hydra-genetics v0.4.0

Release notes

For more details on features and bug fixes see further down.

Features

QCI

Added a vcf file were the AD field is adapted so that QCI will report correct allele frequencies.

Purecn

Purecn is now used to estimate purity as a complement to the pathology estimation. CNV and HRD is calculated and reported for both estimates.

CNV

• Added a rule that locks for and reports small deletions in the CNV-data for the 20 loh genes.
• The CNV-hmtl report is greatly imporved with new functionality.
• In the germline input file for CNV-calculations (except gatk_cnv) some regions have been removed as they showed noisy allele freuqencies in Normal samples. These regions include for eaxmple MUC6, HLA, and CYP2D6.
• Added gene annotation of CNV segments in vcf-files using bcftools.

VCF filters

• The artifact filter does not filter only on position. Instead it also takes into account the allefrequence of the called variant and compare this with the median and standard deviation of the sample. If the difference is more than X Stdev (X = 5) the variant is not filtered even if it is observed in the normal samples.
• Multi-allelic variants in GATK are now retained

TMB

Background for the sequencing run is no longer reported.

DNA fusions

Added genepartner ERG to the gene_fuse analysis.

Bugfixes

• The artifact filter now correctly filters positions with only homozygous normal variants in normal. Also corrected caluclulation of the nr of standard deviations from the median when median allele frequency is 0.
• EGFR exon skipping in RNA is now working

Performance

Increased memory to all multithreaded jobs, speeding up some jobs.

Hydra modules with releases

• prealignment: v1.0.0 (updated, file name change only)
• alignment: v0.3.1 (updated, prealignment compatible)
• snv_indels: v0.3.0 (updated, multi-allelic variants in mutect2 not filtered)
• annotation: v0.3.0 (updated, added feature, minor bugfix in artifact annotation)
• filtering: v0.1.0 (not updated)
• qc: v0.3.0 (updated, prealignment compatible)
• biomarker: v0.2.0 (updated, purecn support added)
• cnv_sv: v0.3.1 (updated, added purecn)

Detailed features

• adapt rules and report to new structure (6990d24)
• add gridlines to genome view (b9df3b5)
• add guides to chromosome view (06b8cbf)
• add metadata to report (198644c)
• add script for merging JSON files (4008cc8)
• added arguments and files from Erik (f52961c)
• added blacklist for bad VAF regions (27f4201)
• added blacklist to cnvkit_call and cnvkit_scatter (3003011)
• added header info in vcf warning of the AD change for QCI (771322e)
• added purecn reference generation (fe4ac35)
• added purecn tc estimation to results (4214001)
• added purecn to pipeline (80d3bf5)
• Added rule call_small_cnv_deletions calling smaller deletions in cnv data from GATK (0ac2f58)
• added rule to fix vcf AD values that is used in QCI to calculate AF (edb9769)
• added total supporting reads to fusion report (0f79608)
• changed to internal segmentation (00661ca)
• convert output from single caller to JSON (6d70961)
• create separate print layout (86da7d1)
• filtering of loh cnvs also using baf to keep copy neutral cnvs (d55e470)
• import function through the module (8af029d)
• indicate points outside zoom range (24745d7)
• more flexible layout (9cfb79d)
• remove high VAFs from cnvkit plots (558e55b)
• run purecn with GATK cnv (6470af4)
• scale y-axis to extent of data when zooming (39f81d3)
• show results from other callers on hover (73f7f88)
• update checksum files (e1cc4be)
• update soft filter to match hard filter (26dfb06)
• update the pipeline to latest hydra releases (b668a56)
• update version for cnv_sv module (6b52c27)
• updated tags (43daaae)
• use all loh genes (016978c)
• use best segmentation (purecn internal) (6096cdf)
• y-axis zoom control (450728e)

Detailed bug Fixes

• activate all resultfiles (7b5c082)
• add classes to axes and labels (ff63504)
• add missing function (7c43eb9)
• add missing function (bd0d30d)
• added bgzip (cd6bdf0)
• added cnvkit container for cnvkit_export_seg (15db054)
• added missing rna results output (d8acf2b)
• added tc-file function to input (9b92fc6)
• adjust margins (eddf35c)
• bug where 0 became NA in table (4d68c93)
• bugfix (0193695)
• bugfix in calculations of high averages (9e8d158)
• bugfixes (59323f9)
• changed SJ input file to exon skipping (69e7c4a)
• config: added db field info to purecn (3be01c4)
• corrected germline filter ([6b618c8](http...

