concur: Copy Number Profile Curve-Based Association Test

Description Usage Arguments Details Value References Examples

View source: R/concur.R

Description

Implements a kernel-based association test for CNV aggregate analysis in a certain genomic region (e.g., gene set, chromosome, or genome) that is robust to the within-locus and across-locus etiologoical heterogeneity, and bypass the need to define a "locus" unit for CNVs.

Usage

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concur(
  cnv,
  X,
  pheno,
  phenoY,
  phenoType,
  ...,
  nCore = 1L,
  outFileKernel = NULL,
  verbose = TRUE
)

Arguments

cnv

A character or data.frame object. If character, the name of the data file containing the CNV data (with a header). If data.frame, the CNV data. The data must contain the following columns: "ID", "CHR", "BP1", "BP2", "TYPE", where "ID" is a unique patient id, "CHR" is the CNV chromosome, "BP1" is the start location in base pairs or kilo-base pairs, "BP2" is the end location in base pairs or kilo-base pairs, and "TYPE" is the CNV copy number.

X

A character or data.frame object. If character, the name of the data file containing the covariate data (with a header). If data.frame, the covariate data. The data must contain a column titled "ID" containing a unique patient id. This column must contain the patient identifiers of the CNV data specified in input cnv; however, it can contain patient identifiers not contained in cnv. Further, inputs X and pheno must contain the same patient identifiers. Categorical variables must be translated into design matrix format.

pheno

A character or data.frame object. If character, the name of the data file containing the phenotype data (with a header). If data.frame, the phenotype data. The data must contain a column titled "ID" containing a unique patient id. This column must contain the patient identifiers of the CNV data specified in input cnv; however, it can contain patient identifiers not contained in cnv. Further, inputs X and pheno must contain the same patient identifiers.

phenoY

A character object. The column name in input pheno containing the phenotype of interest.

phenoType

A character object. Must be one of of {"bin", "cont"} indicating if input phenoY (i.e., the phenotype of interest) is binary or continuous.

...

Ignored. Included to require named inputs.

nCore

An integer object. If nCore > 1, package parallel is used to calculate the kernel. Though the methods of package CompQuadForm dominate the time profile, setting nCore > 1L can improve computation times.

outFileKernel

A character object or NULL. If a character, the file in which the kernel is to be saved. If NULL, the kernel is returned by the function.

verbose

A logical object. If TRUE, progress information is printed to the screen.

Details

The CNV data must adhere to the following conditions:

Violations of these conditions typically occur when data are rounded to a desired resolution. For example

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 ID CHR      BP1      BP2 TYPE
  1  13 10112087 10112414    3

becomes upon rounding to kilo

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 ID CHR   BP1   BP2 TYPE
  1  13 10112 10112    3     .

These cases should either be discarded or modified to be of length 1, e.g.,

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 ID CHR   BP1   BP2 TYPE
  1  13 10112 10113    3     .

As an example of condition 2

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 ID CHR    BP1   BP2 TYPE
  1  13 100768 101100    3
  1  13 101100 101299    1

should be modified to one of

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 ID CHR    BP1   BP2 TYPE
  1  13 100768 101100    3
  1  13 101101 101299    1

or

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 ID CHR    BP1   BP2 TYPE
  1  13 100768 101099    3
  1  13 101100 101299    1     .

Additionally,

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 ID CHR    BP1   BP2 TYPE
  1  13 100768 101100    3
  1  13 101100 101299    3

should be combined as

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 ID CHR    BP1   BP2 TYPE
  1  13 100768 101299    3     .

Value

A list containing the kernel (or its file name) and the p-value.

References

Brucker, A., Lu, W., Marceau West, R., Yu, Q-Y., Hsiao, C. K., Hsiao, T-H., Lin, C-H., Magnusson, P. K. E., Holloway, S. T., Sullivan, P. F., Szatkiewicz, J. P., Lu, T-P., and Tzeng, J-Y. Association testing using Copy Number Profile Curves (CONCUR) enhances power in copy number variant analysis. <doi:10.1101/666875>.

Examples

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data(cnvData)

# limit data for examples
exCNV <- cnvData$ID %in% paste0("P", 1:150)
exCOV <- covData$ID %in% paste0("P", 1:150)
exPHE <- phenoData$ID %in% paste0("P", 1:150)

# binary phenoType
results <- concur(cnv = cnvData[exCNV,],
                  X = covData[exCOV,],
                  pheno = phenoData[exPHE,],
                  phenoY = 'PHEB',
                  phenoType = 'bin',
                  nCore = 1L,
                  outFileKernel = NULL,
                  verbose = TRUE)

# continuous phenoType
results <- concur(cnv = cnvData[exCNV,],
                  X = covData[exCOV,],
                  pheno = phenoData[exPHE,],
                  phenoY = 'PHEC',
                  phenoType = 'cont',
                  nCore = 1L,
                  outFileKernel = NULL,
                  verbose = TRUE)

CONCUR documentation built on Aug. 6, 2020, 5:10 p.m.

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