Fastp to do adapter trimming. It can be skipped using --skip_fastp #457
• New workflow for calling insertion of mobile elements #440
• GATK CNVCaller uses segments instead of intervals, filters out "reference" segments between the calls, and fixes a bug with how ch_readcount_intervals was handled #472
• bwa aligner #474
• Add FOUND_IN tag, which mentions the variant caller that found the mutation, in the INFO column of the vcf files #471
• A new parameter vep_plugin_files to supply files required by vep plugins #482
• New workflow for annotating mobile elements #483
• Added a functionality to subsample mitochondrial alignment, and a new parameter skip_mt_subsample to skip the subworkflow #508.
• Chromograph to plot coverage across chromosomes #507
• Added a new parameter vep_filters_scout_fmt to supply a bed-like file exported by scout to be used in filter_vep #511.
• Added two new parameters variant_consequences_snv and variant_consequences_sv to supply variant consequence files for annotating SNVs and SVs. #509

Changed

• Tiddit updated to v3.6.1 #385
• Installed the nf-core version of the sentieon/bwamemindex module #397
• Installed the nf-core version of the sentieon/bwamem module #398
• Installed the nf-core version of the sentieon/readwriter module #399
• Installed the nf-core version of the sentieon/datametrics module #400
• Installed the nf-core version of the sentieon/dedup module. The dedup module also contains a call to Sentieon's LocusCollector #401
• Removing Sentieon-based BQSR. Recent Illumina sequencers tend to provide well-calibrated BQs, so BQSR may not provide much benefit #402
• Installed the nf-core version of the sentieon/dnamodelapply module #403
• Installed the nf-core version of the sentieon/wgsmetricsalgo module #404
• Installed the nf-core version of the sentieon/dnascope module #406
• Breaks down mitochondrial analysis workflow into smaller subworkflows that are more modular #419
• Replaced the parameter skip_mt_analysis which was used to turn on/off the mitochondrial workflow #419
• Adds a new parameter skip_mt_annotation which can be used to turn on/off annotation and ranking for mitochondrial SNVs #419
• Changed the name of the parameter from skip_cnv_calling to skip_germlinecnvcaller #435
• Check SVDB query input files for existence and correct format #476
• Change hardcoded platform value to params.platform in align_MT.config #475
• The split into clincial and research VCFs is now done before ranking the varaints #485
• Installed the nf-core version of ensemblvep/vep module #482
• The filenames of the ranked output VCF files have been changed. See output.md for more information#485
• Patched cnvnator module so that the processes didn't have to rerun after a failed run #503.
• Added a local module to generate bed files with variant caller names #505.

Fixed

• Invalid GATK4 container which caused incorrect singularity downloads with nf-core download nf-core/modules #3668
• Make the default cram prefix same as markduplicates prefix #392
• Sort ranked SV vcf before indexing with tabix #393
• Make target bed file optional for WGS mode (Issue #375) #395
• Added constraints to block the pipeline from running CollectWgsMetrics on WES samples #396
• Updated modules from nf-core #412
• If present, remove duplicate entries in probands and upd_children in the meta. #420
• Fixes vep starting as many instances as the square of the number of scatters. #405
• Replaced the logic where we added an arbitrary substring to keep file names unique after alignment which we then removed using a split operator, with a simple copy operation. #425
• Preventing a crash of rhocall annotate in the case of running four individuals whereof two are affected.
• Fixed memory qualifier in gatk4 germlinecnvcaller and postprocessgermlinecnvcalls
• Fixed wrong process names when outputting versions in ALIGN_SENTIEON and CALL_SNV.
• Fixed gens subworkflow #515

Parameters

Old parameter	New parameter
	--cnvnator_binsize
	--gens_pon_female
	--gens_pon_male
	--min_trimmed_length
	--mobile_element_references
	--mobile_element_svdb_annotations
	--mt_subsample_rd
	--mt_subsample_seed
	--ngsbits_samplegender_method
	--rtg_truthvcfs
	--run_rtgvcfeval
	--sample_id_map
	--score_config_mt
	--sdf
--pcr_amplification	--sentieon_dnascope_pcr_indel_model
	--skip_eklipse
	--skip_fastqc
	--skip_fastp
	--skip_gens
	--skip_germlinecnvcaller
	--skip_haplocheck
	--skip_me_annotation
	--skip_mt_annotation
	--skip_mt_subsample
	--skip_peddy
	--skip_qualimap
	--skip_vcf2cytosure
	--skip_vep_filter
	--svdb_query_bedpedbs
	--variant_consequences_snv
	--variant_consequences_sv
	--vcf2cytosure_blacklist
	--vep_plugin_files
	--vep_filters_scout_fmt
--gens_pon
--gens_switch
--skip_cnv_calling
--skip_mt_analysis

:::note Parameter has been updated if both old and new parameter information is present. Parameter has been added if just the new parameter information is present. Parameter has been removed if new parameter information isn't present. :::

v1.1.1 - Abu (Patch) [2023-07-26]

Fixed

• Avoids errors thrown by bcftools concat due to sample names in input vcf files not being in same order #388

v1.1.0 - Abu [2023-07-21]

Added

• Add GATK's cnv calling pipeline #362
• GATK's ShiftFasta to generate all the files required for mitochondrial analysis #354
• Feature to calculate CADD scores for indels #325
• HmtNote to annotate mitochondria #355
• MT del script to detect mitochondrial deletions #349
• eKLIPse to identify large mitochondrial deletions #365
• UPD+Chromograph to identify and visualize UPD sites and regions in the chromosomes #364 and #366
• Added check for presence of case id for each sample in samplesheet #357

Fixed

• Avoiding publishing uncompressed VCF-file from HMTNOTE_ANNOTATE. (The corresponding compressed VCF-file still gets published.) #368

v1.0.0 - Aladdin [2023-06-01]

Initial release of nf-core/raredisease, created with the nf-core template.

Added

• FastQC read quality control
• Read mapping with BWAmem2/Sentieon
• Qualimap & Picard tools quality control metrics
• Call repeat expansions with ExpansionHunter and Stranger
• SNV calling with DeepVariant/Sentieon
• SV calling with Manta and TIDDIT
• SNV annotation with bcftools roh, vcfanno, and vep
• SV annotation with SVDB query and vep
• Separate workflow for analysing and annotating mitochondrial variants
• Call copy number variants in the SMN gene using SMNCopyNumberCaller