| Title: | The 'snp.matrix' and 'X.snp.matrix' Classes |
|---|---|
| Description: | Implements classes and methods for large-scale SNP association studies |
| Authors: | Hin-Tak Leung <[email protected]> |
| Maintainer: | Hin-Tak Leung <[email protected]> |
| License: | GPL-3 |
| Version: | 1.71.0 |
| Built: | 2024-07-03 05:17:04 UTC |
| Source: | https://github.com/bioc/chopsticks |
Implements classes and some basic methods for large-scale SNP association studies
| Package: | snpMatrix |
| Version: | 1.2.4 |
| Date: | 2008-03-17 |
| Depends: | R(>= 2.3.0), survival, methods |
| Suggests: | hexbin |
| Enhances: | genetics |
| License: | GNU General Public Licence (GPLv3) |
| URL: | http://www-gene.cimr.cam.ac.uk/clayton/software/ |
| Collate: | ld.with.R ss.R contingency.table.R glm\_test.R ibs.stats.R indata.R ld.snp.R ld.with.R.eml.R misc.R outdata.R qq\_chisq.R read.chiamo.R read.HapMap.R read.snps.pedfile.R single.R structure.R wtccc.sample.list.R wtccc.signals.R xstuff.R zzz.R |
| LazyLoad: | yes |
| biocViews: | Microarray, SNPsAndGeneticVariability |
| Packaged: | Mon Mar 17 11:46:30 2008; david |
| Built: | R 2.7.0; i686-pc-linux-gnu; 2008-03-17 11:47:01; unix |
Index:
X.snp-class Class "X.snp"
X.snp.matrix-class Class "X.snp.matrix"
epsout.ld.snp Function to write an eps file directly to
visualize LD
for.exercise Data for exercise in use of the snpMatrix
package
genotype-class snpMatrix-internal
glm.test.control Set up control object for GLM tests
ibs.stats function to calculate the identity-by-state
stats of a group of samples
ibsCount Count alleles identical by state
ibsDist Distance matrix based on identity by state
(IBS)
ld.snp Function to calculate pairwise D', $r^2$
ld.with function to calculate the LD measures of
specific SNPs against other SNPs
pair.result.ld.snp Function to calculate the pairwise D', $r^2$,
LOD of a pair of specified SNPs
plot.snp.dprime Function to draw the pairwise D' in a eps file
qq.chisq Quantile-quantile plot for chi-squared tests
read.HapMap.data function to import HapMap genotype data as
snp.matrix
read.pedfile.info function to read the accompanying info file of
a LINKAGE ped file
read.snps.chiamo Read genotype data from the output of Chiamo
read.snps.long Read SNP data in long format
read.snps.long.old Read SNP input data in "long" format (old
version)
read.snps.pedfile Read genotype data from a LINKAGE "pedfile"
read.wtccc.signals read normalized signals in the WTCCC signal
file format
row.summary Summarize rows of a snp matrix
single.snp.tests 1-df and 2-df tests for genetic associations
with SNPs
snp-class Class "snp"
snp.cbind Bind together two or more snp.matrix objects
snp.cor Correlations with columns of a snp.matrix
snp.dprime-class Class "snp.dprime" for Results of LD
calculation
snp.lhs.tests Score tests with SNP genotypes as dependent
variable
snp.matrix-class Class "snp.matrix"
snp.pre Pre- or post-multiply a snp.matrix object by a
general matrix
snp.rhs.tests Score tests with SNP genotypes as independent
variable
snpMatrix-package The snp.matrix and X.snp.matrix classes
testdata Test data for the snpMatrix package
write.snp.matrix Write a snp.matrix object as a text file
wtccc.sample.list read the sample list from the header of the
WTCCC signal file format
xxt X.X-transpose for a normalised snp.matrix
Further information is available in the following vignettes:
snpMatrix-vignette |
snpMatrix (source, pdf) |
David Clayton <[email protected]> and Hin-Tak Leung <[email protected]>
Maintainer: David Clayton <[email protected]>
epsout.ld.snp takes an object of snp.matrix class and a given
snp range and depth, draw a eps file to visualize the LD in the same color scheme
as haploview's default view. It was the first prototype of
this bunch of software. Also, it does not keep any pair-wise data
in memory at all, and maybe more suitable where the actual pair-wise
LD data is not needed.
epsout.ld.snp(snpdata, filename, start, end, depth, do.notes=FALSE)epsout.ld.snp(snpdata, filename, start, end, depth, do.notes=FALSE)
snpdata |
An object of |
filename |
The file name of the output, preferably ending with ".eps", but this rule not enforced |
start |
The index of the start of the range of interest. Should be between 1 and (N-1) |
end |
The index of the end of the range of interest. Should be between 2 and N. |
depth |
The depth or lag of pair-wise calculation. Should be between 1 and N-1 |
do.notes |
Boolean for whether to generate pdf annotation-related code |
The functinality of this routine has since been split into a two-stage
processes involving ld.snp which generates a
snp.dprime
object which contains the result of the
pairwise LD calculation, and plot.snp.dprime (or the
plot method of a snp.dprime object) which does the drawing.
return nothing
Hin-Tak Leung [email protected]
Clayton, D.G. and Leung, Hin-Tak (2007) An R package for analysis of
whole-genome association studies.
Human Heredity 64:45-51.
GSL (GNU Scientific Library) http://www.gnu.org/software/gsl/
The postscript language reference manual:
http://www.adobe.com/products/postscript/pdfs/PLRM.pdf
The pdf specification:
http://partners.adobe.com/public/developer/en/pdf/PDFReference16.pdf
snp.dprime-class, ld.snp,
plot.snp.dprime
# data(testdata) epsout.ld.snp(Autosomes, start=1, end=500, depth=50, filename="test.eps")# data(testdata) epsout.ld.snp(Autosomes, start=1, end=500, depth=50, filename="test.eps")
These data have been created artificially from publicly available datasets. The SNPs have been selected from those genotyped by the International HapMap Project (http://www.hapmap.org) to represent the typical density found on a whole genome association chip, (the Affymetrix 500K platform, http://www.affymetrix.com/support/technical/sample\_data/500k\_hapmap\_genotype\_data.affx for a moderately sized chromosome (chromosome 10). A study of 500 cases and 500 controls has been simulated allowing for recombination using beta software from Su and Marchini (http://www.stats.ox.ac.uk/~marchini/software/gwas/hapgen.html). Re-sampling of cases was weighted in such a way as to simulate three “causal” locus on this chromosome, with multiplicative effects of 1.3, 1.4 and 1.5 for each copy of the risk allele.
data(for.exercise)data(for.exercise)
There are three data objects in the dataset:
snps.10
An object of class "snp.matrix"
containing a matrix of SNP genotype calls. Rows of the matrix
correspond to subjects and columns correspond to SNPs.
snp.support
A conventional R
data frame containing information about the
SNPs typed (the chromosome position and the nucleotides
corresponding to the two alleles of the SNP).
subject.support
A conventional R dataframe containing information about the study
subjects. There are two variables; cc gives case/control
status (1=case), and stratum gives ethnicity.
The data were obtained from the diabetes and inflammation laboratory (see http://www-gene.cimr.cam.ac.uk/todd)
http://www-gene.cimr.cam.ac.uk/clayton
data(for.exercise) snps.10 summary(summary(snps.10)) summary(snp.support) summary(subject.support)data(for.exercise) snps.10 summary(summary(snps.10)) summary(snp.support) summary(subject.support)
To carry out a score test for a GLM, we first fit a "base" model using the standard iteratively reweighted least squares (IRLS) algorithm and then carry out a score test for addition of further terms. This function sets various control parameters for this.
glm.test.control(maxit, epsilon, R2Max)glm.test.control(maxit, epsilon, R2Max)
maxit |
Maximum number of IRLS steps |
epsilon |
Convergence threshold for IRLS algorithm |
R2Max |
R-squared limit for aliasing of new terms |
Sometimes (although not always), an iterative scheme is necessary to fit
the "base" generalized linear model (GLM) before carrying out a score
test for effect of adding new term(s). The maxit parameter sets
the maximum number of iterations to be carried out, while the
epsilon parameter sets the criterion for determining
convergence. After fitting the base model, the new terms are added, but
terms judged to be "aliased" are omitted. The method for determining
aliasing is as follows (denoting the "design" matrix for the additional
terms by Z):
Step 1Regress each column of Z on the base model matrix,
using the final GLM weights from the base model fit, and replace
Z with the residuals from these regressions.
Step 2Consider each column of the new Z matrix in turn,
regressing it on the previous columns (again using the weights
from the base model fit). If the proportion of the weighted sum of
squares "explained" by this regression exceeds R2Max, the term
is dropped and not included in the test,
The aim of this procedure to avoid wasting degrees of freedom on columns so strongly aliased that there is little power to detect their effect.
Returns the parameters as a list in the expected order
David Clayton [email protected]
Given a snp.matrix-class or a X.snp.matrix-class object with $N$ samples, calculates some statistics about the relatedness of every pair of samples within.
ibs.stats(x)ibs.stats(x)
x |
a snp.matrix-class or a X.snp.matrix-class object containing $N$ samples |
No-calls are excluded from consideration here.
A data.frame containing $N (N-1)/2$ rows, where the row names are the sample name pairs separated by a comma, and the columns are:
Count |
count of identical calls, exclusing no-calls |
Fraction |
fraction of identical calls comparied to actual calls being made in both samples |
In some applications, it may be preferable to subset a (random) selection of SNPs first - the calculation time increases as $N (N-1) M /2$ . Typically for N = 800 samples and M = 3000 SNPs, the calculation time is about 1 minute. A full GWA scan could take hours, and quite unnecessary for simple applications such as checking for duplicate or related samples.
This is mostly written to find mislabelled and/or duplicate samples.
Illumina indexes their SNPs in alphabetical order so the mitochondria SNPs comes first - for most purpose it is undesirable to use these SNPs for IBS purposes.
TODO: Worst-case S4 subsetting seems to make 2 copies of a large object, so one might want to subset before rbind(), etc; a future version of this routine may contain a built-in subsetting facility to work around that limitation.
