StrandOddsRatio (gatk 4.1.7.0 API)

java.lang.Object
- org.broadinstitute.hellbender.tools.walkers.annotator.VariantAnnotation
- - org.broadinstitute.hellbender.tools.walkers.annotator.InfoFieldAnnotation
  - - org.broadinstitute.hellbender.tools.walkers.annotator.StrandBiasTest
    - - org.broadinstitute.hellbender.tools.walkers.annotator.StrandOddsRatio

All Implemented Interfaces:

Annotation, StandardAnnotation
```
@DocumentedFeature(groupName="Variant Annotations",
                   groupSummary="Available to HaplotypeCaller, Mutect2, VariantAnnotator and GenotypeGVCFs. See https://software.broadinstitute.org/gatk/documentation/article?id=10836",
                   summary="Strand bias estimated by the symmetric odds ratio test (SOR)")
public final class StrandOddsRatio
extends StrandBiasTest
implements StandardAnnotation
```
Strand bias estimated by the Symmetric Odds Ratio test
Strand bias is a type of sequencing bias in which one DNA strand is favored over the other, which can result in incorrect evaluation of the amount of evidence observed for one allele vs. the other. The StrandOddsRatio annotation is one of several methods that aims to evaluate whether there is strand bias in the data. It is an updated form of the Fisher Strand Test that is better at taking into account large amounts of data in high coverage situations. It is used to determine if there is strand bias between forward and reverse strands for the reference or alternate allele(s).

Statistical notes

The following 2x2 contingency table gives the notation for allele support and strand orientation.

+ strand    - strand

REF    X[0][0] X[0][1]

ALT    X[1][0] X[1][1]

We can then represent the Odds Ratios with the equation:

and its inverse:

The sum R + 1/R is used to detect a difference in strand bias for REF and for ALT. The sum makes it symmetric. A high value is indicative of large difference where one entry is very small compared to the others. A scale factor of refRatio/altRatio where

and

ensures that the annotation value is large only. The final SOR annotation is given in natural log space.

See the method document on statistical tests for a more detailed explanation of this statistical test.

Example calculation

Here is a variant record where SOR is 0.592.
```
     AC=78;AF=2.92135e-02;AN=2670;DP=31492;FS=48.628;MQ=58.02;MQRankSum=-2.02400e+00;MQ_DP=3209;QD=3.03; \
     ReadPosRankSum=-1.66500e-01;SB_TABLE=1450,345,160,212;SOR=0.592;VarDP=2167
 
```
Read support shows some strand bias for the reference allele but not the alternate allele. The SB_TABLE annotation (a non-GATK annotation) indicates 1450 reference alleles on the forward strand, 345 reference alleles on the reverse strand, 160 alternate alleles on the forward strand and 212 alternate alleles on the reverse strand. The tool uses these counts towards calculating SOR. To avoid multiplying or dividing by zero values, the tool adds one to each count.
```
 refFw = 1450 + 1 = 1451
 refRv = 345 + 1 = 346
 altFw = 160 + 1 = 161
 altRv = 212 + 1 = 213
 
```
Calculate SOR with the following.

$SOR = ln(symmetricalRatio) + ln(refRatio) - ln(altRatio)$

where

$symmetricalRatio = R + \frac{1}{R}$

$R = \frac{(\frac{refFw}{refRv})}{(\frac{altFw}{altRv})} = \frac{(refFw*altRv)}{(altFw*refRv)}$

$refRatio = \frac{(smaller\;of\;refFw\;and\;refRv)}{(larger\;of\;refFw\;and\;refRv)}$

and

$altRatio = \frac{(smaller\;of\;altFw\;and\;altRv)}{(larger\;of\;altFw\;and\;altRv)}$

Fill out the component equations with the example counts to calculate SOR.
```
 symmetricalRatio  = (1451*213)/(161*346) + (161*346)/(1451*213) = 5.7284
 refRatio = 346/1451 = 0.2385
 altRatio = 161/213 = 0.7559
 SOR = ln(5.7284) + ln(0.2385) - ln(0.7559) = 1.7454427755 + (-1.433) - (-0.2798) = 0.592
 
```
Related annotations
- AS_StrandOddsRatio allele-specific strand bias estimated by the symmetric odds ratio test.
- StrandBiasBySample outputs counts of read depth per allele for each strand orientation.
- FisherStrand uses Fisher's Exact Test to evaluate strand bias.

