gKinship: Generalised kinship coefficients

In magnusdv/ribd: Pedigree-based Relatedness Coefficients

Generalised kinship coefficients

Description

Computes single-locus generalised kinship coefficients of various kinds. These are fundamental for computing identity coefficients (see identityCoefs()), but are also interesting in their own right. Each generalised kinship coefficient is defined as the probability of observing a corresponding generalised IBD pattern, as defined and discussed in the Details section below.

Usage

gKinship(
  x,
  pattern,
  distinct = TRUE,
  Xchrom = FALSE,
  method = c("auto", "K", "WL", "LS", "GC"),
  verbose = FALSE,
  debug = FALSE,
  mem = NULL,
  ...
)

gip(x, pattern, distinct = TRUE)

Arguments

x	A ped object.
pattern	A gip object, or a list of vectors to be passed onto gip(). Each vector should contain members of x constituting an IBD block. (See Details and Examples.)
distinct	A logical indicating if different blocks are required to be non-IBD. Default: TRUE. (Irrelevant for single-block patterns.)
Xchrom	A logical, by default FALSE.
method	Either "auto", "K", "WL", "LS" or "GC".
verbose	A logical, by default FALSE.
debug	A logical, by default FALSE.
mem	For internal use.
...	Further arguments.

Details

The starting point: standard kinship coefficients

The classical kinship coefficient phi between two pedigree members A and B, is the probability that two alleles sampled from A and B (one from each), at a random autosomal locus, are identical by descent (IBD).

In the language and notation to be introduced shortly, we would write ⁠phi = Pr[(A,B)]⁠ where ⁠(A,B)⁠ is an IBD pattern.

Generalised IBD patterns

We define a generalised IBD pattern (GIP) to be a partition of a set of alleles drawn from members of a pedigree, such that the alleles in each subset are IBD. Each subset (also referred to as a group or a block) is written as a collection of pedigree members (A, B, ...), with the understanding that each member represents one of its alleles at the given locus. A member may occur in multiple blocks, and also more than once within a block.

Additional requirements give rise to different flavours of GIPs (and their corresponding coefficients):

• Distinct (resp. non-distinct): alleles in different blocks are non-IBD (resp. may be IBD)

• Deterministic (resp. random): the parental origin (paternal or maternal) of each allele is fixed (resp. unknown).

We may say that a GIP is partially (rather than fully) deterministic if the parental origin is fixed for some, but not all alleles involved.

Notational examples

Our notation distinguishes the different types of patterns, as exemplified below. Blocks are separated with "/" if they are distinct, and "&" otherwise. Deterministically sampled alleles are suffixed by either ":p" (paternal) or ":m" (maternal).

• ⁠(A, B) & (A, C)⁠: 4 alleles are sampled randomly; two from A, one from B and one from C. The first from A is IBD with that from B, and the second from A is IBD with that from C. All four alleles may be IBD. [Random, non-distinct]

• ⁠(A, B) / (A, C)⁠: Same as the previous, but the two allele pairs must be non-IBD. [Random, distinct]

• ⁠(A:p, C:p) / (C:m)⁠: The paternal alleles of A and C are IBD, and different from the maternal allele of C. [Deterministic, distinct]

• ⁠(A, C:p) & (B, C:m)⁠: The paternal and maternal alleles of C are IBD with random alleles of from A and B, respectively. The two pairs are not necessarily different. [Partially deterministic, non-distinct]

• ⁠(A:p, A, A)⁠: Here we have just one group, specifying that the paternal allele of A is IBD with two other alleles sampled randomly from A. (If A is non-inbred, this must have probability 1/4.) [Partially deterministic, single-block]

In the gip() constructor, deterministic sampling is indicated by naming elements with "p" or "m", e.g., c(p = A) produces (A:p). See Examples for how to create the example patterns listed above.

Internal structure of gip objects

(Note: This section is included only for completeness; gip objects should not be directly manipulated by end users.)

Internally, a GIP is stored as a list of integer vectors, each vector giving the indices of pedigree members constituting an IBD block. In addition, the object has three attributes:

• labs: A character vector containing the names of all pedigree members

• deterministic: A logical, which is TRUE if the pattern is (partially or fully) deterministic

• distinct: A logical.

If deterministic = TRUE, the last digit of each integer encodes the parental origin of the allele (0 = unknown; 1 = paternal; 2 = maternal). For example:

• 12 = the maternal origin of individual 1

• 231 = the paternal allele of individual 23

• 30 = a random allele of individual 3

A brief history of generalised kinship coefficients

The notion of generalised kinship coefficients originated with Karigl (1981) who used a selection of random, non-distinct patterns (in our terminology) to compute identity coefficients.

Weeks & Lange (1988), building on Karigl's work, defined random, distinct patterns in full generality and gave an algorithm for computing the corresponding coefficients.

In a follow-up paper, Lange & Sinsheimer (1992) introduced partially deterministic (distinct) patterns, and used these to compute detailed identity coefficients.

In another follow-up, Weeks et al. (1995) extended the work on random, distinct patterns by Weeks & Lange (1988) to X-chromosomal loci.

Garcia-Cortes (2015) gave an alternative algorithm for the detailed identity coefficients, based on (in our terminology) fully deterministic, non-distinct patterns.