hydra-genetics v0.3.0

##Features
#Automatic testing
Automatic testing and comparison of the result with the previous version is now implemented

#Bedfile
reference:
design_bed: updated
design_intevals: updated
bcftools_filter_include_region:
nocnv: removed
exon: updated
gene_fuse:
genes: updated
report_gene_fuse:
filter_fusions: new

#CNV
1p19q is reported if more than 30% of both chromosome arms are under 1.4 copies (configurable).
New html CNV report!

#VCF filters

#Result files configuration
New simplified file for specifying output files: config/output_list.json

#DNA fusions
Added genepartners. New gene file.
Report is configurable regarding read support limits.

#QC
Added contamination estimation

#HRD
New implementation of HRD: CNVkit + scarHRD using only backbone regions. Still under development!

##Bugfix
RNA pipeline is now generating fusioncatcher output.
RNA exonskipping is now working
RNA report with correted gene names

##Local git
It is now possible to use a local git

##Hydra modules with releases
prealignment: v0.5.0
alignment: v0.3.0
snv_indels: v0.3.0
annotation: v0.2.0
filtering: v0.1.0
qc: v0.2.0
biomarker: v0.1.0
cnv_sv: v0.2.0

##Containers
All containers are now availiable on hydra-genetics dockerhub
Common container updated to 0.1.9 (only added features)
Hydra-genetics updated to 0.15.0

Features

• add cnvkit html report to final output (4384b81)
• add GATK data to visualisation (4407006)
• add gene annotations (3f5986e)
• add gene label background (2352864)
• add report template to schema (5b46741)
• add resource to generate rules (9593690)
• add table to CNV report (87cabe3)
• add three fusion partners to gene_fuse (fb1f4af)
• add VAF to chromosome view (6a96631)
• add VAF to JSON (c0aa776)
• added contamination check to pipeline (aedb308)
• added fp filtering of one fusion gene (9322c6d)
• added gatk_cnv scarHRD score (f7df157)
• added merged mutect2 bam files and bai. Also put cnv output in one folder per sample. (1fab0b7)
• added scarhrd calculations (f729310)
• animate dataset transition (857feec)
• big data validation for develop and master (8829aa2)
• bump up cnv_sv version to v0.2.0 (6c58d5c)
• config: better ranges and coloring (c4fa71e)
• config: decreased limit for 1p19q (3ad9cde)
• config: even better ranges and coloring (f2abf75)
• d3.js visualisation of all chromosomes (7fef05f)
• enable exclusion of chromosomes (e2052b8)
• gene_fuse: gene_fuse fusion filtering is now configurable (6f7171a)
• genome view before chromosome view (e892aef)
• indicate selected chromosome (8d74eed)
• limit log ratio y-axis to [-2, 2] (c814fce)
• make gene annotations optional (5ff402c)
• manta: run targeted manta (d38d22e)
• multiqc: added contamination as custom data to qc-stats table (5c5f407)
• multiqc: added contamination to multiqc (4f7a5cc)
• navigate to chromosomal region from table (6e5bb5f)
• new cnv_sv realease (d7d1e83)
• new configs for running the pipeline with hg38 (d4c6fce)
• plot all VAF data in genome view (86e92ee)
• plot selected chromosome (7f6cff1)
• plot single chromosomes (9d59b84)
• rename files to better reflect functionality (2200805)
• rm inhouse HRD output (58c970b)
• rm scarHRD based on GATK_cnv (ed8d8ea)
• scarHRD + CNVkit only on cnv backbone (f1fa85c)
• schema: set which version of default container that must be used (633b98f)
• script: update and correct fusion filtering (e73dbee)
• set version for misc (2468043)
• update list of output files (f47375c)
• update test_input_ALL.tsv (2468043)
• update test_input_VAL2022.tsv (2468043)
• updated tag to cnv_sv release (46f037e)
• updated tools requirements. (2f0f629)
• use filtered CNV data (94a004d)
• use svdb vcfs for results table (fa121d6)
• write cnvkit data as json (009319e)
• zoom in chromosome view (a6e554c)