Hin-Tak Leung [email protected]
data(testdata) result <- ibs.stats(Autosomes[11:20,]) summary(result)data(testdata) result <- ibs.stats(Autosomes[11:20,]) summary(result)
This function counts, for all pairs of subjects and across all SNPs, the total number of alleles which are identical by state (IBS)
ibsCount(snps)ibsCount(snps)
snps |
An input object of class |
For each pair of subjects the function counts the total number of alleles which are IBS. For autosomal SNPs, each locus contributes 4 comparisons, since each subject carries two copies. For SNPs on the X chromosome, the number of comparisons is also 4 for female:female comparisons, but is 2 for female:male and 1 for male:male comparisons.
If there are N rows in the input matrix, the function returns an N*N matrix. The upper triangle contains the total number of comparisons and the lower triangle contains the number of these which are IBS. The diagonal contains the number of valid calls for each subject.
In genome-wide studies, the SNP data will usually be held as a series of
objects (of
class "snp.matrix" or "X.snp.matrix"), one
per chromosome. Note that the matrices
produced by applying the ibsCount function to each object in turn
can be added to yield the genome-wide result.
David Clayton [email protected]
ibsDist which calculates a distance matrix based
on proportion of alleles which are IBS
data(testdata) ibs.A <- ibsCount(Autosomes[,1:100]) ibs.X <- ibsCount(Xchromosome)data(testdata) ibs.A <- ibsCount(Autosomes[,1:100]) ibs.X <- ibsCount(Xchromosome)
Expresses a matrix of IBS counts (see ibsCount) as a
distance matrix. The distance between two samples is returned as the
proportion of allele comparisons which are not IBS.
ibsDist(counts)ibsDist(counts)
counts |
A matrix of IBS counts as produced by the function
|
An object of class "dist" (see dist)
David Clayton [email protected]
data(testdata) ibs <- ibsCount(Xchromosome) distance <- ibsDist(ibs)data(testdata) ibs <- ibsCount(Xchromosome) distance <- ibsDist(ibs)
ld.snp takes an object of snp.matrix class and suitable
range and depth and calculation the pairwise D', $r^2$, LOD and return
the result as a snp.dprime object.
ld.snp(snpdata, depth = 100, start = 1, end = dim(snpdata)[2], signed.r=FALSE)ld.snp(snpdata, depth = 100, start = 1, end = dim(snpdata)[2], signed.r=FALSE)
snpdata |
An object of |
depth |
The depth or lag of pair-wise calculation. Should be between 1 and N-1; default 100. Using 0 (an invalid value) is the same as picking the maximum |
start |
The index of the start of the range of interest. Should be between 1 and (N-1); default 1 |
end |
The index of the end of the range of interest. Should be between 2 and N. default N. |
signed.r |
Boolean for whether to returned signed $r$ values instead of $r^2$ |
The cubic equation and quadratic equation solver code is borrowed from GSL (GNU Scientific Library).
return a snp.dprime
object, which is a list of 3 named
matrices dprime, rsq2 (or r depending on the input), lod, and an attribute
snp.names for the list of snps involved. (Note that if $x$ snps
are involved, the row numbers of the 3 matrices are $(x-1)$).
Only one of rsq2 or r is present.
dprime |
D' |
rsq2 |
$r^2$ |
r |
signed $r$ |
lod |
Log of Odd's |
All the matrices are defined such that the ($n, m$)th entry is the pair-wise value between the ($n$)th snp and the $(n+m)$th snp. Hence the lower right triangles are always filled with zeros. (See example section for the actual layout)
Invalid values are represented by an out-of-range value - currently we use -1 for D', $r^2$ (both of which are between 0 and 1), and -2 for $r$ (valid values are between -1 and +1). lod is set to zero in most of these invalid cases. (lod can be any value so it is not indicative).
The output snp.dprime object is suitable
for input to plot.snp.dprime for drawing.
The speed of “ld.snp” LD calculation, on a single-processor opteron 2.2GHz box:
unsigned $r^2$, 13191 snps, depth 100 = 36.4 s (~ 1.3 mil pairs)
signed r , 13191 snps, depth 100 = 40.94s (~ 1.3 mil pairs)
signed r , 13191 snps, depth 1500 = 582s (~ 18.5 mil pairs)
For depth=1500, it uses 500MB just for the three matrices. So I actually cannot do the full depth at ~13,000; full depth should be under 50 minutes for 87 mil pairs, even in the signed-r version.
The LD code can be ran outside of R - mainly for debugging:
gcc -DWITHOUT_R -o /tmp/hello pairwise_linkage.c solve_cubic.c \
solve_quadratic.c -lm
When used in this form, it takes 9 numbers:
$/tmp/hello 4 0 0 0 30 0 0 0 23 case 3 <- internal code for which cases it falls in root count 1 <- how many roots trying 1.000000 p = 1.000000 4 0 0 6.333333 0.000000 0.000000 0 30 0 0.000000 25.333333 0.000000 0 0 23 0.000000 0.000000 25.333333 57 8 38.000000 38 38 8 0 0 46 30, 38 38 76 76 0.333333 0.000000 0.000000 0.666667 d' = 1.000000 , r2 = 1.000000, lod= 22.482643
Hin-Tak Leung [email protected]
Clayton, D.G. and Leung, Hin-Tak (2007) An R package for analysis of
whole-genome association studies.
Human Heredity 64:45-51.
GSL (GNU Scientific Library) http://www.gnu.org/software/gsl/
snp.dprime-class,
plot.snp.dprime, ld.with
# LD stats between 500 SNPs at a depth of 50 data(testdata) ldinfo <- ld.snp(Autosomes, start=1, end=500, depth=50)# LD stats between 500 SNPs at a depth of 50 data(testdata) ldinfo <- ld.snp(Autosomes, start=1, end=500, depth=50)
This function calculates the LD measures ($r^2$, D', LOD) of specific SNPs against other SNPs.
ld.with(data, snps, include.itself = as.logical(length(snps) - 1), signed.r = NULL)ld.with(data, snps, include.itself = as.logical(length(snps) - 1), signed.r = NULL)
data |
either a |
snps |
A list of snps, some of which are found in |
include.itself |
Whether to include LD measures of SNPs against itself - it is FALSE for one SNP, since in that case, the result is known and trivial; but otherwise TRUE |
signed.r |
Logical, whether to output signed r or $r^2$ |
Not all combinations of the include.itself and signed.r
make sense, nor fully operational.
The returned value is somewhat similiar to a
snp.dprime
object, but not the same. It is a list of 3 named
matrices dprime, rsq2 (or r depending
on the input), lod.
Because this is really two functions rolled into one, depending on the
class of data, not all combinations of the
include.itself and signed.r make sense, nor fully operational.
Also, the two versions have slightly different idea about invalid values, e.g. the LOD value for a SNPs against itself, or $r^2$ for two monomorphic snps (such as one against itself).
The ld.with function started its life as an extractor
function to take the output of ld.snp, a
snp.dprime-class object, to rearrange it
in a more convenient form to focus on the LD's against specific SNPs,
but then evolved to take a snp.matrix-class object
alternatively and perform the same task directly and more efficiently.
Hin-Tak Leung [email protected]
data(testdata) snps10 <- Autosomes[1:10,1:10] obj.snp.dprime <- ld.snp(snps10) # result1 and result2 should be almost identical # except where noted in the warning section above: result1 <- ld.with(obj.snp.dprime, colnames(snps10)) result2 <- ld.with(snps10, colnames(snps10))data(testdata) snps10 <- Autosomes[1:10,1:10] obj.snp.dprime <- ld.snp(snps10) # result1 and result2 should be almost identical # except where noted in the warning section above: result1 <- ld.with(obj.snp.dprime, colnames(snps10)) result2 <- ld.with(snps10, colnames(snps10))
pair.result.ld.snp.Rd calculates the pairwise D', $r^2$, LOD of
a pair of specified SNPs in a snp.matrix object. This is used
mainly for debugging.
pair.result.ld.snp(snpdata, loc.snpA, loc.snpB)pair.result.ld.snp(snpdata, loc.snpA, loc.snpB)
snpdata |
An object of |
loc.snpA |
index of the first snp; should be between 1 and N |
loc.snpB |
index of the second snp; should be between 1 and N |
Returns nothing. Results are displayed in stdout/console.
Not really recommended for daily usage; the result isn't saved anywhere and this routine is primarily for debugging the details and correctness of the calculation.
Hin-Tak Leung [email protected]
Clayton, D.G. and Leung, Hin-Tak (2007) An R package for analysis of
whole-genome association studies.
Human Heredity 64:45-51.
GSL (GNU Scientific Library) http://www.gnu.org/software/gsl/
data(testdata) pair.result.ld.snp(Autosomes, 1, 2)data(testdata) pair.result.ld.snp(Autosomes, 1, 2)
plot.snp.dprime takes a
snp.dprime object and
draw an eps file to visualize the pairwise D', $r^2$ and LOD.
## S3 method for class 'snp.dprime' plot(x, filename, scheme = "standard", do.notes = FALSE, metric=NULL, ...)## S3 method for class 'snp.dprime' plot(x, filename, scheme = "standard", do.notes = FALSE, metric=NULL, ...)
x |
An object of class |
filename |
The output file name, preferably ending with ".eps" (not enforced) |
scheme |
The colour scheme used. Valid values are "standard" for the Haploview default, and "rsq" for grayscale $r^2$. More may come later |
do.notes |
Boolean for whether to generate pdf annotation-related code |
metric |
An integer vector, detailing the chromosome position of the SNP, to drawa scaled metric of the location of the SNP. If NULL, no metric would be drawn |
... |
place holder |
Annotation is a little used pdf features where certain part of a pdf file are hot spots where one can get pop-up balloons containing extra information, which doesn't appear in print. This is written to imitate the extra information one can get from right-clicking in Haploview's GUI.
return nothing. Write a file as a result. And if do.notes is
specified, Will also suggest user to execute ps2pdf -dEPSCrop
<filename> to get a suitable pdf.
Unfortunately, there are two problems with annotations: only Acrobat Reader (out of all the pdf viewers, e.g. xpdf, kpdf, evince, various ghostscript based viewers) implements the feature, and a few thousand annotations can really make Acrobat Reader crawl.
Also, Acrobat Reader has an implementation limit of 200 inches of the widest dimension of a document. This translates to 1200 snps in the current implementation of the drawing code, hence a warning is emitted that pdf written this way is not viewable by Acrobat Reader.(but viewable by xpdf, etc). A work around is possible based on LaTeX pdfpage, or eps can be included with scaling in another document, to stay inside 200 inches.
