Updated --help

[ACEnglish]

Hello,

I found the sniffles --help to be difficult to read. I've refactored it so that text is less wide and I've separated --help and --example (detailed below). This is technically a breaking change in that parameters which used the tobool as a type were all replaced with action="store_false". Therefore, any pipeline which has hard coded calls to e.g. sniffles --qc-stdev false would need to be updated to sniffles --qc-stdev

Note that the formatting in the below examples is a different from what would be seen in a terminal due to github applying formatting.

default `sniffles` output

usage: sniffles --input SORTED_INPUT.bam [--vcf OUTPUT.vcf] [--snf MERGEABLE_OUTPUT.snf] [--threads 4] [--mosaic]

Sniffles2: A fast structural variant (SV) caller for long-read sequencing data
Version 2.4
Contact: [email protected]

Use --help for full parameter information
Use --example for detailed usage information
sniffles: error: the following arguments are required: -i/--input

`sniffles --help` output

usage: sniffles --input SORTED_INPUT.bam [--vcf OUTPUT.vcf] [--snf MERGEABLE_OUTPUT.snf] [--threads 4] [--mosaic]
Sniffles2: A fast structural variant (SV) caller for long-read sequencing data

Version 2.4

Contact: [email protected]
Use --help for full parameter information

Use --example for detailed usage information
options:

-h, --help            show this help message and exit

--example             Show example usage and exit

--version             show program's version number and exit
Common parameters:

-i IN [IN ...], --input IN [IN ...]

For single-sample calling: A coordinate-sorted and indexed .bam/.cram

(BAM/CRAM format) file containing aligned reads. - OR - For multi-sample

calling: Multiple .snf files (generated before by running Sniffles2 for

individual samples with --snf)

-v OUT.vcf, --vcf OUT.vcf

VCF output filename to write the called and refined SVs to. If the given

filename ends with .gz, the VCF file will be automatically bgzipped and a

.tbi index built for it.

--snf OUT.snf         Sniffles2 file (.snf) output filename to store candidates for later multi-

sample calling

--reference REF.fa    (Optional) Reference sequence the reads were aligned against. To enable

output of deletion SV sequences, this parameter must be set.

--tandem-repeats IN.bed

(Optional) Input .bed file containing tandem repeat annotations for the

reference genome.

--regions REG.bed     (Optional) Only process the specified regions.

-c, --contig          (Optional) Only process the specified contigs. May be given more than once.

--phase               Determine phase for SV calls (requires the input alignments to be phased)

-t, --threads         Number of parallel threads to use (4)
SV Filtering parameters:

--minsupport          Min number of supporting reads for a SV to be reported (auto)

--minsupport-auto-mult

Coverage based auto-minsupport multiplier for germline mode (0.1/0.025)

--minsvlen            Min SV length in bp (50)

--minsvlen-screen-ratio

Min length for SV candidates as fraction of --minsvlen (0.9)

--mapq                Alignments with mapping quality lower than this value will be ignored

--no-qc, --qc-output-all

Output all SV candidates, disregarding quality control steps

--qc-stdev            Apply filtering based on SV start position and length standard deviation

--qc-stdev-abs-max    Max standard deviation for SV length and size in bp (500)

--qc-strand           Apply filtering based on strand support of SV calls

--qc-coverage         Min surrounding region coverage of SV calls (1)

--long-ins-length     Insertion SVs longer than this are subjected to more sensitive filtering

(2500)

--long-del-length     Deletion SVs longer than this are subjected to central coverage drop-based

filtering. Not applicable for --mosaic (50000)

--long-inv-length     Inversion SVs longer than this value are not subjected to central coverage

drop-based filtering (10000)

--long-del-coverage   Long deletions with central coverage higher than this value will be

filtered. Not applicable for --mosaic (0.66)

--long-dup-length     Duplication SVs longer than this value are subjected to central coverage

increase-based filtering. Not applicable for --mosaic (50000)

--qc-bnd-filter-strand

Filter breakends that do not have support for both strands

--bnd-min-split-length

Min length of read splits to be considered for breakends (1000)

--long-dup-coverage   Long duplications with central coverage lower than this value will be

filtered. Not applicable for --mosaic (1.33)

--max-splits-kb       Additional number of splits per kilobase read sequence allowed before reads

are ignored (0.1)

--max-splits-base N   Base number of splits allowed before reads are ignored (3)

--min-alignment-length

Reads with alignments shorter than this length in bp will be ignored

--phase-conflict-threshold

Max fraction of conflicting reads permitted for SV phase information to be

labelled as PASS. Only for --phase (0.1)

--detect-large-ins    Infer insertions that are longer than most reads and therefore are spanned

by few alignments only.
SV Clustering parameters:

--cluster-binsize     Initial screening bin size in bp (100)

