Package 'MouseFM'

Title: In-silico methods for genetic finemapping in inbred mice
Description: This package provides methods for genetic finemapping in inbred mice by taking advantage of their very high homozygosity rate (>95%).
Authors: Matthias Munz [aut, cre] , Inken Wohlers [aut] , Hauke Busch [aut]
Maintainer: Matthias Munz <[email protected]>
License: GPL-3
Version: 1.17.0
Built: 2024-10-30 08:24:45 UTC
Source: https://github.com/bioc/MouseFM

Help Index


Annotate with consequences

Description

Request variant consequences from Variant Effect Predictor (VEP) via Ensembl Rest Service. Not recommended for large queries.

Usage

annotate_consequences(geno, species)

Arguments

geno

Data frame or GenomicRanges::GRanges object including columns rsid, ref, alt.

species

Species name, e.g. mouse (GRCm38) or human (GRCh38).

Value

Data frame.

Examples

geno = finemap("chr1",
  start = 5000000, end = 6000000,
  strain1 = c("C57BL_6J"), strain2 = c("AKR_J", "A_J", "BALB_cJ")
)

df = annotate_consequences(geno[seq_len(10), ], "mouse")

geno.granges = finemap("chr1",
    start = 5000000, end = 6000000,
    strain1 = c("C57BL_6J"), strain2 = c("AKR_J", "A_J", "BALB_cJ"),
    return_obj = "granges"
)

df2 = annotate_consequences(geno.granges[seq_len(10), ], "mouse")

Annotate with genes

Description

Request mouse genes from Ensembl Biomart.

Usage

annotate_mouse_genes(geno, flanking = NULL)

Arguments

geno

Data frame or GenomicRanges::GRanges object including columns chr, pos.

flanking

Size of flanking sequence to be included.

Value

Data frame.

Examples

geno = finemap("chr1",
  start = 5000000, end = 6000000,
  strain1 = c("C57BL_6J"), strain2 = c("AKR_J", "A_J", "BALB_cJ")
)

genes = annotate_mouse_genes(geno, 50000)

Available chromosomes

Description

Available mouse chromosomes.

Usage

avail_chromosomes()

Value

Data frame

Examples

avail_chromosomes()

Available consequences

Description

Available consequence and impact types.

Usage

avail_consequences()

Value

Data frame.

Examples

avail_consequences()$consequence

unique(avail_consequences()$impact)

Available strains

Description

There are 37 strains available.

Usage

avail_strains()

Value

Data frame.

Examples

avail_strains()

Data frame to GenomicRanges::GRanges object

Description

Wrapper for GenomicRanges::makeGRangesFromDataFrame().

Usage

df2GRanges(
  geno,
  chr_name = "chr",
  start_name = "pos",
  end_name = "pos",
  strand_name = NULL,
  ref_version = ref_genome(),
  seq_lengths = NULL,
  is_circular = FALSE
)

Arguments

geno

Data frame.

chr_name

Name of chromosome column. Default is 'chr'.

start_name

Name of start position column. Default is 'pos.'

end_name

Name of end position column. Default is 'pos'

strand_name

Name of end position column. Default is NULL.

ref_version

Reference genome version. Default is 'ref_genome()'.

seq_lengths

List of sequence lengths with sequence name as key. Default is NULL.

is_circular

Whether genome is circular. Default is FALSE.

Value

GenomicRanges::GRanges object.

Examples

geno = finemap("chr1",
  start = 5000000, end = 6000000,
  strain1 = c("C57BL_6J"), strain2 = c("AKR_J", "A_J", "BALB_cJ")
)

geno$strand = "+"
seq_lengths = stats::setNames(
    as.list(avail_chromosomes()$length),
    avail_chromosomes()$chr
)
geno.granges = df2GRanges(geno,
    strand_name = "strand",
    seq_lengths = seq_lengths
)

Fetch

Description

Fetch homozygous genotypes for a specified chromosomal region in 37 inbred mouse strains.

Usage

fetch(
  chr,
  start = NULL,
  end = NULL,
  consequence = NULL,
  impact = NULL,
  return_obj = "dataframe"
)

Arguments

chr

Vector of chromosome names.

start

Optional vector of chromosomal start positions of target regions (GRCm38).

end

Optional vector of chromosomal end positions of target regions (GRCm38).

consequence

Optional vector of consequence types.

impact

Optional vector of impact types.

return_obj

The user can choose to get the result to be returned as data frame ("dataframe") or as a GenomicRanges::GRanges ("granges") object. Default value is "dataframe".

Value

Data frame or GenomicRanges::GRanges object containing result data.

Examples

geno = fetch("chr7", start = 5000000, end = 6000000)

comment(geno)

Finemapping of genetic regions

Description

Finemapping of genetic regions in 37 inbred mice by taking advantage of their very high homozygosity rate (>95 chromosomal regions (GRCm38), this method extracts homozygous SNVs for which the allele differs between two sets of strains (e.g. case vs controls) and outputs respective causal SNV/gene candidates.