In the future, one might want to put some additional scaling code to fit the whole drawing within an A4, for example.
There is a Google Summer of code http://code.google.com/soc/ 2006 project to improve kpdf's annotation support. http://wiki.kde.org/tiki-index.php?page=KDE%20Google%20SoC%202006%20ideas#id60851 I am involved.
Hin-Tak Leung [email protected]
Clayton, D.G. and Leung, Hin-Tak (2007) An R package for analysis of
whole-genome association studies.
Human Heredity 64:45-51.
GSL (GNU Scientific Library) http://www.gnu.org/software/gsl/
The postscript language reference manual:
http://www.adobe.com/products/postscript/pdfs/PLRM.pdf
The pdf specification:
http://partners.adobe.com/public/developer/en/pdf/PDFReference16.pdf
data(testdata) # As for ld.snp example ... data(testdata) ldinfo <- ld.snp(Autosomes, start=1, end=500, depth=50) # Now plot to an eps file plot.snp.dprime(ldinfo, filename="test.eps")data(testdata) # As for ld.snp example ... data(testdata) ldinfo <- ld.snp(Autosomes, start=1, end=500, depth=50) # Now plot to an eps file plot.snp.dprime(ldinfo, filename="test.eps")
This function plots ranked observed chi-squared test statistics against the corresponding expected order statistics. It also estimates an inflation (or deflation) factor, lambda, by the ratio of the trimmed means of observed and expected values. This is useful for inspecting the results of whole-genome association studies for overdispersion due to population substructure and other sources of bias or confounding.
qq.chisq(x, df=1, x.max, main="QQ plot", sub=paste("Expected distribution: chi-squared (",df," df)", sep=""), xlab="Expected", ylab="Observed", conc=c(0.025, 0.975), overdisp=FALSE, trim=0.5, slope.one=FALSE, slope.lambda=FALSE, thin=c(0.25,50), oor.pch=24, col.shade="gray", ...)qq.chisq(x, df=1, x.max, main="QQ plot", sub=paste("Expected distribution: chi-squared (",df," df)", sep=""), xlab="Expected", ylab="Observed", conc=c(0.025, 0.975), overdisp=FALSE, trim=0.5, slope.one=FALSE, slope.lambda=FALSE, thin=c(0.25,50), oor.pch=24, col.shade="gray", ...)
x |
A vector of observed chi-squared test values |
df |
The degreees of freedom for the tests |
x.max |
If present, truncate the observed value (Y) axis here |
main |
The main heading |
sub |
The subheading |
xlab |
x-axis label (default "Expected") |
ylab |
y-axis label (default "Observed") |
conc |
Lower and upper probability bounds for concentration band
for the plot. Set this to |
overdisp |
If |
trim |
Quantile point for trimmed mean calculations for estimation of lambda. Default is to trim at the median |
slope.one |
Is a line of slope one to be superimpsed? |
slope.lambda |
Is a line of slope lambda to be superimposed? |
thin |
A pair of numbers indicating how points will be thinned
before plotting (see Details).
If |
oor.pch |
Observed values greater than |
col.shade |
The colour with which the concentration band will be filled |
... |
Further graphical parameter settings to be passed to
|
To reduce plotting time and the size of plot files, the smallest
observed and expected points are thinned so that only a reduced number of
(approximately equally spaced) points are plotted. The precise
behaviour is controlled by the parameter
thin, whose value should be a pair of numbers.
The first number must lie
between 0 and 1 and sets the proportion of the X axis over which
thinning is to be applied. The second number should be an integer and
sets the maximum number of points to be plotted in this section.
The "concentration band" for the plot is shown in grey. This region is defined by upper and lower probability bounds for each order statistic. The default is to use the 2.5 Note that this is not a simultaneous confidence region; the probability that the plot will stray outside the band at some point exceeds 95
When required, he dispersion factor is estimated by the ratio of the observed trimmed mean to its expected value under the chi-squared assumption.
The function returns the number of tests, the number of values omitted
from the plot (greater than x.max), and the estimated
dispersion factor, lambda.
All tests must have the same number of degrees of freedom. If this is not the case, I suggest transforming to p-values and then plotting -2log(p) as chi-squared on 2 df.
David Clayton [email protected]
Devlin, B. and Roeder, K. (1999) Genomic control for association studies. Biometrics, 55:997-1004
single.snp.tests, snp.lhs.tests,
snp.rhs.tests
## See example the single.snp.tests() function## See example the single.snp.tests() function
Given a URL for HapMap genotype data, read.HapMap.data,
download and convert the genotype data into a snp.matrix class
object, and saving snp support infomation into an associated data.frame.
read.HapMap.data(url, verbose=FALSE, save=NULL, ...)read.HapMap.data(url, verbose=FALSE, save=NULL, ...)
url |
URL for HapMap data. Web data is to be specified with prefix "http://", ftp data with prefix "ftp://", and local file as "file://" |
verbose |
Where the dnSNPalleles annotation is ambiguous, output more details information about how/why assignment is made. See Notes below. |
save |
filename to save the download - if unspecified, a temporary file will be created but removed afterwards. |
... |
Place-holder for further switches - currently ignored. |
During the conversion, if the dbSNPAlleles entry is exactly of the form "X/Y", where X, Y = A or C or G or T, then it is used directly for assigning allele 1 and allele 2.
However, about 1 in 1000 entries are more complicated e.g. may involving deletion, e.g. "-/A/G" or "-/A/AGT/G/T". Some heuristics are used in such cases, in which the observed genotypes in the specific snp of the current batch are examined in two passes. The first time to see which bases are present, excluding "N".
If more than 2 bases are observed in the batch specified in the url, the routine aborts, but so far this possibility has not arisen in tests. If there is exactly two, then allele 1 and 2 are assigned in alphabatical order (dbSNPAlleles entries seems to be always in dictionary order, so the assignment made should agree with a shorten version of the dbSNPAlleles entry). Likewise, if only "A" or "T" is observed, then we know automatically it is the first (assigned as "A/.") or the last allele (assigned as "./T") of a hypothetical pair, without looking at the dbSNPAlleles entry. For other observed cases of 1 base, the routine goes further and look at the dnSNPAlleles entry and see if it begins with "-/X/" or ends with "/X", as a single base, and compare it with the single base observed to see if it should be allele 1 (same as the beginning, or different from the end) and allele 2 (same as the end, or different from the beginning). If no decision can be made for a particular snp entry, the routine aborts with an appropriate message. (For zero observed bases, assignment is "./.", and of course, all observed genotypes of that snp are therefore converted to the equivalent of NA.)
(This heuristics does not cover all grounds, but practically it seems to work. See Notes below.)
Returns a list containing these two items when successful, otherwise returns NULL:
snp.data |
A |
snp.support |
A data.frame, containing the |
Using both "file://" for url and save duplicates the file.
(i.e. by default, the routine make a copy of the url in any case, but
tidy up afterwards if run without save).
Sometimes the assignment may not be unique e.g. dnSNPAlleles entry "A/C/T" and only "C" is observed - this can be assigned "A/C" or "C/T". (currently it does the former). One needs to be especially careful when joining two sets of snp data and it is imperative to compare the assigment supplementary data to see they are compatible. (e.g. for an "A/C/T" entry, one data set may have "C" only and thus have assignment "A/C" and have all of it assigned Allele 2 homozygotes, whereas another data set contains both "C" and "T" and thus the first set needs to be modified before joining).
A typical run, chromosome 1 for CEU, contains about ~400,000 snps and ~100 samples, and the snp.matrix object is about ~60MB (40 million bytes for snps plus overhead) and similiar for the support data (i.e. ~ 2x), takes about 30 seconds, and at peak memory usage requires ~ 4x . The actual download is ~20MB, which is compressed from ~200MB.
Hin-Tak Leung [email protected]
http://www.hapmap.org/genotypes
## Not run: ## ** Please be aware that the HapMap project generates new builds from ## ** time to time and the build number in the URL changes. > library(snpMatrix) > testurl <- paste0("http://www.hapmap.org/genotypes/latest/fwd_strand/", "non-redundant/genotypes_chr1_CEU_r21_nr_fwd.txt.gz") > result1 <- read.HapMap.data(testurl) > sum1 <- summary(result1$snp.data) > head(sum1[is.finite(sum1$z.HWE),], n=10) Calls Call.rate MAF P.AA P.AB P.BB z.HWE rs1933024 87 0.9666667 0.005747126 0.0000000 0.01149425 0.9885057 0.05391549 rs11497407 89 0.9888889 0.005617978 0.0000000 0.01123596 0.9887640 0.05329933 rs12565286 88 0.9777778 0.056818182 0.0000000 0.11363636 0.8863636 0.56511033 rs11804171 83 0.9222222 0.030120482 0.0000000 0.06024096 0.9397590 0.28293272 rs2977656 90 1.0000000 0.005555556 0.9888889 0.01111111 0.0000000 0.05299907 rs12138618 89 0.9888889 0.050561798 0.0000000 0.10112360 0.8988764 0.50240136 rs3094315 88 0.9777778 0.136363636 0.7272727 0.27272727 0.0000000 1.48118392 rs17160906 89 0.9888889 0.106741573 0.0000000 0.21348315 0.7865169 1.12733108 rs2519016 85 0.9444444 0.047058824 0.0000000 0.09411765 0.9058824 0.45528615 rs12562034 90 1.0000000 0.088888889 0.0000000 0.17777778 0.8222222 0.92554468 ## ** Please be aware that the HapMap project generates new builds from ## ** to time and the build number in the URL changes. ## This URL is broken up into two to fit the width of ## the paper. There is no need in actual usage: > testurl2 <- paste0("http://www.hapmap.org/genotypes/latest/", "fwd_strand/non-redundant/genotypes_chr1_JPT_r21_nr_fwd.txt.gz") > result2 <- read.HapMap.data(testurl2) > head(result2$snp.support) dbSNPalleles Assignment Chromosome Position Strand rs10399749 C/T C/T chr1 45162 + rs2949420 A/T A/T chr1 45257 + rs4030303 A/G A/G chr1 72434 + rs4030300 A/C A/C chr1 72515 + rs3855952 A/G A/G chr1 77689 + rs940550 C/T C/T chr1 78032 + ## End(Not run)## Not run: ## ** Please be aware that the HapMap project generates new builds from ## ** time to time and the build number in the URL changes. > library(snpMatrix) > testurl <- paste0("http://www.hapmap.org/genotypes/latest/fwd_strand/", "non-redundant/genotypes_chr1_CEU_r21_nr_fwd.txt.gz") > result1 <- read.HapMap.data(testurl) > sum1 <- summary(result1$snp.data) > head(sum1[is.finite(sum1$z.HWE),], n=10) Calls Call.rate MAF P.AA P.AB P.BB z.HWE rs1933024 87 0.9666667 0.005747126 0.0000000 0.01149425 0.9885057 0.05391549 rs11497407 89 0.9888889 0.005617978 0.0000000 0.01123596 0.9887640 0.05329933 rs12565286 88 0.9777778 0.056818182 0.0000000 0.11363636 0.8863636 0.56511033 rs11804171 83 0.9222222 0.030120482 0.0000000 0.06024096 0.9397590 0.28293272 rs2977656 90 1.0000000 0.005555556 0.9888889 0.01111111 0.0000000 0.05299907 rs12138618 89 0.9888889 0.050561798 0.0000000 0.10112360 0.8988764 0.50240136 rs3094315 88 0.9777778 0.136363636 0.7272727 0.27272727 0.0000000 1.48118392 rs17160906 89 0.9888889 0.106741573 0.0000000 0.21348315 0.7865169 1.12733108 rs2519016 85 0.9444444 0.047058824 0.0000000 0.09411765 0.9058824 0.45528615 rs12562034 90 1.0000000 0.088888889 0.0000000 0.17777778 0.8222222 0.92554468 ## ** Please be aware that the HapMap project generates new builds from ## ** to time and the build number in the URL changes. ## This URL is broken up into two to fit the width of ## the paper. There is no need in actual usage: > testurl2 <- paste0("http://www.hapmap.org/genotypes/latest/", "fwd_strand/non-redundant/genotypes_chr1_JPT_r21_nr_fwd.txt.gz") > result2 <- read.HapMap.data(testurl2) > head(result2$snp.support) dbSNPalleles Assignment Chromosome Position Strand rs10399749 C/T C/T chr1 45162 + rs2949420 A/T A/T chr1 45257 + rs4030303 A/G A/G chr1 72434 + rs4030300 A/C A/C chr1 72515 + rs3855952 A/G A/G chr1 77689 + rs940550 C/T C/T chr1 78032 + ## End(Not run)
This function read the accompanying info file of a LINKAGE ped file, for the SNP names, position and chromosome.
