anomIdentifyLowQuality {GWASTools} | R Documentation

## Identify low quality samples

### Description

Identify low quality samples for which false positive rate for anomaly detection is likely to be high. Measures of noise (high variance) and high segmentation are used.

### Usage

    anomIdentifyLowQuality(snp.annot, med.sd, seg.info,
      sd.thresh, sng.seg.thresh, auto.seg.thresh)

### Arguments

`snp.annot` | `SnpAnnotationDataFrame` with column "eligible", where "eligible" is a logical vector indicating whether a SNP is eligible for consideration in anomaly detection (usually FALSE for HLA and XTR regions, failed SNPs, and intensity-only SNPs). See `HLA` and `pseudoautosomal`.
`med.sd` | data.frame of median standard deviation of BAlleleFrequency (BAF) or LogRRatio (LRR) values across autosomes for each scan, with columns "scanID" and "med.sd". Usually the result of `medianSdOverAutosomes`. Usually only eligible SNPs are used in these computations. In addition, for BAF, homozygous SNPS are excluded.
`seg.info` | data.frame with segmentation information from `anomDetectBAF` or `anomDetectLOH`. Columns must include "scanID", "chromosome", and "num.segs". (For `anomDetectBAF`, segmentation information is found in $seg.info from output. For `anomDetectLOH`, segmentation information is found in $base.info from output.)
`sd.thresh` | Threshold for `med.sd` above which scan is identified as low quality. Suggested values are 0.1 for BAF and 0.25 for LOH.
`sng.seg.thresh` | Threshold for segmentation factor for a given chromosome, above which the chromosome is said to be highly segmented. See Details. Suggested values are 0.0008 for BAF and 0.0048 for LOH.
`auto.seg.thresh` | Threshold for segmentation factor across autosome, above which the scan is said to be highly segmented. See Details. Suggested values are 0.0001 for BAF and 0.0006 for LOH.

### Details

Low quality samples are determined separately with regard to each of the two methods of segmentation, `anomDetectBAF` and `anomDetectLOH`. BAF anomalies (respectively LOH anomalies) found for samples identified as low quality for BAF (respectively LOH) tend to have a high false positive rate.

A scan is identified as low quality due to high variance (noise), i.e. if `med.sd` is above a certain threshold `sd.thresh`.

High segmentation is often an indication of artifactual patterns in the B Allele Frequency (BAF) or Log R Ratio values (LRR) that are not always captured by high variance. Here segmentation information is determined by `anomDetectBAF` or `anomDetectLOH` which use circular binary segmentation implemented by the R-package DNAcopy. The measure for high segmentation is a "segmentation factor" = (number of segments)/(number of eligible SNPS). A single chromosome segmentation factor uses information for one chromosome. A segmentation factor across autosomes uses the total number of segments and eligible SNPs across all autosomes. See `med.sd`, `sd.thresh`, `sng.seg.thresh`, and `auto.seg.thresh`.

### Value

A data.frame with the following columns:

`scanID` | integer id for the scan
`chrX.num.segs` | number of segments for chromosome X
`chrX.fac` | segmentation factor for chromosome X
`max.autosome` | autosome with highest single segmentation factor
`max.auto.fac` | segmentation factor for chromosome = `max.autosome`
`max.auto.num.segs` | number of segments for chromosome = `max.autosome`
`num.ch.segd` | number of chromosomes segmented, i.e. for which change points were found
`fac.all.auto` | segmentation factor across all autosomes
`med.sd` | median standard deviation of BAF (or LRR values) across autosomes. See `med.sd` in Arguments section.
`type` | one of the following, indicating reason for identification as low quality: `auto.seg`: segmentation factor `fac.all.auto` above `auto.seg.thresh` but `med.sd` acceptable `sd`: standard deviation factor `med.sd` above `sd.thresh` but `fac.all.auto` acceptable `both.sd.seg`: both high variance and high segmentation factors, `fac.all.auto` and `med.sd`, are above respective thresholds `sng.seg`: segmentation factor `max.auto.fac` is above `sng.seg.thresh` but other measures acceptable `sng.seg.X`: segmentation factor `chrX.fac` is above `sng.seg.thresh` but other measures acceptable

### Author(s)

Cecelia Laurie

### See Also

`findBAFvariance`, `anomDetectBAF`, `anomDetectLOH`

### Examples

    library(GWASdata)
    data(illuminaScanADF, illuminaSnpADF)

    blfile <- system.file("extdata", "illumina_bl.gds", package="GWASdata")
    bl <- GdsIntensityReader(blfile)
    blData <-  IntensityData(bl, scanAnnot=illuminaScanADF, snpAnnot=illuminaSnpADF)

    genofile <- system.file("extdata", "illumina_geno.gds", package="GWASdata")
    geno <- GdsGenotypeReader(genofile)
    genoData <-  GenotypeData(geno, scanAnnot=illuminaScanADF, snpAnnot=illuminaSnpADF)

    # initial scan for low quality with median SD
    baf.sd <- sdByScanChromWindow(blData, genoData)
    med.baf.sd <- medianSdOverAutosomes(baf.sd)
    low.qual.ids <- med.baf.sd$scanID[med.baf.sd$med.sd > 0.05]

    # segment and filter BAF
    scan.ids <- illuminaScanADF$scanID[1:2]
    chrom.ids <- unique(illuminaSnpADF$chromosome)
    snp.ids <- illuminaSnpADF$snpID[illuminaSnpADF$missing.n1 < 1]
    data(centromeres.hg18)
    anom <- anomDetectBAF(blData, genoData, scan.ids=scan.ids, chrom.ids=chrom.ids,
      snp.ids=snp.ids, centromere=centromeres.hg18, low.qual.ids=low.qual.ids)

    # further screen for low quality scans
    snp.annot <- illuminaSnpADF
    snp.annot$eligible <- snp.annot$missing.n1 < 1
    low.qual <- anomIdentifyLowQuality(snp.annot, med.baf.sd, anom$seg.info,
      sd.thresh=0.1, sng.seg.thresh=0.0008, auto.seg.thresh=0.0001)

    close(blData)
    close(genoData)

[Package GWASTools version 1.36.0 Index]