Usage

finemap(
  chr,
  start = NULL,
  end = NULL,
  strain1,
  strain2,
  consequence = NULL,
  impact = NULL,
  thr1 = 0,
  thr2 = 0,
  return_obj = "dataframe"
)

Arguments

chr

Vector of chromosome names.

start

Optional vector of chromosomal start positions of target regions (GRCm38).

end

Optional vector of chromosomal end positions of target regions (GRCm38).

strain1

First strain set with strains from avail_strains().

strain2

Second strain set with strains from avail_strains().

consequence

Optional vector of consequence types.

impact

Optional vector of impact types.

thr1

Number discordant strains in strain1. Between 0 and length(strain1)-1. 0 by default.

thr2

Number discordant strains in strain2. Between 0 and length(strain2)-1. 0 by default.

return_obj

The user can choose to get the result to be returned as data frame ("dataframe") or as a GenomicRanges::GRanges ("granges") object. Default value is "dataframe".

Value

Data frame or GenomicRanges::GRanges object containing result data.

Examples

geno = finemap("chr1",
    start = 5000000, end = 6000000,
    strain1 = c("C57BL_6J"), strain2 = c(
        "129S1_SvImJ", "129S5SvEvBrd",
        "AKR_J"
    )
)

comment(geno)

Best strain combinations

Description

Get best strain combinations

Usage

get_top(red, n_top)

Arguments

red

Reduction factors data frame.

n_top

Number of combinations to be returned.

Value

Data frame

Examples

l = prio("chr1",
  start = 5000000, end = 6000000,
  strain1 = "C57BL_6J", strain2 = "AKR_J"
)

get_top(l$reduction, 3)

Get backend service url

Description

Get backend service URL. Default: http://45.85.146.64:9000/rest/finemap/

Usage

getURL()

Value

URL string.

Examples

getURL()

GenomicRanges::GRanges object to data frame

Description

Wrapper for as.data.frame().

Usage

GRanges2df(granges)

Arguments

granges

GenomicRanges::GRanges object

Value

Data frame.

Examples

geno.granges = finemap("chr1",
    start = 5000000, end = 6000000,
    strain1 = c("C57BL_6J"), strain2 = c("AKR_J", "A_J", "BALB_cJ"),
    return_obj = "granges"
)

geno = GRanges2df(geno.granges)

Prioritization of inbred mouse strains for refining genetic regions

Description

This method allows to select strain combinations which best refine a specified genetic region (GRCm38). E.g. if a crossing experiment with two inbred mouse strains 'strain1' and 'strain2' resulted in a QTL, the outputted strain combinations can be used to refine the respective region in further crossing experiments.

Usage

prio(
  chr,
  start = NULL,
  end = NULL,
  strain1 = NULL,
  strain2 = NULL,
  consequence = NULL,
  impact = NULL,
  min_strain_benef = 0.1,
  max_set_size = 3,
  return_obj = "dataframe"
)

Arguments

chr

Vector of chromosome names.

start

Optional vector of chromosomal start positions of target regions (GRCm38).

end

Optional vector of chromosomal end positions of target regions (GRCm38).

strain1

First strain set with strains from avail_strains().

strain2

Second strain set with strains from avail_strains().

consequence

Optional vector of consequence types.

impact

Optional vector of impact types.

min_strain_benef

Minimum reduction factor (min) of a single strain.

max_set_size

Maximum set of strains.

return_obj

The user can choose to get the result to be returned as data frame ("dataframe") or as a GenomicRanges::GRanges ("granges") object. Default value is "data frame".

Value

Data frame

Examples

res = prio("chr1",
  start = 5000000, end = 6000000, strain1 = "C57BL_6J",
  strain2 = "AKR_J"
)

comment(res$genotypes)

Reference genome version

Description

Returns version of reference genome used in package MouseFM.

Usage

ref_genome()

Value

Vector.

Examples

ref_genome()

Set backend service url

Description

Set backend service URL. Default: http://45.85.146.64:9000/rest/finemap/

Usage

setURL(url)

Arguments

url

URL of backend service. With backslash at the end.

Value

No return value.

Examples

setURL("http://45.85.146.64:9000/rest/finemap/")

Visualize

Description

Visualize reduction factors

Usage

vis_reduction_factors(geno, red, n_top)

Arguments

geno

Genotype data frame or GenomicRanges::GRanges object.

red

Reduction factor data frame.

n_top

Number if combinations to be returned.

Value

Data frame

Examples

l = prio(c("chr1", "chr2"),
  start = c(5000000, 5000000),
  end = c(6000000, 6000000), strain1 = c("C3H_HeH"), strain2 = "AKR_J"
)

plots = vis_reduction_factors(l$genotypes, l$reduction, 2)

plots[[1]]
plots[[2]]