Sex check

The purpose of the Sex check query is identification of individuals with discordant biological sex assignment. This dialog checks whether the recorded biological sex and the inherent biological sex of study participants match.

Sex Check module in Sequence Miner

Example use case

The user has a cohort of 200 subjects and wishes to confirm designated gender for all.

Description of the algorithm

Two analyses are performed for each sample:

1. The first analysis determines the fraction ratio (F_ratio) of heterozygous SNP calls for selected PNs on the X-chromosome and on chromosome 20 (the autosomal reference) with a minimum depth of 10 reads and good call quality calls. Females (having two X-chromosomes) should have a large set of heterozygous calls and males (having a single X-chromosome) should have few heterozygous calls.

   Het_Fraction = het_calls / (het_calls + hom_calls)

   F_Ratio = absolute(Het_Fraction20 - Het_FractionX) / Het_Fraction20

2. The second analysis determines the coverage of SRY, a Y chromosome gene, and compares it to coverage of a reference autosomal segment. Males should exhibit relatively high coverage of SRY, while females should only have a background of poorly-mapped reads. Coverage per bp is calculated across the SRY gene (ChrY:2,654,895-2,655,740) and a reference autosomal locus, Chr20:1,000,000-2,000,000. Coverage data comes from the source/cov/segment_cov.gord file.

   Coverage across SRY / Coverage across the reference region on chromosome 20

Interpreting the output

The F_ratio reflects the fraction ratio of heterozygous calls on the X chromosome to a reference autosome, chromosome 20. Samples with an F_ratio greater than 0.25 are annotated as “male”; samples with an F_ratio lower than 0.25 are annotated as “female”.

The SRYcovratio is the coverage of the SRY gene divided by the coverage of a 1Mb region on chromosome 20. The threshold is set to 0.2. Samples with a SRYcovratio greater than the threshold are annotated as “male”; samples with a SRYcovratio lower than the threshold are annotated as “female”.

Column descriptions

Report output columns and descriptions

Group	Column	Description
Basic	Chrom	Chromosome
	PN	Subject ID
Other columns	bpStart
	bpStop
	F_ratio	(value between 0 and 1) Ratio of heterozygous SNPs on the X-chromosome compared to heterozygous SNPs on autosomal chromosomes, calculated by: (ratio of het on X chromosome - ratio of het on chr20) / (ratio of het on chr20)
	GENDER	(male/female) Sex of sample assigned by the system administrator at time of sample import
	SNPSEX	(male/female) Sex determined by F_ratio. The threshold is set to 0.25 such that samples with an F_ratio greater than the 0.25 threshold are annotated as “male”; samples with an F_ratio lower than the 0.25 threshold are annotated as “female”
	SRYcovratio	(value between 0 and 1) Coverage of the SRY gene divided by the coverage of a 1Mb region on chromosome 20
	SRYSEX	(male/female) Sex determined by the ratio of the SRY gene coverage versus the coverage of a portion of chromosome 20. The threshold is set to 0.2 such that samples with a SRYcovratio greater than the 0.2 threshold are annotated as “male”; samples with a SRYcovratio lower than the 0.2 threshold are annotated as “female”
	status	Result of the sex check: CONSISTENT - The originally assigned biological sex matches that determined by SRYSEX and SNPSEX Sex Incorrect - The biological sex determined by SRYSEX and SNPSEX is concordant but discordant with that of the original input. Flags samples where the user-assigned sex is incorrect UNKNOWN - The biological sex determined by SRYSEX or SNPSEX is discordant and only one of the SRYSEX- or SNPSEX-determined sexes matches with that of the original input; flags samples in which the true biological sex of the sample cannot be determined

Perspective views

Perspectives subtabs focus on subsets of the columns in the Default view.

Perspectives

Perspective	Description
Default view
Sex Incorrect