Package ‘relMix’

April 23, 2024

Type Package
Title Relationship Inference for DNA Mixtures
Version 1.4
Date 2024-04-12
Description Analysis of DNA mixtures involving relatives by computation of likelihood ratios that ac-
count for dropout and drop-in, mutations, silent alleles and population
substructure. This is useful in kinship cases, like non-invasive prenatal paternity test-
ing, where deductions about individuals' relationships rely on DNA mixtures,
and in criminal cases where the contributors to a mixed DNA stain may be related. Relation-
ships are represented
by pedigrees and can include kinship between more than two individuals. The main func-
tion is relMix() and its graphical user interface relMixGUI().
The implementation and method is described in Dorum et al. (2017) <doi:doi.org/10.1007/s00414-
016-1526-x>, Hernandis et al. (2019)
<doi:doi.org/10.1016/j.fsigss.2019.09.085> and Kaur et al. (2016) <doi:doi.org/10.1007/s00414-
015-1276-1>.
VignetteBuilder knitr
Encoding UTF-8
Depends R (>= 3.5.0)
Imports Familias (>= 2.6.1), gWidgets2, gWidgets2tcltk, flextable,
officer, pedFamilias, pedtools
Suggests knitr, pander, rmarkdown, tkrplot
License GPL (>= 2)
RoxygenNote 7.2.3

URL https://gdorum.github.io/relMix/
NeedsCompilation no
Author Guro Dorum [aut, cre],
Elias Hernandis [aut],
Navreet Kaur [ctb],
Thore Egeland [ctb]
Maintainer Guro Dorum <[email protected]>

1
2 allGenos

Repository CRAN
Date/Publication 2024-04-23 10:50:02 UTC

R topics documented:
allGenos . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
checkFrequenciesFile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
checkMixtureFile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
checkPedigreeFile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
checkReferenceFile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
createDatamatrix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
db . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
db2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
generateMix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
mixLikDrop . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
relMix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
relMixGUI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Index 16

allGenos Find all possible genotypes

Description
Finds all possible genotypes based on input alleles.

Usage
allGenos(alleles)

Arguments
alleles Vector of input alleles, numeric or character

Value
Matrix of all possible genotypes, one row per genotype

Author(s)
Guro Dorum

Examples
alleles <- 1:3
allGenos(alleles)
checkFrequenciesFile 3

checkFrequenciesFile Load and check a frequency file

Description

Loads a frequency database file and compares it against mixture data to check for common errors.

Usage

checkFrequenciesFile(filename, mix)

Arguments

filename Path of the frequency database file

mix Data frame with mixture data. See relMix vignette for description of the format

Details

The mixture data is used to perform more advanced checks, such as to make sure all alleles present
in the mixture file have an entry in the frequency database. If warnings are found, the function
attempts to fix them and explains what it has done in the warning messages. If an error is found,
checking stops and a NULL data frame is returned. The error is described in the error messages.

Value

A list containing

• df Data frame with frequencies

• warning List of strings describing the errors that occurred but could be fixed or that do not
prevent the execution of the program.
• error List of strings describing the errors that occurred that made it impossible to return a
valid data frame. If this list is not empty, then the data frame item will be NULL

Author(s)

Elias Hernandis

See Also

checkMixtureFile for information on how to load a mixture file.

4 checkMixtureFile

Examples
mixfile <- system.file("extdata","mixture.txt",package="relMix")
mix <- checkMixtureFile(mixfile)
# note: the mixture data frame is passed as an argument
# if the previous check failed, the program should not continue
# with the frequencies file check
freqfile <- system.file('extdata','frequencies22Markers.txt',package='relMix')
freqs <- checkFrequenciesFile(freqfile, mix$df)

checkMixtureFile Load and check a mixture file

Description

Given a mixture file name, returns the loaded data frame along with any detected errors or warnings.

Usage

checkMixtureFile(filename)

Arguments

filename Path of the mixture file

Details

If warnings are found, the function attempts to fix them and explains what it has done in the warning
messages. If an error is found, checking stops and a NULL data frame is returned. The error is
described in the error messages.

Value

A list containing

• df The loaded data frame, NULL if errors are present.

• warning A list of strings describing the errors that ocurred but could be fixed or that do not
prevent the execution of the program.
• error A list of strings describing the errors that occurred that made it impossible to return a
valid data frame. If this list is not empty, then the data frame item will be null.

Author(s)

Elias Hernandis
checkPedigreeFile 5

Examples
mixfile <- system.file("extdata","mixture.txt",package="relMix")
result <- checkMixtureFile(mixfile);
print(result$df);
print(result$warning);
print(result$error);

checkPedigreeFile Check a pedigree file

Description
Given a pedigree file path the function attempts to load it and compare it to the reference profiles to
detect possible errors.