--cluster-r           Multiplier for SV start position standard deviation criterion in cluster

merging (2.5)

--cluster-repeat-h    Multiplier for mean SV length criterion for tandem repeat cluster merging

(1.5)

--cluster-repeat-h-max

Max. merging distance based on SV length criterion for tandem repeat cluster

merging (1000)

--cluster-merge-pos   Max. merging distance for insertions and deletions on the same read and

cluster in non-repeat regions (150)

--cluster-merge-len   Max. size difference for merging SVs as fraction of SV length (0.33)

--cluster-merge-bnd   Max. merging distance for breakend SV candidates (1000)
SV Genotyping parameters:

--genotype-ploidy     Sample ploidy (2)

--genotype-error      Estimated false positive rate for leads (0.05)

--sample-id           Custom ID for this sample (SAMPLE))

--genotype-vcf IN.vcf

Forced calling input.vcf
Multi-Sample Calling / Combine parameters:

--combine-high-confidence

Min fraction of passed QC samples an SV needs (0.0)

--combine-low-confidence

Min fraction of present samples an SV needs (0.2)

--combine-low-confidence-abs

Min number of present samples an SV needs (2)

--combine-null-min-coverage

Min coverage for a genotype to be reported as 0/0 instead of ./. (5)

--combine-match       Multiplier for maximum deviation of multiple SV's start/end position for

them to be combined across samples. Given by

max_dev=M*sqrt(min(SV_length_a,SV_length_b)), where M is this parameter

(250)

--combine-match-max   Upper limit for the max deviation computed for --combine-match, in bp (1000)

--combine-separate-intra

Disable combination of SVs within the same sample

--combine-output-filtered

Include low-confidence / mosaic SVs in multi-calling

--combine-pair-relabel

Override low-quality genotypes when combining paired samples

--combine-pair-relabel-threshold

Genotype quality minimum before relabeling (20)

--combine-close-handles

Close .SNF file handles after each use to avoid opened files ulimit when

merging many samples.

--combine-pctseq      Min alignment distance as percent of SV length to be merged. 0=off (0.7)
Output formatting parameters:

--output-rnames       Output names supporting reads in INFO/RNAME

--no-consensus        Disable consensus sequence generation for insertion SV calls

--no-sort             Do not sort output VCF

--no-progress         Disable progress display

--quiet               Disable any non-error logging

--max-del-seq-len     Max deletion sequence length in output before writing as symbolic <DEL>

(50000)

--symbolic            Output all SVs as symbolic

--allow-overwrite     Allow overwriting existing output files
Mosaic/somatic calling mode parameters:

--mosaic              Turn on mosaic calling

--mosaic-af-max       Max allele frequency for which SVs are considered mosaic (0.2)

--mosaic-af-min       Min allele frequency for mosaic SVs to be output (0.05)

--mosaic-qc-invdup-min-length

Min SV length for mosaic inversion and duplication SVs (500)

--mosaic-qc-coverage-max-change-frac

Max relative coverage change across breakpoints (0.1)

--mosaic-qc-strand    Apply filtering based on strand support of calls

--mosaic-include-germline

Report germline SVs as well in mosaic mode
Developer parameters:

--combine-consensus   Output the consensus genotype of all samples

--qc-coverage-max-change-frac F

Max relative coverage change across SV breakpoints

`sniffles --example` output

sniffles example commands:
Call SVs for a single sample

-> sniffles --input sorted_indexed_alignments.bam --vcf output.vcf
... OR, with CRAM input and bgzipped+tabix indexed VCF output:

-> sniffles --input sample.cram --vcf output.vcf.gz
... OR, producing only a SNF file with SV candidates:

-> sniffles --input sample1.bam --snf sample1.snf
... OR, simultaneously produce a single-sample VCF and SNF file:

-> sniffles --input sample1.bam --vcf sample1.vcf.gz --snf sample1.snf
... OR, with tandem repeat annotations, reference (for DEL sequences) and mosaic mode for detecting rare SVs:

-> sniffles --input sample1.bam --vcf sample1.vcf.gz --tandem-repeats tandem_repeats.bed --reference genome.fa --mosaic
Multi-sample calling

Step 1. Create .snf for each sample:

-> sniffles --input sample1.bam --snf sample1.snf

Step 2. Combined calling:

-> sniffles --input sample1.snf sample2.snf ... sampleN.snf --vcf multisample.vcf
... OR, using a .tsv file containing a list of .snf files and sample ids (one sample per line):

Step 2. Combined calling:

-> sniffles --input snf_files_list.tsv --vcf multisample.vcf
Determine genotypes for a set of known SVs (force calling)

-> sniffles --input sample.bam --genotype-vcf input_known_svs.vcf --vcf output_genotypes.vcf