read.pedfile.info(file)read.pedfile.info(file)
file |
An info file |
One such info file is the one accompanying the sample ped file of Haploview.
A data frame with columns "snp.names", "position", "chromosome".
This is used internally by read.snps.pedfile
to read an accompanying info file.
Hin-Tak Leung [email protected]
See the documentation and description of ped files in Haploview (http://www.broad.mit.edu/mpg/haploview/)
This function read the accompanying map file of a LINKAGE ped file, for the SNP names, position and chromosome.
read.pedfile.map(file)read.pedfile.map(file)
file |
A Plink map file |
One such map file is the one accompanying the sample ped file of Haploview.
A data frame with columns "snp.names", "position", "chromosome".
This is used internally by read.snps.pedfile
to read an accompanying map file.
Hin-Tak Leung [email protected]
See the documentation and description of ped files in Haploview (http://www.broad.mit.edu/mpg/haploview/)
This function reads data from the raw output of Chiamo
read.snps.chiamo(filename, sample.list, threshold)read.snps.chiamo(filename, sample.list, threshold)
filename |
List of file names of output from Chiamo ; the outcome is the concatenation from runs of Chiamo, e.g. on blocks of SNPs, which is often done for practical reasons |
sample.list |
A character vector giving the sample list |
threshold |
Cut-off for the posterior probability for a no-call |
The raw output of Chiamo consists of the first 5 columns of
read.wtccc.signals, followed by triplets of posterior
probabilities of calling A-A, A-B, or B-B.
The sample list can typically be obtained using
wtccc.sample.list, from one of the (smaller) signal
files, which are the inputs to Chiamo.
The result is a list of two items:
snp.data |
The genotype data as a |
snp.support |
The information from the first 5 columns of |
Hin-Tak Leung [email protected]
To obtain a copy of the Chiamo software please email Jonathan L. Marchini <[email protected]>.
wtccc.sample.list, read.wtccc.signals
##
Reads SNP data when organized in free format
as one call per line. Other than the one
call per line requirement, there is considerable flexibility. Multiple
input files can be read, the input fields can be in any order on the
line, and irrelevant fields can be skipped. The samples and SNPs
to be read must be pre-specified, and define rows and columns of an
output object of class "snp.matrix".
read.snps.long(files, sample.id = NULL, snp.id = NULL, female = NULL, fields = c(sample = 1, snp = 2, genotype = 3, confidence = 4), codes = c("0", "1", "2"), threshold = 0.9, lower = TRUE, sep = " ", comment = "#", skip = 0, simplify = c(FALSE,FALSE), verbose = FALSE, every = 1000)read.snps.long(files, sample.id = NULL, snp.id = NULL, female = NULL, fields = c(sample = 1, snp = 2, genotype = 3, confidence = 4), codes = c("0", "1", "2"), threshold = 0.9, lower = TRUE, sep = " ", comment = "#", skip = 0, simplify = c(FALSE,FALSE), verbose = FALSE, every = 1000)
files |
A character vector giving the names of the input files |
sample.id |
A character vector giving the identifiers of the samples to be read |
snp.id |
A character vector giving the names of the SNPs to be read |
female |
If the SNPs are on the X chromosome and the data are to
be read as such, this logical vector (of the same length as
|
fields |
A integer vector with named elements specifying the
positions of the required fields in the input record. The fields are
identified by the names |
codes |
Either the single string |
threshold |
A numerical value for the calling threshold on the confidence score |
lower |
If |
sep |
The delimiting character separating fields in the input record |
comment |
A character denoting that any remaining input on a line is to be ignored |
skip |
An integer value specifying how many lines are to be skipped at the beginning of each data file |
simplify |
If |
verbose |
If |
every |
See |
If nucleotide coding is not used, the codes argument
should be a character array giving the valid codes.
For genotype coding of autosomal SNPs, this should be
an array of length 3 giving the codes
for the three genotypes, in the order homozygous(AA), heterozygous(AB),
homozygous(BB). All other codes will be treated
as "no call". The default codes are "0", "1",
"2". For X SNPs, males are assumed to be coded as homozygous,
unless an additional two codes are supplied (representing the
AY and BY genotypes). For allele coding, the
codes array should be of length 2 and should specify the codes
for the two alleles. Again, any other code is treated as
"missing" and, for X SNPs, males should be coded either as
homozygous or by omission of the second allele.
Although the function allows for reading of data for the X chromosome
directly into an object of class "X.snp.matrix",
it will often be preferable to read such data as a "snp.matrix"
(i.e. as autosomal) and to coerce it to an object of type
"X.snp.matrix" later using as(..., "X.snp.matrix") or
new("X.snp.matrix", ..., female=...).
The vectors sample.id and snp.id must be in the same
order as they vary on the input file(s) and this ordering must be
consistent. However, there is
no requirement that either SNP or sample should vary fastest; this is
detected from the input.
Each file may represent a separate sample or SNP, in which case the
appropriate .id argument can be omitted and row or column names
taken from the file names.
An object of class "snp.matrix" or "X.snp.matrix".
The function will read gzipped files.
This function has replaced and earlier version which was much less
flexible. Because all features have not been fully tested, the older
version has been retained as read.snps.long.old.
David Clayton [email protected]
read.HapMap.dataread.snps.pedfile,
read.snps.chiamo,read.snps.long,
snp.matrix-class, X.snp.matrix-class
This function reads SNP genotype data and creates an object of class
"snp.matrix" or "X.snp.matrix".
Input data are assumed to be arranged as one line per
SNP-call (without any headers). This function can read gzipped files.
read.snps.long.old(file, chip.id, snp.id, codes, female, conf = 1, threshold = 0.9, drop=FALSE, sorted=FALSE, progress=interactive())read.snps.long.old(file, chip.id, snp.id, codes, female, conf = 1, threshold = 0.9, drop=FALSE, sorted=FALSE, progress=interactive())
file |
Name of file containing the input data. Input files
which have been compressed by the |
chip.id |
Array of type |
snp.id |
Array of type |
codes |
For autosomal SNPs, an array of length 3 giving the codes
for the three genotypes, in the order homozygous(AA), heterozygous(AB),
homozygous(BB). For X SNPs, an additional two codes for the male
genotypes (AY and BY) must be supplied. All other codes will be treated
as "no call". The default codes are |
female |
If the data to be read refer to SNPs on the X chromosome, this
argument must be supplied and should indicate whether each row of
data refers to a female ( |
conf |
Confidence score. See details |
drop |
If |
threshold |
Acceptance threshold for confidence score |
sorted |
Is input file already sorted into the correct order (see details)? |
progress |
If |
Data are assumed to be input with one line per call, in free
format:
<chip-id> <snp-id> <code for genotype call>
[<confidence>] ...
Currently, any fields following the first three (or four) are
ignored. If the argument sorted is TRUE, the file is
assumed to be sorted
with snp-id as primary key and
chip-id as secondary key using the current locale. The rows and
columns of the returned matrix will also be ordered in this manner. If
sorted is set to FALSE, then an algorithm which avoids
this assumption is used. The rows and columns of the returned matrix
will then be in the same order as the input chip_id and
snp_id vectors. Calls in which both id fields match elements in the
chip.id and
snp.id arguments are read in, after (optionally) checking that
the level of confidence achieves a given threshold.
Confidence level checking is
controlled by the conf argument. conf=0 indicates that
no confidence score is present and no checking is done. conf>0
indicates that calls with scores above threshold are accepted,
while conf<0 indicates that only calls with scores below
threshold should be accepted.
The routine is case-sensitive and it is important that the
<chip-id> and <snp-id> match the cases of
chip.id and snp.id exactly.
An object of class snp.matrix.