	+ strand	- strand
REF	X[0][0]	X[0][1]
ALT	X[1][0]	X[1][1]

Field Summary
- Fields inherited from class org.broadinstitute.hellbender.tools.walkers.annotator.StrandBiasTest
  ARRAY_DIM, ARRAY_SIZE

Constructor Summary

Constructors
Constructor and Description

StrandOddsRatio()

Constructors
Constructor and Description
`StrandOddsRatio()`

Method Summary

All Methods Static Methods Instance Methods Concrete Methods
Modifier and Type	Method and Description
`protected java.util.Map<java.lang.String,java.lang.Object>`	`calculateAnnotationFromGTfield(htsjdk.variant.variantcontext.GenotypesContext genotypes)`
`protected java.util.Map<java.lang.String,java.lang.Object>`	`calculateAnnotationFromLikelihoods(AlleleLikelihoods<GATKRead,htsjdk.variant.variantcontext.Allele> likelihoods, htsjdk.variant.variantcontext.VariantContext vc)`
`static double`	`calculateSOR(int[][] table)` Computes the SOR value of a table after augmentation.
`static java.lang.String`	`formattedValue(double sor)`
`java.util.List<java.lang.String>`	`getKeyNames()` Return the keys

Methods inherited from class org.broadinstitute.hellbender.tools.walkers.annotator.StrandBiasTest
annotate, decodeSBBS, getContingencyTable, getContingencyTable, getStrandCounts, getTableFromSamples, passesMinimumThreshold

Methods inherited from class org.broadinstitute.hellbender.tools.walkers.annotator.InfoFieldAnnotation
getDescriptions

Methods inherited from class org.broadinstitute.hellbender.tools.walkers.annotator.VariantAnnotation
toString

Methods inherited from class java.lang.Object
clone, equals, finalize, getClass, hashCode, notify, notifyAll, wait, wait, wait

- Constructor Detail
  - StrandOddsRatio
```
public StrandOddsRatio()
```
- Method Detail
  - calculateAnnotationFromGTfield
```
protected java.util.Map<java.lang.String,java.lang.Object> calculateAnnotationFromGTfield(htsjdk.variant.variantcontext.GenotypesContext genotypes)
```
    Specified by:
    
    calculateAnnotationFromGTfield in class StrandBiasTest
  - calculateAnnotationFromLikelihoods
```
protected java.util.Map<java.lang.String,java.lang.Object> calculateAnnotationFromLikelihoods(AlleleLikelihoods<GATKRead,htsjdk.variant.variantcontext.Allele> likelihoods,
                                                                                              htsjdk.variant.variantcontext.VariantContext vc)
```
    Specified by:
    
    calculateAnnotationFromLikelihoods in class StrandBiasTest
  - calculateSOR
```
public static double calculateSOR(int[][] table)
```
    Computes the SOR value of a table after augmentation. Based on the symmetric odds ratio but modified to take on low values when the reference +/- read count ratio is skewed but the alt count ratio is not. Natural log is taken to keep values within roughly the same range as other annotations. Adding pseudocounts avoids division by zero.
    
    Parameters:
    
    table - The table before adding pseudocounts
    
    Returns:
    
    the SOR annotation value
  - formattedValue
```
public static java.lang.String formattedValue(double sor)
```
  - getKeyNames
```
public java.util.List<java.lang.String> getKeyNames()
```
    Description copied from class: VariantAnnotation
    
    Return the keys
    
    Specified by:
    
    getKeyNames in class VariantAnnotation

Class StrandOddsRatio

Statistical notes

Example calculation

Related annotations

Field Summary

Fields inherited from class org.broadinstitute.hellbender.tools.walkers.annotator.StrandBiasTest

Constructor Summary

Method Summary

Methods inherited from class org.broadinstitute.hellbender.tools.walkers.annotator.StrandBiasTest

Methods inherited from class org.broadinstitute.hellbender.tools.walkers.annotator.InfoFieldAnnotation

Methods inherited from class org.broadinstitute.hellbender.tools.walkers.annotator.VariantAnnotation

Methods inherited from class java.lang.Object

Constructor Detail

StrandOddsRatio

Method Detail

calculateAnnotationFromGTfield

calculateAnnotationFromLikelihoods

calculateSOR

formattedValue

getKeyNames