Usage
checkPedigreeFile(filename, df)

Arguments
filename Path of the pedigree file
df Data frame with reference profiles

Details
The pedigree file must be a a text file in ped format (see the relMix vignette for an example).
The data frame with reference data is used to compare names of individuals and detect possible
misspellings. If warnings are found, the function attempts to fix them and explains what it has done
in the warning messages. If an error is found, checking stops. The error is described in the error
messages.

Value
A list containing

• df A list of class [Familias::FamiliasPedigree()], or NULL if errors are present.

• warning A list of strings describing the errors that ocurred but could be fixed or that do not
prevent the execution of the program.
• error A list of strings describing the errors that ocurred that made it imposible to return a
valid data frame. If this list is not empty, then the dataframe item will be null.

Author(s)
Elias Hernandis
6 checkReferenceFile

Examples
#First load mixture file
mixfile <- system.file("extdata","mixture_silent_ex.txt",package="relMix")
mix <- checkMixtureFile(mixfile);
#Load reference file
reffile <- system.file("extdata","references_silent.txt",package="relMix")
ref <- checkReferenceFile(reffile, mix$df)
#Check pedigree file
pedfile <- system.file("extdata","custom_pedigree_maternity_duo.ped",package="relMix")
checkPedigreeFile(pedfile,ref$df);

checkReferenceFile Check a reference profiles file

Description
Given a reference profile file name the function attempts to load it and compare it to the mixture file
to detect possible errors.

Usage
checkReferenceFile(filename, mix)

Arguments
filename Path of the reference profiles file
mix Data frame with mixture data

Details
See the relMix vignette for a description of the format of the reference file. The data frame with
mixture data is used to compare If warnings are found, the function attempts to fix them and ex-
plains what it has done in the warning messages. If an error is found, checking stops and a NULL
dataframe is returned. The error is described in the error messages.

Value
A list containing
• df The loaded data frame, NULL if errors are present
• warning A list of strings describing the errors that ocurred but could be fixed or that do not
prevent the execution of the program.
• error A list of strings describing the errors that ocurred that made it impossible to return a
valid data frame. If this list is not empty, then the data frame item will be null.

Author(s)
Elias Hernandis
createDatamatrix 7

See Also
checkMixtureFile for information on how to load a mixture file.

Examples
#Load a mixture file
mixfile <- system.file("extdata","mixture.txt",package="relMix")
mix <- checkMixtureFile(mixfile);
#Note: the mixture dataframe is passed as an argument. If the previous check failed,
#the program should not continue with the reference file check
reffile <- system.file("extdata","references.txt",package="relMix")
checkReferenceFile(reffile, mix$df);

createDatamatrix Create data matrix with possible genotype combinations for specified
individuals

Description
A data matrix of genotypes for known individuals and all possible genotypes for unknown individ-
uals is created.

Usage
createDatamatrix(locus, knownGenos, idsU = NULL)

Arguments
locus A list of class FamiliasLocus containing information about the locus
knownGenos List of known genotypes. Each element is a vector with genotype for one indi-
vidual. The elements must be named
idsU Vector of indices for unknown individuals

Value
A data matrix of genotypes where each row corresponds to an individual.

Author(s)
Guro Dorum

See Also
FamiliasLocus.
8 db

Examples
#Define alleles and frequencies
alleles <- 1:2
afreq <- c(0.5,0.5)
#Create locus object
locus <- Familias::FamiliasLocus(frequencies=afreq,name="M1",allelenames= alleles)
#Known genotypes of alleged father and mother, child's genotype is uknown
gAF <- c(1,1)
gMO <- c(1,1)
datamatrix <- createDatamatrix(locus,knownGenos=list(AF=gAF,MO=gMO),idsU=c("CH"))

db Allele database

Description
Norwegian database with 17 EXS17 markers and 6 additional markers.

Usage
data(db)

Format
A data frame with 324 observations on the following 3 variables:

Marker a factor with levels corresponding to name of markers

Allel a numeric vector denoting allele
Frequency a numeric vector in (0,1)

Source
Dupuy et al. (2013), unpublished.

Examples
data(db)
#Checks that frequencies add to 1
lapply(split(db$Frequency,db$Marker),sum)
#Finds number of alleles for all markers
unlist(lapply(split(db$Frequency,db$Marker),length))
#A closer look at the marker SE33
SE33=db[db$Marker=="SE33",]
barplot(SE33$Frequency)
db2 9

db2 Allele database for 22 markers

Description
Frequencies for 22 loci from the prototype 24-plex STR panel from Thermo Fisher.

Usage
data(db2)

Format
A data frame with 206 observations on the following 3 variables.