Implemented algorithms

The following are valid options for the methods parameters, and what they implement.

• auto: Chooses method automatically, based on the pattern type.

• K: Karigl's algorithm for random, non-distinct patterns. Only the cases considered by Karigl are currently supported, namely single groups up to length 4, and two groups of length two. The implementation in ribd includes an X-chromosomal version, and allows inbred founders.

• WL: Weeks & Lange's algorithm for random, distinct patterns of any size. [TODO: Include the extension to X by Weeks et al. (1995).]

• LS: Lange & Sinsheimer's algorithm for partially deterministic, distinct patterns of any size. Does not support X, nor patterns involving inbred founders.

• GC: Garcia-Cortes' algorithm for fully deterministic, non-distinct patterns. The current implementation only covers the patterns needed to compute identity coefficients, namely single blocks and two blocks of length two. The original algorithm has been extended to an X-chromosomal version, and to pedigrees with inbred founders.

Value

gKinship() returns a single number, the probability of the given IBD pattern.

gip() returns an object of class gip. This is internally a list of integer vectors, with attributes labs, deterministic and distinct. (See also Details.)

References

• G. Karigl (1981). A recursive algorithm for the calculation of identity coefficients. Ann. Hum. Genet.

• D.E. Weeks & K. Lange (1988). The affected-pedigree-member method of linkage analysis. Am. J. Hum. Genet

• K. Lange & J.S. Sinsheimer (1992). Calculation of genetic identity coefficients. Ann. Hum. Genet.

• D.E. Weeks, T.I. Valappil, M. Schroeder, D.L. Brown (1995) An X-linked version of the affected-pedigree-member method of linkage analysis. Hum Hered.

• L.A. García-Cortés (2015). A novel recursive algorithm for the calculation of the detailed identity coefficients. Gen Sel Evol.

See Also

kinship(), identityCoefs()

Examples

### Trivial examples ###

x = nuclearPed(father = "A", mother = "B", children = "C")

# Random, distinct
patt1 = gip(x, list(c("A", "B"), c("A", "C")))
patt1

# Random, non-distinct
patt2 = gip(x, list(c("A", "B"), c("A", "C")), distinct = FALSE)
patt2

# Fully deterministic, distinct
patt3 = gip(x, list(c(p="A", p="C"), c(m="C")))
patt3

# Partially deterministic, non-distinct`
patt4 = gip(x, list(c("A", p="C"), c("B", m="C")), distinct = FALSE)
patt4

# Partially deterministic, single block
patt5 = gip(x, list(c(p="A", "A", "A")))
patt5

stopifnot(
  gKinship(x, patt1) == 0,      # (since A and B are unrelated)
  gKinship(x, patt2) == 0,      # (same as previous)
  gKinship(x, patt3) == 0.5,    # (only uncertainty is which allele A gave to C)
  gKinship(x, patt4) == 0.25,   # (distinct irrelevant)
  gKinship(x, patt5) == 0.25   # (both random must hit the paternal)
)



### Kappa coefficients via generalised kinship ###

# NB: Much less efficient than `kappaIBD()`; only for validation

kappa_from_gk = function(x, ids, method = "WL") {
  fa1 = father(x, ids[1])
  fa2 = father(x, ids[2])
  mo1 = mother(x, ids[1])
  mo2 = mother(x, ids[2])

  GK = function(...) gKinship(x, list(...), method = method)

  k0 = GK(fa1, fa2, mo1, mo2)
  k1 = GK(c(fa1, fa2), mo1, mo2) + GK(c(fa1, mo2), fa2, mo1) +
       GK(c(mo1, fa2), fa1, mo2) + GK(c(mo1, mo2), fa1, fa2)
  k2 = GK(c(fa1, fa2), c(mo1, mo2)) + GK(c(fa1, mo2), c(mo1, fa2))
  c(k0, k1, k2)
}

y1 = nuclearPed(2); ids = 3:4
stopifnot(kappa_from_gk(y1, ids) == kappaIBD(y1, ids))

y2 = quadHalfFirstCousins(); ids = 9:10
stopifnot(kappa_from_gk(y2, ids) == kappaIBD(y2, ids))


### Detailed outputs and debugging ###

x = fullSibMating(1)

# Probability of sampling IBD alleles from 1, 5 and 6
p1 = gip(x, list(c(1,5,6)))
p1
gKinship(x, p1, method = "K", verbose = TRUE, debug = TRUE)
gKinship(x, p1, method = "WL", verbose = TRUE, debug = TRUE)

# Probability that paternal of 5 is IBD with maternal of 6
p2 = gip(x, list(c(p=5, m=6)))
p2
gKinship(x, p2, method = "LS", verbose = TRUE, debug = TRUE)
gKinship(x, p2, method = "GC", verbose = TRUE, debug = TRUE)

# Probability that paternal of 5 is *not* IBD with maternal of 6
p3 = gip(x, list(c(p=5), c(m=6)), distinct = TRUE)
p3
gKinship(x, p3, method = "LS", verbose = TRUE, debug = TRUE)

magnusdv/ribd documentation built on March 29, 2024, 5:20 a.m.