If more than one instance of any
combination of chip_id element and snp_id element
passes the confidence threshold, the called to be used is decided by
the following rules:
1Any call trumps "no-call"
2In the event of call conflict, "no-call" is returned
Use of sorted=TRUE is usually discouraged since the alternative
algorithm is safer and, usually, not appreciably slower. However, if
the input file is to be read multiple times and there is a reasonably
close correspondence between cells of the matrix to be returned and
lines of the input file, the sorted option can be faster.
This function has been replaced by the more flexible function
read.snps.long.
David Clayton [email protected] and Hin-Tak Leung
http://www-gene.cimr.cam.ac.uk/clayton
snp.matrix-class, X.snp.matrix-class
This function reads data arranged as a LINKAGE "pedfile" with some
restrictions and returns a list of three objects: a data frame
containing the initial 6 fields giving pedigree structure, sex and
disease status, a vector or a data frame containing snp assignment
and possibly other snp infomation, and an object of class
"snp.matrix" or "X.snp.matrix" containing the genotype data
read.snps.pedfile(file, snp.names=NULL, assign=NULL, missing=NULL, X=FALSE, sep=".", low.mem = FALSE)read.snps.pedfile(file, snp.names=NULL, assign=NULL, missing=NULL, X=FALSE, sep=".", low.mem = FALSE)
file |
The file name for the input pedfile |
snp.names |
A character vector giving the SNP names. If an accompanying map file or an info file is present, it will be read and the information used for the SNP names, and also the information merged with the result. If absent, the SNPs will be named numerically ("1", "2", ...) |
assign |
A list of named mappings for which letter maps to which Allele; planned for the future, not currently used |
missing |
Meant to be a single character giving the code recorded for alleles of missing genotypes ; not used in the current code |
X |
If |
sep |
The character separating the family and member identifiers in the constructed row names; not used |
low.mem |
Switch over to input with a routine which requires less memory to run, but takes a little longer. This option also has the disadvantage that assignment of A/B genotype is somewhat non-deterministic and depends the listed order of samples. |
Input variables are assumed to take the usual codes, with the restriction that the family (or pedigree) identifiers will be held as strings, but identifiers for members within families must be coded as integers. Genotype should be coded as pairs of single character allele codes (which can be alphameric or numeric), from either 'A', 'C', 'G', 'T' or '1', '2', '3', '4', with 'N', '-' and '0' denoting a missing; everything else is considered invalid and would invalidate the whole snp; also more than 2 alleles also cause the snp to be marked invalid.
Row names of the output objects are constructed by concatenation of the pedigree and member identifiers, "Family", "Individual" joined by ".", e.g. "Family.Adams.Individual.0".
snps |
The output |
subject.support |
A data frame containing the first six fields of the pedfile |
Hin-Tak Leung
snp.matrix-class, X.snp.matrix-class,
read.snps.long, read.HapMap.data,
read.pedfile.info, read.pedfile.map
read.wtccc.signals takes a file and a list of snp ids (either
Affymetrix ProbeSet IDs or rs numbers), and extract the entries
into a form suitable for plotting and further analysis
read.wtccc.signals(file, snp.list)read.wtccc.signals(file, snp.list)
file |
|
snp.list |
A list of snp id's. Some Affymetrix SNPs don't have rsnumbers both rsnumbers and Affymetrix ProbeSet IDs are accepted |
Do not specify both rs number and Affymetrix Probe Set ID in the input; one of them is enough.
The signal file is formatted as follows, with the first 5 columns being the Affymetrix Probe Set ID, rs number, chromosome position, AlleleA and AlleleB. The rest of the header containing the sample id appended with "\_A" and "\_B".
AFFYID RSID pos AlleleA AlleleB 12999A2_A 12999A2_B ... SNP_A-4295769 rs915677 14433758 C T 0.318183 0.002809 SNP_A-1781681 rs9617528 14441016 A G 1.540461 0.468571 SNP_A-1928576 rs11705026 14490036 G T 0.179653 2.261650
The routine matches the input list against the first and the 2nd column.
(some early signal files, have the first "AFFYID" missing - this routine can cope with that also)
The routine returns a list of named matrices, one for each input SNP
(NULL if the SNP is not found); the row names are sample IDs
and columns are "A", "B" signals.
TODO: There is a built-in limit to the input line buffer (65535) which should be sufficient for 2000 samples and 30 characters each. May want to seek backwards, re-read and dynamically expand if the buffer is too small.
Hin-Tak Leung [email protected]
## Not run: answer <- read.wtccc.signals("NBS_22_signals.txt.gz", c("SNP_A-4284341","rs4239845")) > summary(answer) Length Class Mode SNP_A-4284341 2970 -none- numeric rs4239845 2970 -none- numeric > head(a$"SNP_A-4284341") A B 12999A2 1.446261 0.831480 12999A3 1.500956 0.551987 12999A4 1.283652 0.722847 12999A5 1.549140 0.604957 12999A6 1.213645 0.966151 12999A8 1.439892 0.509547 > ## End(Not run)## Not run: answer <- read.wtccc.signals("NBS_22_signals.txt.gz", c("SNP_A-4284341","rs4239845")) > summary(answer) Length Class Mode SNP_A-4284341 2970 -none- numeric rs4239845 2970 -none- numeric > head(a$"SNP_A-4284341") A B 12999A2 1.446261 0.831480 12999A3 1.500956 0.551987 12999A4 1.283652 0.722847 12999A5 1.549140 0.604957 12999A6 1.213645 0.966151 12999A8 1.439892 0.509547 > ## End(Not run)
This function calculates call rates and heterozygosity for each row of a an
object of class "snp.matrix"
row.summary(object)row.summary(object)
object |
genotype data as a |
A data frame with rows corresponding to rows of the input object and with columns/elements:
Call.rate |
Proportion of SNPs called |
Heterozygosity |
Proportion of called SNPs which are heterozygous |
The current version does not deal with the X chromosome differently, so that males are counted as homozygous
David Clayton [email protected]
data(testdata) rs <- row.summary(Autosomes) summary(rs) rs <- row.summary(Xchromosome) summary(rs)data(testdata) rs <- row.summary(Autosomes) summary(rs) rs <- row.summary(Xchromosome) summary(rs)
This function carries out tests for association between phenotype and a series of single nucleotide polymorphisms (SNPs), within strata defined by a possibly confounding factor. SNPs are considered one at a time and both 1-df and 2-df tests are calculated. For a binary phenotype, the 1-df test is the Cochran-Armitage test (or, when stratified, the Mantel-extension test).
single.snp.tests(phenotype, stratum, data = sys.parent(), snp.data, subset, snp.subset)single.snp.tests(phenotype, stratum, data = sys.parent(), snp.data, subset, snp.subset)
phenotype |
A vector containing the values of the phenotype |
stratum |
Optionally, a factor defining strata for the analysis |
data |
A dataframe containing the |
snp.data |
An object of class |
subset |
A vector or expression describing the subset of subjects
to be used in teh analysis. This is evaluated in the same
environment as the |
snp.subset |
A vector describing the subset of SNPs to be considered. Default action is to test all SNPs. |
Formally, the test statistics are score tests for generalized linear models with canonical link. That is, they are inner products between genotype indicators and the deviations of phenotypes from their stratum means. Variances (and covariances) are those of the permutation distribution obtained by randomly permuting phenotype within stratum.
The subset argument can either be a logical vector of length
equal to the length of the vector of phenotypes, an integer vector
specifying positions in the data frame, or a character vector
containing names of the selected rows in the data
frame. Similarly, the snp.subset argument can be a logical,
integer, or character vector.
A dataframe, with columns
chi2.1df |
Cochran-Armitage type test for additive genetic component |
chi2.2df |
Chi-squared test for both additive and dominance components |
N |
The number of valid data points used |
The behaviour of this function for objects of class
X.snp.matrix is as described by Clayton (2008). Males are
treated as homozygous females and corrected variance estimates are
used.
David Clayton [email protected]
Clayton (2008) Testing for association on the X chromosome Biostatistics (In press)
data(testdata) results <- single.snp.tests(cc, stratum=region, data=subject.data, snp.data=Autosomes, snp.subset=1:10) summary(results) # QQ plot - see help(qq.chisq) qq.chisq(results$chi2.1df) qq.chisq(results$chi2.2df)data(testdata) results <- single.snp.tests(cc, stratum=region, data=subject.data, snp.data=Autosomes, snp.subset=1:10) summary(results) # QQ plot - see help(qq.chisq) qq.chisq(results$chi2.1df) qq.chisq(results$chi2.2df)
Compact representation of data concerning single nucleotide polymorphisms (SNPs)
Objects can be created by calls of the form new("snp", ...) or
by subset selection from an object of class "snp.matrix".
Holds one row or column of an object of class "snp.matrix"
.Data:The genotype data coded as 0, 1, 2, or 3
signature(from = "snp", to =
"character"): map to codes "A/A", "A/B", "B/B", or ""
signature(from = "snp", to = "numeric"):
map to codes 0, 1, 2, or NA
signature(from = "snp", to = "genotype"): maps
a single SNP to an object of class "genotype". See
the "genetics" package
.
signature(object = "snp"): shows character
representation of the object
signature(x = "snp"): returns a logical
vector of missing call indicators
David Clayton [email protected]
http://www-gene.cimr.cam.ac.uk/clayton
snp.matrix-class,
X.snp.matrix-class, X.snp-class
## data(testdata) ## s <- autosomes[,1] ## class(s) ## s## data(testdata) ## s <- autosomes[,1] ## class(s) ## s
These functions bind together two or more objects of class
"snp.matrix" or "X.snp.matrix".
snp.cbind(...) snp.rbind(...)snp.cbind(...) snp.rbind(...)
... |
Objects of class |
These functions reproduce the action of the standard functions
cbind and rbind. These are constrained to
work by recursive calls to the generic functions cbind2
and rbind2 which take just two arguments. This
is somewhat inefficient in both time and memory use when binding more
than two objects, so the functions snp.cbind and
snp.rbind, which take multiple arguments, are also supplied.
When matrices are bound together by column, row names must be identical,
column names must not be duplicated and, for objects of class
X.snp.matrix the contents of the Female slot much match.
When matrices are bound by row,
column names must be identical. and duplications of row names generate
warnings.
A new matrix, of the same type as the input matrices.