Bug Fixes

• add conda and container to copy rules ([21da2e1](https:/...

v0.2.3-validation

##Features
#Bedfile
qc: target parameters are now calculated only on the exons (+/- 20 bp padding)

#CNV
The report now also reports LoH genes if below 1.4 copies (can be configured). Currently defaults to only PTEN and CDKN2A but can be changed in config.
The report now includes both caller even if one of the caller reported a call below threshold.
1p19q is reported if more than 50% of both chromosome arms are under 1.4 copies (configurable).

#VCF filters
Germline variants are filtered out if over 0.5% in GnomAD. COSMIC rescue filter removed to reduce noise.

#Background
New background normal panel. Increased DP limit from 50 to 500 and decreased max AF from 5% to 1.5%. This decreases noise in the background panel due to low coverage positions and removes positions that are coverared by the artifact filter.

#DNA fusions
Added all fusion genes in the design. Added fusion gene partners from the RNA-panel. Fusion gene partners are needed for the program to call the fusion.
A fusion report is now generated which filters out noise and false positve results.

#QC
% target coverage over 500X is now also reported

#TMB
Updated slope to reflect changes in SNP-calling. Also decreased DP limit to 100 which has almost no effect on the TMB-value.

##Bugfix
RNA SNP_id calling is now working

##Hydra modules with releases (same as v0.2.0-alpha):
prealignment: v0.3.1
alignment: v0.2.0
snv_indels: v0.2.0

##Containers
All containers are now located on our own docker hub for better control

v0.2.2-alpha

##Features
#Bedfile
cnv backbone snps now have 100bp padding instead of 200bp
fusion regions are split into exons and introns (used for intron filtering)
exon_only bedfile: removed MUC6 exon 31 as it has so much noise in it

#CNV
Germline vcf-file for BAF-calculations in CNVkit now include only SNPs and must have AD > 50. This improves BAF noise levels significantly.
Germline vcf filters are now configured in the config in the same manner as fot other vcf filters.
Amplification CNVs passing filters now also reported in a text file (.cnv_report.tsv)

#VCF filters
"Uppsala filter"
Intron variants are filtered out based on VEP annotation if not annotated with splice information and not in MET or TERT.
Germline variants are filtered out if under 0.01% (before 1%) if not in Clinvar.

##Bugfix
#MultiQC
The multiQC report now accepts the multiqc config file and looks like it should
#Filters
Fixed error in filter so that COSMIC variants are retained

##Hydra modules with releases (same as v0.2.0-alpha):
prealignment: v0.3.1
alignemnt: v0.2.0
snv_indels: v0.2.0

##RNA
The RNA pipeline should now have approximately the same functionality as the old Twist-RNA pipeline but are still to be properly tested

#Fusion-callers:
*Arriba
*Star-Fusion
*Fusioncatcher

#Fusion report collecting fusion from the three callers using configurable read cutoffs

#Exon skipping:
*MET
*EGFR

#QC
*MultiQC
*Picard
*Samtools
*House keeping gene coverage
*ID SNPs

v0.2.0-alpha

New features:
Hard filtering of mutect2 variants with built in filtering (removes many false small INDELs)
Adding multiple variant codons after hardfiltering to avoid false positives
CNV filtering of genes with amplifications

Config:
MultiQC config has been updated
Filtering config has been updated

Bug fix:
Background annotation now also annotate positions with 0 median (removes low VAF fasle postives)

New normal background:
Added new background file for nextseq normals that excludes samples from Umeå as they had abnormally high background (caused some false negatives)

Filters:
Updated soft and hard filters in general and Uppsala specific filters.

Hydra modules with releases:
prealignment: v0.3.1
alignemnt: v0.2.0
snv_indels: v0.2.0

v0.1.6-alpha

Updated with:

• improved filtering
• new panel of normals
• svdb annotation
• cnvkit images on genome level

v0.1.5-alpha

Twist Solid DNA pipeline with filtering activated and hotspot coverage

v0.1.1-alpha

First alpha release of the Twist Solid pipeline based on hydra-genetics for the GMS560 panel.