denovolyzeMultiHits {denovolyzeR}

Determine significance of genes with multiple de novos

Description

Are there more genes containing >1 de novos than expected?

Usage

denovolyzeMultiHits(genes, classes, nsamples, nperms = 100,
  includeGenes = "all", includeClasses = c("syn", "mis", "lof", "prot",
  "all"), nVars = "actual", geneId = "geneName", probTable = NULL,
  misD = NULL, signifP = 3, roundExpected = 1)

Arguments

genes

A vector of genes containing de novo variants.

classes

A vector of classes of de novo variants. Standard supported classes are "syn" (synonymous), "mis" (missense), "non" (nonsense), "splice" (splice), "frameshift" (frameshift) and "lof" (loss of function = non + splice + frameshift). Additional classes that are supported by the code, but are not included in the built-in probability tables, are "stoploss","startloss", "misD" (damaging missense). These labels may be used for user-supplied probability tables. If "misD" is present, then "mis" (in the input) implies non-damaging missense.

nsamples

Number of individuals considered in de novo analysis.

nperms

Number of permutations

includeGenes

Genes to include in analysis. "all" or a vector of gene names.

includeClasses

Determines which variant classes are tabulated in output. In addition to the input classes, summaries can be produced for "prot" (protein-altering = mis + lof), "all", and "protD" (protein damaging = misD + lof, only available if misD included in user-specified probability table). If "misD" is present, then "mis" will return statistics for all missense. Non-damaging missense are not analysed separately.

nVars

Select whether expected number of multihits is determined by "expected" total number of variants , or "actual" total. Actual (default) is more conservative.

geneId

Gene identifier used. One of "hgncID", "hgncSymbol", "enstID", "ensgID" or "geneName" (default, equals ensembl "external_gene_name")

probTable

Probability table. A user-defined table of probabilities can be provided here, to replace the probability table included in the package.

misD

If the user-specified probability table contains probabilities for a sub-category of missense variants (e.g. predicted to be damaging by an in silico algorithm), this column should be called misD, or the alternative name should be specified here.

signifP

Number of significant figures used to round p-values in output.

roundExpected

Number of decimal places used to round expected burdens in output.

Details

See vignette (denovostats_intro) for more information.

Value

Returns a data.frame

Examples

denovolyzeMultiHits(genes=autismDeNovos$gene,
                    classes=autismDeNovos$class,
                    nsamples=1078)