David Clayton [email protected]
data(testdata) # subsetting ( Autosomes[c(1:9,11:19,21:29),] ) is quicker. this is just for illustrating # rbind and cbind first <- Autosomes[1:9,] second <- Autosomes[11:19,] third <- Autosomes[21:29,] result1 <- rbind(first, second, third) result2 <- snp.rbind(first, second, third) all.equal(result1, result2) result3 <- Autosomes[c(1:9,11:19,21:29),] all.equal(result1, result3) first <- Autosomes[,1:9] second <- Autosomes[,11:19] third <- Autosomes[,21:29] result1 <- cbind(first, second, third) result2 <- snp.cbind(first, second, third) all.equal(result1, result2) result3 <- Autosomes[,c(1:9,11:19,21:29)] all.equal(result1, result3) first <- Xchromosome[1:9,] second <- Xchromosome[11:19,] third <- Xchromosome[21:29,] result1 <- rbind(first, second, third) result2 <- snp.rbind(first, second, third) all.equal(result1, result2) result3 <- Xchromosome[c(1:9,11:19,21:29),] all.equal(result1, result3) first <- Xchromosome[,1:9] second <- Xchromosome[,11:19] third <- Xchromosome[,21:29] result1 <- cbind(first, second, third) result2 <- snp.cbind(first, second, third) all.equal(result1, result2) result3 <- Xchromosome[,c(1:9,11:19,21:29)] all.equal(result1, result3)data(testdata) # subsetting ( Autosomes[c(1:9,11:19,21:29),] ) is quicker. this is just for illustrating # rbind and cbind first <- Autosomes[1:9,] second <- Autosomes[11:19,] third <- Autosomes[21:29,] result1 <- rbind(first, second, third) result2 <- snp.rbind(first, second, third) all.equal(result1, result2) result3 <- Autosomes[c(1:9,11:19,21:29),] all.equal(result1, result3) first <- Autosomes[,1:9] second <- Autosomes[,11:19] third <- Autosomes[,21:29] result1 <- cbind(first, second, third) result2 <- snp.cbind(first, second, third) all.equal(result1, result2) result3 <- Autosomes[,c(1:9,11:19,21:29)] all.equal(result1, result3) first <- Xchromosome[1:9,] second <- Xchromosome[11:19,] third <- Xchromosome[21:29,] result1 <- rbind(first, second, third) result2 <- snp.rbind(first, second, third) all.equal(result1, result2) result3 <- Xchromosome[c(1:9,11:19,21:29),] all.equal(result1, result3) first <- Xchromosome[,1:9] second <- Xchromosome[,11:19] third <- Xchromosome[,21:29] result1 <- cbind(first, second, third) result2 <- snp.cbind(first, second, third) all.equal(result1, result2) result3 <- Xchromosome[,c(1:9,11:19,21:29)] all.equal(result1, result3)
This function calculates Pearson correlation coefficients between columns of a
snp.matrix and columns of an ordinary matrix. The two matrices
must have the same number of rows. All valid pairs are used in the
computation of each correlation coefficient.
snp.cor(x, y)snp.cor(x, y)
x |
An N by M |
y |
An N by P general matrix |
This can be used together with xxt and
eigen to calculate standardized loadings in the principal
components
An M by P matrix of correlation coefficients
This version cannot handle X chromosomes
David Clayton [email protected]
# make a snp.matrix with a small number of rows data(testdata) small <- Autosomes[1:100,] # Calculate the X.X-transpose matrix xx <- xxt(small, correct.for.missing=TRUE) # Calculate the principal components pc <- eigen(xx, symmetric=TRUE)$vectors # Calculate the loadings in first 10 components, # for eaxample to plot against chromosome position loadings <- snp.cor(small, pc[,1:10])# make a snp.matrix with a small number of rows data(testdata) small <- Autosomes[1:100,] # Calculate the X.X-transpose matrix xx <- xxt(small, correct.for.missing=TRUE) # Calculate the principal components pc <- eigen(xx, symmetric=TRUE)$vectors # Calculate the loadings in first 10 components, # for eaxample to plot against chromosome position loadings <- snp.cor(small, pc[,1:10])
The snp.dprime class encapsulates results returned by
ld.snp (— routine to calculate D', $r^2$ and LOD of a
snp.matrix-class object, given
a range and a depth) and is based on a list of three
named matrices.
The lower right triangle of the snp.dprime object returned by ld.snp
always consists zeros. This is delibrate. The associated plotting routine
would not normally access those elements either.
The snp.dprime class is a list of 3 named
matrices dprime, rsq2 or r, lod, and an attribute
snp.names for the list of snps involved. (Note that if $x$ snps
are involved, the row numbers of the 3 matrices are $(x-1)$).
Only one of r or rsq2 is present.
dprime |
D' |
rsq2 |
$r^2$ |
r |
signed $r^2$ |
lod |
Log of Odd's |
attr(*, class)
|
"snp.dprime" |
attr(*, snp.names)
|
character vectors of the snp names involved |
All the matrices are defined such that the ($n, m$)th entry is the pair-wise value between the ($n$)th snp and the $(n+m)$th snp. Hence the lower right triangles are always filled with zeros.
Invalid values are represented by an out-of-range value - currently we use -1 for D', $r^2$ (both of which are between 0 and 1), and -2 for $r$ (valid values are between -1 and +1). lod is set to zero in most of these invalid cases. (lod can be any value so it is not indicative).
See plot.snp.dprime.
TODO: Need a subsetting operator.
TODO: an assemble operator
Hin-Tak Leung [email protected]
~~ reference to a publication or URL from which the data were obtained ~~
~~ possibly secondary sources and usages ~~
data(testdata) snps20.20 <- Autosomes[11:20,11:20] obj.snp.dprime <- ld.snp(snps20.20) class(obj.snp.dprime) summary(obj.snp.dprime) ## Not run: # The following isn't executable-as-is example, so these illustrations # are commented out to stop R CMD check from complaining: > d<- ld.snp(all, 3, 10, 15) rows = 48, cols = 132 ... Done > d $dprime [,1] [,2] [,3] [1,] 1 1 1 [2,] 1 1 1 [3,] 1 1 1 [4,] 1 1 0 [5,] 1 0 0 $rsq2 [,1] [,2] [,3] [1,] 1.0000000 0.9323467 1.0000000 [2,] 0.9285714 1.0000000 0.1540670 [3,] 0.9357278 0.1854481 0.9357278 [4,] 0.1694915 1.0000000 0.0000000 [5,] 0.1694915 0.0000000 0.0000000 $lod [,1] [,2] [,3] [1,] 16.793677 11.909686 16.407120 [2,] 10.625650 15.117962 2.042668 [3,] 12.589586 2.144780 12.589586 [4,] 2.706318 16.781859 0.000000 [5,] 2.706318 0.000000 0.000000 attr(,"class") [1] "snp.dprime" attr(,"snp.names") [1] "dil118" "dil119" "dil5904" "dil121" "dil5905" "dil5906" ## End(Not run)data(testdata) snps20.20 <- Autosomes[11:20,11:20] obj.snp.dprime <- ld.snp(snps20.20) class(obj.snp.dprime) summary(obj.snp.dprime) ## Not run: # The following isn't executable-as-is example, so these illustrations # are commented out to stop R CMD check from complaining: > d<- ld.snp(all, 3, 10, 15) rows = 48, cols = 132 ... Done > d $dprime [,1] [,2] [,3] [1,] 1 1 1 [2,] 1 1 1 [3,] 1 1 1 [4,] 1 1 0 [5,] 1 0 0 $rsq2 [,1] [,2] [,3] [1,] 1.0000000 0.9323467 1.0000000 [2,] 0.9285714 1.0000000 0.1540670 [3,] 0.9357278 0.1854481 0.9357278 [4,] 0.1694915 1.0000000 0.0000000 [5,] 0.1694915 0.0000000 0.0000000 $lod [,1] [,2] [,3] [1,] 16.793677 11.909686 16.407120 [2,] 10.625650 15.117962 2.042668 [3,] 12.589586 2.144780 12.589586 [4,] 2.706318 16.781859 0.000000 [5,] 2.706318 0.000000 0.000000 attr(,"class") [1] "snp.dprime" attr(,"snp.names") [1] "dil118" "dil119" "dil5904" "dil121" "dil5905" "dil5906" ## End(Not run)
Under the assumption of Hardy-Weinberg equilibrium, a SNP genotype is
a binomial variate with two trials for an autosomal SNP or with one or
two trials (depending on sex) for a SNP on the X chromosome.
With each SNP in an input
"snp.matrix" as dependent variable, this function first fits a
"base" logistic regression model and then carries out a score test for
the addition of further term(s). The Hardy-Weinberg
assumption can be relaxed by use of a "robust" option.
snp.lhs.tests(snp.data, base.formula, add.formula, subset, snp.subset, data = sys.parent(), robust = FALSE, control=glm.test.control(maxit=20, epsilon=1.e-4, R2Max=0.98))snp.lhs.tests(snp.data, base.formula, add.formula, subset, snp.subset, data = sys.parent(), robust = FALSE, control=glm.test.control(maxit=20, epsilon=1.e-4, R2Max=0.98))
snp.data |
The SNP data, as an object of class
|
base.formula |
A |
add.formula |
A |
subset |
An array describing the subset of observations to be considered |
snp.subset |
An array describing the subset of SNPs to be considered. Default action is to test all SNPs. |
data |
The data frame in which |
robust |
If |
control |
An object giving parameters for the IRLS algorithm fitting of the base model and for the acceptable aliasing amongst new terms to be tested. See\ codeglm.test.control |
The tests used are asymptotic chi-squared tests based on the vector of
first and second derivatives of the log-likelihood with respect to the
parameters of the additional model. The "robust" form is a generalized
score test in the sense discussed by Boos(1992).
If a data argument is supplied, the snp.data and
data objects are aligned by rowname. Otherwise all variables in
the model formulae are assumed to be stored in the same order as the
columns of the snp.data object.
A data frame containing, for each SNP,
Chi.squared |
The value of the chi-squared test statistic |
Df |
The corresponding degrees of freedom |
Df.residual |
The residual degrees of freedom for the base model; i.e. the number of observations minus the number of parameters fitted |
For the logistic model, the base model can, in some circumstances, lead to perfect prediction of some observations (i.e. fitted probabilities of 0 or 1). These observations are ignored in subsequent calculations; in particular they are not counted in the residual degrees of freedom.
