runMiDAS: Run MiDAS statistical analysis

In Genentech/midasHLA: R package for immunogenomics data handling and association analysis

Run MiDAS statistical analysis

Description

runMiDAS perform association analysis on MiDAS data using statistical model of choice. Function is intended for use with prepareMiDAS. See examples section.

Usage

runMiDAS(
  object,
  experiment,
  inheritance_model = NULL,
  conditional = FALSE,
  omnibus = FALSE,
  omnibus_groups_filter = NULL,
  lower_frequency_cutoff = NULL,
  upper_frequency_cutoff = NULL,
  correction = "bonferroni",
  n_correction = NULL,
  exponentiate = FALSE,
  th = 0.05,
  th_adj = TRUE,
  keep = FALSE,
  rss_th = 1e-07
)

Arguments

object	An existing fit from a model function such as lm, glm and many others.
experiment	String indicating the experiment associated with object's MiDAS data to use. Valid values includes: "hla_alleles", "hla_aa", "hla_g_groups", "hla_supertypes", "hla_NK_ligands", "kir_genes", "kir_haplotypes", "hla_kir_interactions", "hla_divergence", "hla_het", "hla_custom", "kir_custom". See prepareMiDAS for more information.
inheritance_model	String specifying inheritance model to use. Available choices are "dominant", "recessive", "additive".
conditional	Logical flag indicating if conditional analysis should be performed.
omnibus	Logical flag indicating if omnibus test should be used.
omnibus_groups_filter	Character vector specifying omnibus groups to use.
lower_frequency_cutoff	Number giving lower frequency threshold. Numbers greater than 1 are interpreted as the number of feature occurrences, numbers between 0 and 1 as fractions.
upper_frequency_cutoff	Number giving upper frequency threshold. Numbers greater than 1 are interpreted as the number of feature occurrences, numbers between 0 and 1 as fractions.
correction	String specifying multiple testing correction method. See details for further information.
n_correction	Integer specifying number of comparisons to consider during multiple testing correction calculations. For Bonferroni correction it is possible to specify a number lower than the number of comparisons being made. This is useful in cases when knowledge about the biology or redundance of alleles reduces the need for correction. For other methods it must be at least equal to the number of comparisons being made; only set this (to non-default) when you know what you are doing!
exponentiate	Logical flag indicating whether or not to exponentiate the coefficient estimates. Internally this is passed to tidy. This is typical for logistic and multinomial regressions, but a bad idea if there is no log or logit link. Defaults to FALSE.
th	Number specifying threshold for a variable to be considered significant.
th_adj	Logical flag indicating if adjusted p-value should be used as threshold criteria, otherwise unadjusted p-value is used.
keep	Logical flag indicating if the output should be a list of results resulting from each selection step. Default is to return only the final result.
rss_th	Number specifying residual sum of squares threshold at which function should stop adding additional variables. As the residual sum of squares approaches 0 the perfect fit is obtained making further attempts at variable selection nonsense. This behavior can be controlled using rss_th.

Details

By default statistical analysis is performed iteratively on each variable in selected experiment. This is done by substituting placeholder in the object's formula with each variable in the experiment.

Setting conditional argument to TRUE will cause the statistical analysis to be performed in a stepwise conditional testing manner, adding the previous top-associated variable as a covariate to object's formula. The analysis stops when there is no more significant variables, based on self-defined threshold (th argument). Either adjusted or unadjusted p-values can be used as the selection criteria, which is controlled using th_adj argument.

Setting omnibus argument to TRUE will cause the statistical analysis to be performed iteratively on groups of variables (like residues at particular amino acid position) using likelihood ratio test.

Argument inheritance_model specifies the inheritance model that should be applyed to experiment's data. Following choices are available:

• "dominant" carrier status is sufficient for expression of the phenotype (non-carrier: 0, heterozygous & homozygous carrier: 1).

• "recessive" two copies are required for expression of the phenotype (non-carrier & heterozygous carrier: 0, homozygous carrier: 1).

• "additive" allele dosage matters, homozygous carriers show stronger phenotype expression or higher risk than heterozygous carriers (non-carrier = 0, heterozygous carrier = 1, homozygous carrier = 2).

• "overdominant" heterozygous carriers are at higher risk compared to non-carriers or homozygous carriers (non-carrier & homozygous carrier = 0, heterozygous carrier = 1).

correction specifies p-value adjustment method to use, common choice is Benjamini & Hochberg (1995) ("BH"). Internally this is passed to p.adjust.

Value

Analysis results, depending on the parameters:

conditional=FALSE, omnibus=FALSE

Tibble with first column "term" holding names of tested variables (eg. alleles). Further columns depends on the used model and are determined by associated tidy function. Generally they will include "estimate", "std.error", "statistic", "p.value", "conf.low", "conf.high", "p.adjusted".

conditional=TRUE, omnibus=FALSE

Tibble or a list of tibbles, see keep argument. The first column "term" hold names of tested variables. Further columns depends on the used model and are determined by associated tidy function. Generally they will include "estimate", "std.error", "statistic", "p.value", "conf.low", "conf.high", "p.adjusted".

conditional=FALSE, omnibus=TRUE

Tibble with first column holding names of tested omnibus groups (eg. amino acid positions) and second names of variables in the group (eg. residues). Further columns are: "df" giving difference in degrees of freedom between base and extended model, "statistic" giving Chisq statistic, "p.value" and "p.adjusted".

conditional=TRUE, omnibus=TRUE

Tibble or a list of tibbles, see keep argument. The first column hold names of tested omnibus groups (eg. amino acid positions), second column hold names of variables in the group (eg. residues). Further columns are: "df" giving difference in degrees of freedom between base and extended model, "statistic" giving Chisq statistic, "p.value" and "p.adjusted".

Examples

# create MiDAS object
midas <- prepareMiDAS(hla_calls = MiDAS_tut_HLA,
                      colData = MiDAS_tut_pheno,
                      experiment = c("hla_alleles", "hla_aa")
)

# construct statistical model
object <- lm(disease ~ term, data = midas)

# run analysis
runMiDAS(object, experiment = "hla_alleles", inheritance_model = "dominant")

# omnibus test
# omnibus_groups_filter argument can be used to restrict omnibus test only
# to selected variables groups, here we restrict the analysis to HLA-A
# positions 29 and 43.
runMiDAS(
  object,
  experiment = "hla_aa",
  inheritance_model = "dominant",
  omnibus = TRUE,
  omnibus_groups_filter = c("A_29", "A_43")
)

Genentech/midasHLA documentation built on Feb. 12, 2024, 9:38 a.m.