library("trioClasses")
library("GWASTools")
library("CleftCNVAssoc")
First we create a vector of offspring IDs that we want plotted.
offspring.vec <- as.character(completeTrios(fe.beaty)$id)
Now we incorporate it into a GRange object with the ranges in this case being the chr16 region for each of the offspring.
gr <- GRanges(seqnames = rep("chr16", length(offspring.vec)), ranges = IRanges(start = 32404517,
end = 32530051), id = offspring.vec)
Now we apply a function from CleftCNVAssoc to retrieve data from GWASTools objects. These data exist only on an encrypted hard drive and enigma.
raw.df.list <- getRaw(gr + 1e+06, intensfile = intensfile, snpAnnot = beaty_snpAnnot,
scan.id = scan.ids, fa.id = fa.id, ma.id = ma.id, genofile = genofile, xyfile = xyfile)
Here are the data for the first offspring's first 5 markers.
head(raw.df.list[[1]], 5)
logr baf pos logr.fa logr.ma baf.fa baf.ma geno geno.fa
1 0.1662 1.0000 31405309 0.2031 0.0326 1.0000 1.0000 0 0
2 0.3557 1.0000 31405382 0.4870 0.2167 1.0000 1.0000 0 0
3 0.0232 0.9853 31411252 0.0954 -0.0743 0.4786 0.9795 0 1
4 0.1978 0.9981 31428777 0.1213 0.1274 1.0000 1.0000 0 0
5 0.0435 0.0057 31435321 -0.1137 0.1395 0.0071 0.5640 2 2
geno.ma x y x.fa y.fa x.ma y.ma snpname
1 0 0.000 1.310 0.000 1.344 0.000 1.194 rs3813007
2 0 0.031 0.734 0.036 0.802 0.025 0.668 rs3813008
3 0 0.194 1.769 1.349 1.270 0.194 1.647 rs4536493
4 0 0.020 0.875 0.005 0.837 0.013 0.836 rs4889545
5 1 1.246 0.058 1.116 0.055 0.763 1.003 rs4477723
Plot the logR values for everyone stratified by F,M,O. Purple is offspring, red is father, and blue is mother.
Not very informative so we turn to individual trios with an untransmitted deletion. First, we need to find a vector offspring IDs with an untransmitted deletion. This is a property of the CNVMatrix within the FamilyExperiment object and can be manipulated with the non-exported method TrioAssay. To begin we first subset the CNVMatrix on the chr16 region.
chr16.gr <- GRanges(seqnames = "chr16", ranges = IRanges(start = 32404517, end = 32530051))
(fe.beaty.chr16 <- fe.beaty[queryHits(findOverlaps(rowData(fe.beaty), chr16.gr))])
class: FamilyExperiment
dim: 123 1339
exptData(0):
assays(1): cnv
rownames(123): comp5899 comp5900 ... comp6020 comp6021
rowData metadata column names(0):
colnames(1339): 11005_01@1008472480 11005_02@1008472482 ...
18117_02@0070298660 18117_03@0070298657
colData names(1): id
pedigree(2082): famid id fid mid sex dx
complete trios(445):
Now with the smaller FE object we can easily construct the trio-states.
trioAssay.chr16 <- trioClasses:::TrioAssay(fe.beaty.chr16, type = "cnv")
trioStates.chr16 <- with(trioAssay.chr16, matrix(paste0(F, M, O), nrow = nrow(O),
ncol = ncol(O)))
dimnames(trioStates.chr16) <- dimnames(trioAssay.chr16$O)
head(trioStates.chr16[, 1:5], 10)
comp5899 comp5900 comp5901 comp5902 comp5903
11005_01@1008472480 "000" "000" "000" "000" "000"
11021_01@1008472417 "000" "000" "000" "000" "000"
11035_01@1008471376 "000" "000" "000" "000" "000"
12002_01@1008489061 "000" "000" "000" "000" "000"
12004_01@1008489060 "000" "000" "000" "000" "000"
12005_01@1008490117 "000" "000" "000" "000" "000"
12008_01@1008490140 "010" "010" "010" "010" "010"
12014_01@1008490162 "000" "000" "000" "000" "000"
12015_01@1008490100 "001" "001" "001" "001" "001"
12017_01@1008489083 "000" "000" "000" "000" "000"
Now we identify trio-cnv pairs with an untransmitted deletion, i.e., trio-states 100, 010, or 110. (This is not a complete list of trio-states with a non-transmission.)
untrans.mat <- matrix(trioStates.chr16 %in% c("100", "010", "110"), nrow = nrow(trioStates.chr16),
ncol = ncol(trioStates.chr16), byrow = FALSE, dimnames = dimnames(trioStates.chr16))
head(untrans.mat[, 1:10], 10)
comp5899 comp5900 comp5901 comp5902 comp5903 comp5904
11005_01@1008472480 FALSE FALSE FALSE FALSE FALSE FALSE
11021_01@1008472417 FALSE FALSE FALSE FALSE FALSE FALSE
11035_01@1008471376 FALSE FALSE FALSE FALSE FALSE FALSE
12002_01@1008489061 FALSE FALSE FALSE FALSE FALSE FALSE
12004_01@1008489060 FALSE FALSE FALSE FALSE FALSE FALSE
12005_01@1008490117 FALSE FALSE FALSE FALSE FALSE FALSE
12008_01@1008490140 TRUE TRUE TRUE TRUE TRUE TRUE
12014_01@1008490162 FALSE FALSE FALSE FALSE FALSE FALSE
12015_01@1008490100 FALSE FALSE FALSE FALSE FALSE FALSE
12017_01@1008489083 FALSE FALSE FALSE FALSE FALSE FALSE
comp5905 comp5906 comp5907 comp5908
11005_01@1008472480 FALSE FALSE FALSE FALSE
11021_01@1008472417 FALSE FALSE FALSE FALSE
11035_01@1008471376 FALSE FALSE FALSE FALSE
12002_01@1008489061 FALSE FALSE FALSE FALSE
12004_01@1008489060 FALSE FALSE FALSE FALSE
12005_01@1008490117 FALSE FALSE FALSE FALSE
12008_01@1008490140 TRUE TRUE TRUE TRUE
12014_01@1008490162 FALSE FALSE FALSE TRUE
12015_01@1008490100 FALSE FALSE FALSE FALSE
12017_01@1008489083 TRUE TRUE TRUE TRUE
And finally we find the IDs of those with more than zero untransmitted deletions.
offspring.chr16 <- rownames(untrans.mat)[which(rowSums(untrans.mat) > 0)]
length(offspring.chr16)
[1] 140
head(offspring.chr16)
[1] "12008_01@1008490140" "12014_01@1008490162" "12017_01@1008489083"
[4] "12021_01@1008490126" "12024_01@1008490151" "12027_01@1008490157"
Now we have what we need to dig deeper into the cause of the under-transmission.
Now for the transmitted deletions in the chr16 region.
trans.mat <- matrix(trioStates.chr16 %in% c("101", "011", "112"), nrow = nrow(trioStates.chr16),
ncol = ncol(trioStates.chr16), byrow = FALSE, dimnames = dimnames(trioStates.chr16))
offspring.chr16 <- rownames(trans.mat)[which(rowSums(trans.mat) > 0)]
length(offspring.chr16)
[1] 69
head(offspring.chr16)
[1] "12008_01@1008490140" "12014_01@1008490162" "12054_01@1008494951"
[4] "12062_01@0067868215" "12064_01@0067868240" "12071_01@0067868170"
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