A factor (or
several factors) may be included as arguments to the function
strata(...) in the base.formula. This fits all
interactions of the factors so included, but leads to faster
computation than fitting these in the normal way. Additionally, a
cluster(...) call may be included in the base model
formula. This identifies clusters of potentially correlated
observations (e.g. for members of the same family); in this case, an
appropriate robust estimate of the variance of the score test is used.
David Clayton [email protected]
Boos, Dennis D. (1992) On generalized score tests. The American Statistician, 46:327-333.
glm.test.control,snp.rhs.tests
single.snp.tests, snp.matrix-class,
X.snp.matrix-class
data(testdata) library(survival) slt1 <- snp.lhs.tests(Autosomes[,1:10], ~cc, ~region, data=subject.data) print(slt1) slt2 <- snp.lhs.tests(Autosomes[,1:10], ~strata(region), ~cc, data=subject.data) print(slt2)data(testdata) library(survival) slt1 <- snp.lhs.tests(Autosomes[,1:10], ~cc, ~region, data=subject.data) print(slt1) slt2 <- snp.lhs.tests(Autosomes[,1:10], ~strata(region), ~cc, data=subject.data) print(slt2)
This class defines objects holding large arrays of single nucleotide polymorphism (SNP) genotypes generated using array technologies.
Objects can be created by calls of the form new("snp.matrix", x)
where x is a matrix with storage mode "raw".
Chips (usually corresponding to samples or
subjects) define rows of the matrix while polymorphisms (loci) define
columns. Rows and columns will usually have names which can be
used to link the data to further data concerning samples and SNPs
.Data:Object of class "matrix" and storage
mode raw
Internally, missing data are coded 00 and SNP genotypes are coded
01, 02 or 03.
Class "matrix", from data part.
Class "structure", by class "matrix".
Class "array", by class "matrix".
Class "vector", by class "matrix", with explicit coerce.
Class "vector", by class "matrix", with explicit coerce.
signature(x = "snp.matrix"): subset
operations. Currently rather slow owing to excessive copying.
signature(x = "snp.matrix", y = "snp.matrix"):
S4 generic function to provide cbind() for two or
more matrices together by column. Row names must match and column
names must not coincide. If the matrices are of the derived class
X.snp.matrix-class, the Female slot values must also
agree
signature(from = "snp.matrix", to = "numeric"):
map to codes 0, 1, 2, or NA
signature(from = "snp.matrix", to =
"character"): map to codes "A/A", "A/B", "B/B", ""
signature(from = "matrix", to = "snp.matrix"):
maps numeric matrix (coded 0, 1, 2 or NA) to a snp.matrix
signature(from = "snp.matrix", to =
"X.snp.matrix"):
maps a snp.matrix to an X.snp.matrix. Sex is inferred from the
genotype data since males should not be heterozygous at any locus.
After inferring sex, heterozygous calls for males are set to
NA
signature(x = "snp.matrix"): returns a logical
matrix indicating whether each element is NA
signature(x = "snp.matrix", y = "snp.matrix"):
S4 generic function to provide rbind() for two or
more matrices by row. Column names must match and duplicated row
names prompt warnings
signature(object = "snp.matrix"): shows the size
of the matrix (since most objects will be too large to show in full)
signature(object = "snp.matrix"): calculate
call rates, allele frequencies, genotype frequencies, and z-tests for
Hardy-Weinberg equilibrium. Results are returned as a dataframe with
column names Calls, Call.rate, MAF, P.AA,
P.AB, P.BB, and z.HWE
signature(x = "snp.matrix"): returns a logical
matrix of missing call indicators
signature(object = "snp.matrix"): ...
signature(object = "snp.matrix"): ...
This class requires at least version 2.3 of R
David Clayton [email protected]
http://www-gene.cimr.cam.ac.uk/clayton
snp-class, X.snp-class,
X.snp.matrix-class
data(testdata) summary(summary(Autosomes)) # Just making it up - 3-10 will be made into NA during conversion snps.class<-new("snp.matrix", matrix(1:10)) snps.class if(!isS4(snps.class)) stop("constructor is not working") pretend.X <- as(Autosomes, 'X.snp.matrix') if(!isS4(pretend.X)) stop("coersion to derived class is not S4") if(class(pretend.X) != 'X.snp.matrix') stop("coersion to derived class is not working") pretend.A <- as(Xchromosome, 'snp.matrix') if(!isS4(pretend.A)) stop("coersion to base class is not S4") if(class(pretend.A) != 'snp.matrix') stop("coersion to base class is not working")data(testdata) summary(summary(Autosomes)) # Just making it up - 3-10 will be made into NA during conversion snps.class<-new("snp.matrix", matrix(1:10)) snps.class if(!isS4(snps.class)) stop("constructor is not working") pretend.X <- as(Autosomes, 'X.snp.matrix') if(!isS4(pretend.X)) stop("coersion to derived class is not S4") if(class(pretend.X) != 'X.snp.matrix') stop("coersion to derived class is not working") pretend.A <- as(Xchromosome, 'snp.matrix') if(!isS4(pretend.A)) stop("coersion to base class is not S4") if(class(pretend.A) != 'snp.matrix') stop("coersion to base class is not working")
These functions first standardize the input snp.matrix in the
same way as does the function xxt. The standardized
matrix is then either pre-multiplied (snp.pre) or
post-multiplied (snp.post) by a general matrix. Allele
frequencies for standardizing the input snp.matrix may be supplied
but, otherwise, are calculated from the input snp.matrix
snp.pre(snps, mat, frequency=NULL) snp.post(snps, mat, frequency=NULL)snp.pre(snps, mat, frequency=NULL) snp.post(snps, mat, frequency=NULL)
snps |
An object of class |
mat |
A general (numeric) matrix |
frequency |
A numeric vector giving the allele (relative)
frequencies to be used for standardizing the columns of |
The two matrices must be conformant, as with standard matrix multiplication. The main use envisaged for these functions is the calculation of factor loadings in principal component analyses of large scale SNP data, and the application of these loadings to other datasets. The use of externally supplied allele frequencies for standardizing the input snp.matrix is required when applying loadings calculated from one dataset to a different dataset
The resulting matrix product
David Clayton [email protected]
##-- ##-- Calculate first two principal components and their loading, and verify ##-- # Make a snp.matrix with a small number of rows data(testdata) small <- Autosomes[1:20,] # Calculate the X.X-transpose matrix xx <- xxt(small, correct.for.missing=FALSE) # Calculate the first two principal components and corresponding eigenvalues eigvv <- eigen(xx, symmetric=TRUE) pc <- eigvv$vectors[,1:2] ev <- eigvv$values[1:2] # Calculate loadings for first two principal components Dinv <- diag(1/sqrt(ev)) loadings <- snp.pre(small, Dinv %*% t(pc)) # Now apply loadings back to recalculate the principal components pc.again <- snp.post(small, t(loadings) %*% Dinv) print(cbind(pc, pc.again))##-- ##-- Calculate first two principal components and their loading, and verify ##-- # Make a snp.matrix with a small number of rows data(testdata) small <- Autosomes[1:20,] # Calculate the X.X-transpose matrix xx <- xxt(small, correct.for.missing=FALSE) # Calculate the first two principal components and corresponding eigenvalues eigvv <- eigen(xx, symmetric=TRUE) pc <- eigvv$vectors[,1:2] ev <- eigvv$values[1:2] # Calculate loadings for first two principal components Dinv <- diag(1/sqrt(ev)) loadings <- snp.pre(small, Dinv %*% t(pc)) # Now apply loadings back to recalculate the principal components pc.again <- snp.post(small, t(loadings) %*% Dinv) print(cbind(pc, pc.again))
This function fits a generalized linear model with phenotype as dependent variable and, optionally, one or more potential confounders of a phenotype-genotype association as independent variable. A series of SNPs (or small groups of SNPs) are then tested for additional association with phenotype. In order to protect against misspecification of the variance function, "robust" tests may be selected.
snp.rhs.tests(formula, family = "binomial", link, weights, subset, data = parent.frame(), snp.data, tests=NULL, robust = FALSE, control = glm.test.control(maxit=20, epsilon=1e-4, R2Max=0.98), allow.missing = 0.01)snp.rhs.tests(formula, family = "binomial", link, weights, subset, data = parent.frame(), snp.data, tests=NULL, robust = FALSE, control = glm.test.control(maxit=20, epsilon=1e-4, R2Max=0.98), allow.missing = 0.01)
formula |
The base model formula, with phenotype as dependent variable |
family |
A string defining the generalized linear model
family. This currently should (partially) match one of
|
link |
A string defining the link function for the GLM. This
currently should (partially) match one of |
data |
The dataframe in which the base model is to be fitted |
snp.data |
An object of class |
tests |
Either a vector of column names or numbers for the SNPs
to be tested, or a list of short vectors defining groups of SNPs to be
tested (again by name or number). The default action is to carry out
all single SNP tests, but
|
weights |
"Prior" weights in the generalized linear model |
subset |
Array defining the subset of rows of |
robust |
If |
control |
An object giving parameters for the IRLS algorithm fitting of the base model and for the acceptable aliasing amongst new terms to be tested. See\ codeglm.test.control |
allow.missing |
The maximum proportion of SNP genotype that can be missing before it becomes necessary to refit the base model |
The tests used are asymptotic chi-squared tests based on the vector of first and second derivatives of the log-likelihood with respect to the parameters of the additional model. The "robust" form is a generalized score test in the sense discussed by Boos(1992). The "base" model is first fitted, and a score test is performed for addition of one or more SNP genotypes to the model. Homozygous SNP genotypes are coded 0 or 2 and heterozygous genotypes are coded 1. For SNPs on the X chromosome, males are coded as homozygous females. For X SNPs, it will often be appropriate to include sex of subject in the base model (this is not done automatically).
If a data argument is supplied, the snp.data and
data objects are aligned by rowname. Otherwise all variables in
the model formulae are assumed to be stored in the same order as the
columns of the snp.data object.
A data frame containing, for each SNP,
Chi.squared |
The value of the chi-squared test statistic |
Df |
The corresponding degrees of freedom |
Df.residual |
The residual degrees of freedom for the base model; i.e. the number of observations minus the number of parameters fitted |
For the binomial family model, the base model can, in some circumstances, lead to perfect prediction of some observations (i.e. fitted probabilities of 0 or 1). These observations are ignored in subsequent calculations; in particular they are not counted in the residual degrees of freedom. Similarly for Poisson means fitted exactly to zero.