Marker a factor with levels corresponding to name of markers

Allele a numeric vector denoting allele
Frequency a numeric vector in (0,1)

Details
The format is convenient for R.

Source
Hill et al. (2013) U.S. population data for 29 autosomal STR loci. Forensic Sci. Int. Genet. 7,
e82-e83.
Hill et al. (2006) Allele Frequencies for 26 MiniSTR Loci with U.S. Caucasian, African American,
and Hispanic Populations. http://www.cstl.nist.gov/biotech/strbase/NISTpop.htm

Examples
data(db2)

generateMix Create a mixture of genotypes with simulated drop-in and dropout

Description
Takes as input genotypes and creates a mixture. Alleles drop in and out of the mixture with the
specified probabilities

Usage
generateMix(G, alleles, afreq, D, di)
10 mixLikDrop

Arguments

G List of genotypes. Each element is a vector with genotype for one individual
alleles Numeric or character Vector of allele names for the marker
afreq Numeric vector of allele frequencies for the marker
D List of dropout values (between 0 and 1) per contributor. Each element is a vec-
tor containing heterozygous and homozygous dropout probability for the given
contributor
di Drop-in value (between 0 and 1)

Value

A vector of mixture alleles.

Author(s)

Guro Dorum

Examples
#Define alleles and frequencies
alleles <- 1:2
afreq <- c(0.5,0.5)
#Genotypes
gM <- c(1,1)
gC <- c(1,2)
#Dropout and drop-in values
d <- 0.1
di <- 0.05
#No drop-in for first contributor
D <- list(c(0,0),c(d,d^2))
R <- generateMix(G=list(gM,gC),alleles,afreq,D=D,di=di)

mixLikDrop Likelihoods for DNA mixtures with dropout and dropin

Description

Computes the likelihood of a mixture conditioned on a given number of known and unknown con-
tributors, and drop-in and dropout probabilities.

Usage

mixLikDrop(R, G, D, di = 0, alleleNames, afreq)

mixLikDrop 11

Arguments

R Vector of mixture alleles

G List of genotypes. Each element is a vector with genotype for one individual
D List of dropout values (between 0 and 1) per contributor. Each element is a vec-
tor containing heterozygous and homozygous dropout probability for the given
contributor
di Drop-in value (between 0 and 1)
alleleNames Vector of allele names for the marker
afreq Vector of allele frequencies for the marker

Value

The likelihood (a numeric)

Author(s)

Guro Dorum

References

The model is specified in the appendix of Haned et al. (2012) <doi:10.1016/j.fsigen.2012.08.008>.

See Also

relMix

Examples
#Define alleles and frequencies
alleles <- 1:2
afreq <- c(0.5,0.5)
#Genotypes
gM <- c(1,1)
gC <- c(1,2)
#Mixture alleles
R <- c(1,2)
#Dropout and drop-in values
d <- 0.1
di <- 0.05
#No drop-in for first contributor
D <- list(c(0,0),c(d,d^2))
mixLikDrop(R=R,G=list(gM,gC),D=D,di=di,alleleNames=alleles,afreq=afreq)
12 relMix

relMix Relationship inference based on mixtures

Description
Calculates likelihoods for relationship inference involving mixtures and missing reference profiles,
including drop-in and dropout, mutations, silent alleles and theta correction.

Usage
relMix(
pedigrees,
locus,
R,
datamatrix,
ids,
D = rep(list(c(0, 0)), length(ids)),
di = 0,
kinship = 0
)

Arguments
pedigrees A list of pedigrees defined using FamiliasPedigree
locus A list of class FamiliasLocus containing information about the locus. Note that
a silent allele must be indicated by ’s’ (and not ’silent’ as in Familias)
R A vector of mixture alleles, or a list of such if there are multiple replicates
datamatrix A data frame where each line corresponds to one constellation of genotypes for
the involved individuals. Indices of individuals must be given as rownames and
must correspond to indices in the pedigree
ids Index vector indicating which individuals are contributors to the mixture. The
indices must correspond to indices in the pedigree
D List of numeric dropout values (between 0 and 1) per contributor. Each element
is a vector containing heterozygous and homozygous dropout probability for the
given contributor
di A numeric drop-in value (between 0 and 1)
kinship A numeric value between 0 and 1 that defines the theta-parameter

Details
The function requires the package Familias and calls on the function FamiliasPosterior.

Value
A numeric likelihood for each pedigree named according to the pedigrees, and a matrix of likeli-
hoods for each pedigree and each term (genotype constellation) considered in the calculation (one
row per term).
relMix 13

Author(s)
Navreet Kaur, Thore Egeland, Guro Dorum

References
Dorum et al. (2017) <doi:10.1007/s00414-016-1526-x>
Kaur et al. (2016) <doi:10.1007/s00414-015-1276-1>

See Also
relMixGUI for the GUI version of relMix, FamiliasLocus on how to create a FamiliasLocus and
FamiliasPedigree on how to create a FamiliasPedigree.

