Long reads support for Sniffles files

[zhemingfan]

Overview

Currently, Sniffles (long read SV caller) outputs INVDUP SVTYPES which MAVIS does not handle. A temporary workaround of treating INVDUP as a combination of inversion, duplication, and insertion has been done.

A series of changes must be made to accommodate Sniffles:

• Add support for uncertain types (e.g DEL/INS)
• Add error handling of cases where breakpoints breakpoint start > breakpoint end
• Add unit tests that includes aforementioned cases (Exceptions include cases where PRECISE and IMPRECISE calls have pos=0) and cases where bp1 = 1 and bp2 = 0
• Add support for handling INVDUP from Sniffles input
• Ensure that errors in Sniffles calls addressed in this post are fixed

[creisle]

So it looks like the cause of the start > end error is the 0 position in the BND alt syntax. See example test to reproduce below

def test_convert_record():
    variant = VcfRecordType(
        9000,
        12000,
        'chr14_KI270722v1_random',
        alts=['N[chr17_GL000205v2_random:0['],
        ref='N',
        info=VcfInfoType(
            IMPRECISE=True,
            SVMETHOD="Snifflesv1.0.11",
            SVTYPE="BND",
            SUPTYPE="SR",
            SVLEN="0",
            STRANDS="+-",
            RE="5",
            REF_strand="0,0",
            AF="1",
        ),
    )
    records = convert_record(variant)
    records = [_convert_tool_row(r, SUPPORTED_TOOL.VCF, False) for r in records]

Based on the vcf 4.2 spec (https://samtools.github.io/hts-specs/VCFv4.2.pdf) these indicate connections to telomeres. I am not totally sure how to deal with these, but one solution might be to just make the 0 a 1 since we cannot start before the start of a sequence and coordinates are 1-based.

[zhemingfan]

Ensure that future versions use Sniffles2.0

[jessicadlang]

Hi, I'm trying to use a vcf produced by Sniffles2 with the convert feature, but am getting the following error:

Building DAG of jobs...
Using shell: /bin/bash
Provided cores: 1 (use --cores to define parallelism)
Rules claiming more threads will be scaled down.
Provided resources: mem_mb=16000, mem_mib=15259, disk_mb=1000, disk_mib=954, time_limit=57600, cpus=1
Select jobs to execute...

[Mon Dec 16 11:20:53 2024]
rule init_config:
input: /project/LangWorkspace/longread/PEO1/PEO1/output/config.raw.json
output: /project/LangWorkspace/longread/PEO1/PEO1/output/config.json
log: /project/LangWorkspace/longread/PEO1/PEO1/output/logs/init_config.snakemake.log.txt
jobid: 0
reason: Forced execution
resources: mem_mb=16000, mem_mib=15259, disk_mb=1000, disk_mib=954, tmpdir=/tmp, time_limit=57600, cpus=1, lo
g_dir=/project/LangWorkspace/longread/PEO1/PEO1/output/logs

mavis setup --config /project/LangWorkspace/longread/PEO1/PEO1/output/config.raw.json --outputfile /project/LangW
orkspace/longread/PEO1/PEO1/output/config.json
Activating singularity image /project8/LangWorkspace/mavis/.snakemake/singularity/692ac5546ddf42e31ddd9862317dc26b.simg
2024-12-16 11:20:58,207 [INFO] MAVIS: 3.1.2
2024-12-16 11:20:58,207 [INFO] hostname: slurm138.ssc.wisc.edu
2024-12-16 11:20:58,207 [INFO] arguments
2024-12-16 11:20:58,207 [INFO] command= 'setup'
2024-12-16 11:20:58,207 [INFO] config= '/project/LangWorkspace/longread/PEO1/PEO1/output/config.raw.json'
2024-12-16 11:20:58,207 [INFO] log= None
2024-12-16 11:20:58,207 [INFO] log_level= 'INFO'
2024-12-16 11:20:58,207 [INFO] outputfile= '/project/LangWorkspace/longread/PEO1/PEO1/output/config.json'
Traceback (most recent call last):
File "/usr/local/bin/mavis", line 8, in
sys.exit(main())
File "/usr/local/lib/python3.7/site-packages/mavis/main.py", line 295, in main
raise err
File "/usr/local/lib/python3.7/site-packages/mavis/main.py", line 272, in main
_config.add_bamstats_to_config(config)
File "/usr/local/lib/python3.7/site-packages/mavis/config.py", line 122, in add_bamstats_to_config
library.update(calculate_bam_stats(config, libname))
File "/usr/local/lib/python3.7/site-packages/mavis/config.py", line 46, in calculate_bam_stats
distribution_fraction=config['bam_stats.distribution_fraction'],
File "/usr/local/lib/python3.7/site-packages/mavis/bam/stats.py", line 275, in compute_genome_bam_stats
median = hist.median()
File "/usr/local/lib/python3.7/site-packages/mavis/bam/stats.py", line 77, in median
return (values[low_center - 1] + values[high_center - 1]) / 2
IndexError: list index out of range
[Mon Dec 16 11:21:30 2024]
Error in rule init_config:
jobid: 0
input: /project/LangWorkspace/longread/PEO1/PEO1/output/config.raw.json
output: /project/LangWorkspace/longread/PEO1/PEO1/output/config.json
log: /project/LangWorkspace/longread/PEO1/PEO1/output/logs/init_config.snakemake.log.txt (check log file(s) f
or error details)
shell:
mavis setup --config /project/LangWorkspace/longread/PEO1/PEO1/output/config.raw.json --outputfile /proje
ct/LangWorkspace/longread/PEO1/PEO1/output/config.json
(one of the commands exited with non-zero exit code; note that snakemake uses bash strict mode!)

Shutting down, this might take some time.
Exiting because a job execution failed. Look above for error message

Is this error because something in Sniffles2 output does not work with stats.py around line 77?

[jessicadlang]

I've been looking into the code more. Seems the problem is actually in generating the bam stats. Has there been any more thought to issue #210, which is related to long-read bams causing problems?