A factor (or
several factors) may be included as arguments to the function
strata(...) in the formula. This fits all
interactions of the factors so included, but leads to faster
computation than fitting these in the normal way. Additionally, a
cluster(...) call may be included in the base model
formula. This identifies clusters of potentially correlated
observations (e.g. for members of the same family); in this case, an
appropriate robust estimate of the variance of the score test is used.
David Clayton [email protected]
Boos, Dennis D. (1992) On generalized score tests. The American Statistician, 46:327-333.
single.snp.tests, snp.lhs.tests,
snp.matrix-class, X.snp.matrix-class
data(testdata) library(survival) # strata slt3 <- snp.rhs.tests(cc~strata(region), family="binomial", data=subject.data, snp.data = Autosomes, tests=1:10) print(slt3)data(testdata) library(survival) # strata slt3 <- snp.rhs.tests(cc~strata(region), family="binomial", data=subject.data, snp.data = Autosomes, tests=1:10) print(slt3)
All the dirty details that doesn't belong elsewhere. At the
moment just for hiding references to the genotype-class and
haplotype-class class which is in the genetics package.
This dataset comprises several data frames from a fictional (and unrealistically small) study. The dataset started off as real data from a screen of non-synonymous SNPs for association with type 1 diabetes, but the original identifiers have been removed and a random case/control status has been generated.
data(testdata)data(testdata)
There are five data objects in the dataset:
AutosomesAn object of class "snp.matrix" containing
genotype calls for 400 subjects at 9445 autosomal SNPs
XchromosomeAn object of class "X.snp.matrix"
containing
genotype calls for 400 subjects at 155 SNPs on the X chromosome
AsnpsA dataframe containing information about the autosomal
SNPs. Here it contains only one variable, chromosome,
indicating the chromosomes on which the SNPs are
located
XsnpsA dataframe containing information about the X
chromosome
SNPs. Here it is empty and is only included for completeness
subject.dataA dataframe containing information about the
subjects from whom each row of SNP data was obtained. Here it
contains:
ccCase-control status
sexSex
regionGeographical region of residence
The data were obtained from the diabetes and inflammation laboratory (see http://www-gene.cimr.cam.ac.uk/todd)
http://www-gene.cimr.cam.ac.uk/clayton
data(testdata) Autosomes Xchromosome summary(Asnps) summary(Xsnps) summary(subject.data) summary(summary(Autosomes)) summary(summary(Xchromosome))data(testdata) Autosomes Xchromosome summary(Asnps) summary(Xsnps) summary(subject.data) summary(summary(Autosomes)) summary(summary(Xchromosome))
This function is closely modelled on write.table. It writes an
object of class snp.matrix as a text file with one line for
each row of the matrix. Genotpyes are written in numerical form,
i.e. as 0, 1 or 2 (where 1 denotes heterozygous).
write.snp.matrix(x, file, append = FALSE, quote = TRUE, sep = " ", eol = "\n", na = "NA", row.names = TRUE, col.names = TRUE)write.snp.matrix(x, file, append = FALSE, quote = TRUE, sep = " ", eol = "\n", na = "NA", row.names = TRUE, col.names = TRUE)
x |
The object to be written |
file |
The name of the output file |
append |
If |
quote |
If |
sep |
The string separating entries within a line |
eol |
The string terminating each line |
na |
The string written for missing genotypes |
row.names |
If |
col.names |
If |
A numeric vector giving the dimensions of the matrix written
David Clayton [email protected]
write.table, snp.matrix-class,
X.snp.matrix-class
This is a convenience function for constructing the sample list from the header of a WTCCC signal file.
wtccc.sample.list(infile)wtccc.sample.list(infile)
infile |
One of the signal files in a set of 23 (it is advisable to use the smaller ones such as number 22, although it shouldn't matter). |
The header of a WTCCC signal file is like this:
AFFYID RSID pos AlleleA AlleleB 12999A2_A 12999A2_B ...
The first 5 fields are discarded. There after, every other token is retained, with the "\_A" or "\_B" part removed to give the sample list.
See also read.wtccc.signals for more details.
The value returned is a character vector contain the sample names or the plate-well names as appropriate.
Hin-Tak Leung [email protected]
Compact representation of data concerning single nucleotide polymorphisms (SNPs) on the X chromosome
Objects can be created by calls of the form new("snp", ...,
Female=...) or
by subset selection from an object of class "X.snp.matrix".
Holds one row or column of an object of class "X.snp.matrix"
.Data:The genotype data coded as 0, 1, 2, or 3. For males are coded as homozygious females
Female:A logical array giving the sex of the sample(s)
Class "snp", directly.
Class "raw", by class "snp".
Class "vector", by class "snp".
signature(from = "X.snp", to = "character"):
map to codes "A/A", "A/B", "B/B", "A/Y", "B/Y", or ""
signature(from = "X.snp", to = "numeric"):
map to codes 0, 1, 2, or NA
signature(from = "X.snp", to = "genotype"): Yet
to be implemented
signature(object = "X.snp"): shows character
representation of the object
David Clayton [email protected]
http://www-gene.cimr.cam.ac.uk/clayton
X.snp.matrix-class,
snp.matrix-class, snp-class
data(testdata) s <- Xchromosome[,1] class(s) sdata(testdata) s <- Xchromosome[,1] class(s) s
This class extends the snp.matrix-class to
deal with SNPs on the X chromosome.
Objects can be created by calls of the form new("X.snp.matrix", x,
Female).
Such objects have an additional slot to objects of class
"snp.matrix"
consisting of a logical array of the same length as the number of
rows. This array indicates whether the sample corresponding to that row
came from a female (TRUE) or a male (FALSE).
.Data:Object of class "matrix" and storage mode
"raw"
Female:Object of class "logical" indicating
sex of samples
Class "snp.matrix", directly, with explicit coerce.
Class "matrix", by class "snp.matrix".
Class "structure", by class "snp.matrix".
Class "array", by class "snp.matrix".
Class "vector", by class "snp.matrix", with explicit coerce.
Class "vector", by class "snp.matrix", with explicit coerce.
signature(x = "X.snp.matrix"): subset
operations. Currently rather slow owing to excessive copying
signature(x = "X.snp.matrix"): subset
assignment operation to replace part of an object
signature(from = "X.snp.matrix", to =
"character"): map to codes 0, 1, 2, or NA
signature(from = "snp.matrix", to =
"X.snp.matrix"):
maps a snp.matrix to an X.snp.matrix. Sex is inferred from the
genotype data since males should not be heterozygous at any locus.
After inferring sex, heterozygous calls for males are set to
NA
signature(object = "X.snp.matrix"): map to codes
"A/A", "A/B", "B/B", "A/Y", "B/Y" or ""
signature(object = "X.snp.matrix"): calculate
call rates, allele frequencies, genotype frequencies,
and chi-square tests for
Hardy-Weinberg equilibrium. Genotype frequencies are calculated for
males and females separately and Hardy-Weinberg equilibrium tests
use only the female data. Allele frequencies are calculated using
data from both males and females. Results are returned as a
dataframe with
column names Calls, Call.rate, MAF, P.AA,
P.AB, P.BB, P.AY, P.BY, and
z.HWE
David Clayton [email protected]
http://www-gene.cimr.cam.ac.uk/clayton
X.snp-class, snp.matrix-class,
snp-class
data(testdata) summary(summary(Xchromosome))data(testdata) summary(summary(Xchromosome))
The input snp.matrix is first normalised by subtracting the mean from each call and dividing by the expected standard deviation under Hardy-Weinberg equilibrium. It is then post-multiplied by its transpose. This is a preliminary step in the computation of principal components.
xxt(snps, correct.for.missing = FALSE, lower.only = FALSE)xxt(snps, correct.for.missing = FALSE, lower.only = FALSE)
snps |
The input matrix, of type |
correct.for.missing |
If |
lower.only |
If |
This computation forms the first step of the calculation of principal
components for genome-wide SNP data. As pointed out by Price et al.
(2006), when the data matrix has more rows than columns it is
most efficient to calculate the eigenvectors of
X.X-transpose, where X is a
snp.matrix whose columns have been normalised to zero mean and
unit variance. For autosomes, the genotypes are given codes 0, 1 or 2
after subtraction of the mean, 2p, are divided by the standard
deviation
sqrt(2p(1-p)) (p is the estimated allele
frequency). For SNPs on the X chromosome in male subjects,
genotypes are coded 0 or 2. Then
the mean is still 2p, but the standard deviation is
2sqrt(p(1-p)).
Missing observations present some difficulty. Price et al. (2006)
recommended replacing missing observations by their means, this being
equivalent to replacement by zeros in the normalised matrix. However
this results in a biased estimate of the complete data
result. Optionally this bias can be corrected by inverse probability
weighting. We assume that the probability that any one call is missing
is small, and can be predicted by a multiplicative model with row
(subject) and column (locus) effects. The estimated probability of a
missing value in a given row and column is then given by
, where R is the row total number of
no-calls, C is the column total of no-calls, and T is the
overall total number of no-calls. Non-missing contributions to
X.X-transpose are then weighted by for
contributions to the diagonal elements, and products of the relevant
pairs of weights for contributions to off–diagonal elements.
A square matrix containing either the complete X.X-transpose matrix, or just its lower triangle
The correction for missing observations can result in an output matrix which is not positive semi-definite. This should not matter in the application for which it is intended
In genome-wide studies, the SNP data will usually be held as a series of
objects (of
class "snp.matrix" or"X.snp.matrix"), one per chromosome.
Note that the X.X-transpose matrices
produced by applying the xxt function to each object in turn
can be added to yield the genome-wide result.
David Clayton [email protected]
Price et al. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nature Genetics, 38:904-9
# make a snp.matrix with a small number of rows data(testdata) small <- Autosomes[1:100,] # Calculate the X.X-transpose matrix xx <- xxt(small, correct.for.missing=TRUE) # Calculate the principal components pc <- eigen(xx, symmetric=TRUE)$vectors# make a snp.matrix with a small number of rows data(testdata) small <- Autosomes[1:100,] # Calculate the X.X-transpose matrix xx <- xxt(small, correct.for.missing=TRUE) # Calculate the principal components pc <- eigen(xx, symmetric=TRUE)$vectors