Examples
#Example 1: paternity trio with mixture of mother and child
#Define alleles and frequencies
alleles <- 1:2
afreq <- c(0.4,0.6)
#Define pedigrees
persons <- c("CH","MO","AF")
ped1 <- Familias::FamiliasPedigree(id=persons, dadid=c("AF",NA, NA), momid=c("MO", NA,NA),
sex=c("male", "female", "male"))
ped2 <- Familias::FamiliasPedigree(id=c(persons, "TF"), dadid=c("TF", NA, NA,NA),
momid=c("MO", NA, NA,NA), sex=c("male", "female", "male", "male"))
pedigrees <- list(isFather = ped1, unrelated=ped2)
#Create locus object
locus <- Familias::FamiliasLocus(frequencies=afreq,name="M1",
allelenames= alleles)
#Known genotypes of alleged father and mother
gAF <- c(1,1)
gMO <- c(1,1)
#Mixture alleles
R <- c(1,2)
datamatrix <- createDatamatrix(locus,knownGenos=list(AF=gAF,MO=gMO),idsU=c("CH"))
#Define dropout and drop-in values
d <- 0.1
di <- 0.05
res <- relMix(pedigrees, locus, R, datamatrix, ids=c("MO","CH"),
D=list(c(0,0),c(d,d^2)),di=di, kinship=0)
#LR=0.054
res$isFather/res$unrelated

#Example 2: Exhaustive example with silent allele, mutations, dropout and drop-in
#H1: Contributors are mother and child
#H2: Contributors are mother and unrelated
#Possible dropout in both contributors
gMO <- c(1,1) #Mother's genotype
R <- 1 #Mixture alleles
#Mother/child pedigree
persons <- c("CH","MO")
14 relMixGUI

ped1 <- Familias::FamiliasPedigree(id=persons, dadid=c(NA,NA), momid=c("MO", NA),

sex=c("male", "female"))
ped2 <- Familias::FamiliasPedigree(id=c(persons), dadid=c(NA, NA),
momid=c( NA, NA),
sex=c("male", "female"))
pedigrees <- list(H1 = ped1, H2=ped2)
#Alleles and frequencies:
#When silent alleles are involved, a custom mutation matrix is required.
#No mutations are possible to or from silent alleles.
#We create the mutation model with FamiliasLocus and modify it before it is
#passed on to relMix
alleles <- c(1,2,'silent')
afreq <- c(0.4,0.5,0.1)
#Create initial locus object with mutation matrix
locus <- Familias::FamiliasLocus(frequencies=afreq,name='M1',
allelenames= alleles, MutationModel='Equal',
femaleMutationRate=0.1,maleMutationRate=0.1)
#Modify mutation matrix from Familias:
#Silent allele must be given as 's' (not 'silent' as in Familias)
newAlleles <- c(alleles[-length(alleles)],'s')
mm <- locus$femaleMutationMatrix
colnames(mm) <- rownames(mm) <- newAlleles
#Create new locus object with modified mutation matrix
locus <- Familias::FamiliasLocus(frequencies=afreq,name='M1',
allelenames= newAlleles, MutationModel='Custom', MutationMatrix=mm)
knownGenos <- list(gMO)
names(knownGenos) <- c("MO")
datamatrix <- createDatamatrix(locus,knownGenos,ids="CH")
d <- 0.1 #Dropout probability for both contributors
di <- 0.05
res2 <- relMix(pedigrees, locus, R, datamatrix, ids=c("MO","CH"),
D=list(c(d,d^2),c(d,d^2)),di=di, kinship=0)
#LR=1.68
res2$H1/res2$H2

relMixGUI GUI for relMix

Description
User-friendly graphical user interface for relMix.

Usage
relMixGUI()

Details
Includes error checking for the input files.
relMixGUI 15

Value
No return value, called for side effects.

Author(s)
Guro Dorum, Elias Hernandis

See Also
relMix for the main function implemented in relMixGUI.

Examples
#Examples can be found in the vignette and example data files can be found
#in the folder "extdata" in the installation folder for relMix
Index

∗ datasets
db, 8
db2, 9

allGenos, 2

checkFrequenciesFile, 3
checkMixtureFile, 3, 4, 7
checkPedigreeFile, 5
checkReferenceFile, 6
createDatamatrix, 7

db, 8
db2, 9

Familias, 12
FamiliasLocus, 7, 12, 13
FamiliasPedigree, 12, 13
FamiliasPosterior, 12

generateMix, 9

mixLikDrop, 10

relMix, 11, 12, 15

relMixGUI, 13, 14

16