stranger 0.5.5

Annotate VCF files with str variants

Stranger

Annotates output files from ExpansionHunter with the pathologic implications of the repeat sizes.

Installation

git clone github.com/moonso/stranger
cd stranger
pip install --editable .

Usage

stranger --help
Usage: stranger [OPTIONS] VCF

  Annotate str variants with str status

Options:
  -f, --repeats-file PATH         Path to a file with repeat definitions. See
                                  README for explanation  [default: /Users/man
                                  smagnusson/Projects/stranger/stranger/resour
                                  ces/repeatexpansionsloci.tsv]
  --version
  --loglevel [DEBUG|INFO|WARNING|ERROR|CRITICAL]
                                  Set the level of log output.  [default:
                                  INFO]
  --help                          Show this message and exit.

Repeat definitions

The repeats are called with Expansion Hunter as mentioned earlier. Expansion Hunter will annotate the number of times that a repeat has been seen in the bam files of each individual and what repeat id the variant has. Stranger will annotate the level of pathogenecity for the repeat number. The intervals that comes with the package are manually collected from the literature since there is no source where this information can be collected. There is a repeat definitions file that comes with Stranger in stranger/resources/repeatexpansionsloci.tsv. This is a tsv formated file on the following format:

hgnc_id	hgnc_symbol	repid	ru	normal_max	pathologic_min	disease
10548	ATXN1	ATXN1	CAG	35	45	SCA1
10555	ATXN2	ATXN2	CAG	31	39	SCA2
7106	ATXN3	ATXN3	CAG	44	60	SCA3
1388	CACNA1A	CACNA1A	CAG	18	20	SCA6
10560	ATXN7	ATXN7	CAG	19	37	SCA7
10561	ATXN8OS	ATXN8OS	CAG	50	80	SCA8
10549	ATXN10	ATXN10	ATTCT	32	800	SCA10
9305	PPP2R2B	PPP2R2B	CAG	35	49	SCA12
11588	TBP	TBP	CAG	31	49	SCA17
3951	FXN	FXN	CAG	35	51	FRDA
4851	HTT	HTT	CCG	36	37	Huntington
3775	FMR1	FMR1	CGG	65	200	FragileX
3776	AFF2	AFF2	CCG	25	200	FRAXE
13164	CNBP	CNBP	CCTG	30	75	DM2
2933	DMPK	DMPK	CAG	37	50	DM1
3033	ATN1	ATN1	CAG	34	49	DRPLA
15911	NOP56	NOP56	GGCCTG	14	650	SCA36
28337	C9ORF72	C9ORF72	GGCCCC	25	40	FTDALS1
8565	PABPN1	PABPN1	GCG	6	10	OPMD
2482	CSTB	CSTB	CGCGGGGCGGGG	3	30	EPM1
1541	CBL	CBL	CGG	79	100	FRAX11B
14203	JPH3	JPH3	CTG	28	40	HDL2
644	AR	AR	CAG	35	38	SBMA

The file is structured like a SCOUT gene panel, with STR specific columns.

Column	Content
HGNC_ID	HGNC identifier for the repeat or most associated gene.
HGNC_SYMBOL	HGNC symbol for the repeat or most associated gene.
REPID	ExpansionHunter repeat ID.
RU	Basic repeat unit, as seen in ExpansionHunter. Unused.
Normal_Max	(#copies) Longest repeat expected for normal individual; higher are marked pre- or full-mutation
Pathologic_Min	(#copies) Shortest repeat expected for pathology. This and higher is annotated as full-mutation.
Disease	Associated disease.

As a default the file that follows the distribution is used but the users can create their own file. Header line(s) should be preceded with a #.