coordinate-mapping-methods: Map range coordinates between transcripts and genome space

Description Usage Arguments Details Value Author(s) See Also Examples

Description

Map range coordinates between features in the transcriptome and genome (reference) space.

See ?mapToAlignments in the GenomicAlignments package for mapping coordinates between reads (local) and genome (reference) space using a CIGAR alignment.

Usage

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## mapping to transcripts
## S4 method for signature 'GenomicRanges,GenomicRanges'
mapToTranscripts(x, transcripts,
          ignore.strand = FALSE)
## S4 method for signature 'GenomicRanges,GRangesList'
mapToTranscripts(x, transcripts,
          ignore.strand = FALSE, intronJunctions=FALSE)
## S4 method for signature 'ANY,TxDb'
mapToTranscripts(x, transcripts, ignore.strand = FALSE,
          extractor.fun = GenomicFeatures::transcripts, ...)
## S4 method for signature 'GenomicRanges,GRangesList'
pmapToTranscripts(x, transcripts,
          ignore.strand = FALSE)

## mapping from transcripts
## S4 method for signature 'GenomicRanges,GRangesList'
mapFromTranscripts(x, transcripts,
          ignore.strand = FALSE)
## S4 method for signature 'GenomicRanges,GRangesList'
pmapFromTranscripts(x, transcripts,
          ignore.strand = FALSE)
## S4 method for signature 'IntegerRanges,GRangesList'
pmapFromTranscripts(x, transcripts)

Arguments

x

GenomicRanges object of positions to be mapped. The seqnames of x are used in mapFromTranscripts, i.e., when mapping from transcripts to the genome. In the case of pmapFromTranscripts, x can be an IntegerRanges object.

transcripts

A named GenomicRanges or GRangesList object used to map between x and the result. The ranges can be any feature in the transcriptome extracted from a TxDb (e.g., introns, exons, cds regions). See ?transcripts and ?transcriptsBy for a list of extractor functions.

The transcripts object must have names. When mapping from transcripts to the genome, they are used to determine mapping pairs; in the reverse direction they become the seqlevels of the output object.

ignore.strand

When ignore.strand is TRUE, strand is ignored in overlaps operations (i.e., all strands are considered "+") and the strand in the output is '*'.

When ignore.strand is FALSE strand in the output is taken from the transcripts argument. When transcripts is a GRangesList, all inner list elements of a common list element must have the same strand or an error is thrown.

Mapped position is computed by counting from the transcription start site (TSS) and is not affected by the value of ignore.strand.

intronJunctions

Logical to indicate if intronic ranges in x should be reported.

This argument is only supported in mapToTranscripts when transcripts is a GRangesList. When transcripts is a GRangesList, individual ranges can be thought of as exons and the spaces between the ranges as introns.

When intronJunctions=TRUE, ranges that fall completely "within" an intron are reported as a zero-width range (start and end are taken from the ranges they fall between). A metadata column called "intronic" is returned with the GRanges and marked as TRUE for these ranges. By default, intronJunctions=FALSE and these ranges are not mapped.

Ranges that have either the start or end in an intron are considered "non hits" and are never mapped. Ranges that span introns are always mapped. Neither of these range types are controlled by the intronJunctions argument.

extractor.fun

Function to extract genomic features from a TxDb object.

This argument is only applicable to mapToTranscripts when transcripts is a TxDb object. The extractor should be the name of a function (not a character()) described on the ?transcripts, ?transcriptsBy, or ?microRNAs man page.

Valid extractor functions:

  • transcripts ## default

  • exons

  • cds

  • genes

  • promoters

  • exonicParts

  • intronicParts

  • transcriptsBy

  • exonsBy

  • cdsBy

  • intronsByTranscript

  • fiveUTRsByTranscript

  • threeUTRsByTranscript

  • microRNAs

  • tRNAs

...

Additional arguments passed to extractor.fun functions.

Details

In GenomicFeatures >= 1.21.10, the default for ignore.strand was changed to FALSE for consistency with other methods in the GenomicRanges and GenomicAlignments packages. Additionally, the mapped position is computed from the TSS and does not depend on the ignore.strand argument. See the section on ignore.strand for details.

Value

pmapToTranscripts returns a GRanges the same length as x.

pmapFromTranscripts returns a GRanges when transcripts is a GRanges and a GRangesList when transcripts is a GRangesList. In both cases the return object is the same length as x. The rational for returning the GRangesList is to preserve exon structure; ranges in a list element that are not overlapped by x are returned as a zero-width range. The GRangesList return object will have no seqlevels called "UNMAPPED"; those will only occur when a GRanges is returned.

mapToTranscripts and mapFromTranscripts return GRanges objects that vary in length similar to a Hits object. The result contains mapped records only; strand mismatch and out of bound ranges are not returned. xHits and transcriptsHits metadata columns (similar to the queryHits and subjectHits of a Hits object) indicate elements of x and transcripts used in the mapping.

When intronJunctions is TRUE, mapToTranscripts returns an extra metdata column named intronic to identify the intron ranges.

When mapping to transcript coordinates, seqlevels of the output are the names on the transcripts object and most often these will be transcript names. When mapping to the genome, seqlevels of the output are the seqlevels of transcripts which are usually chromosome names.

Author(s)

V. Obenchain, M. Lawrence and H. Pagès

See Also

Examples

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## ---------------------------------------------------------------------
## A. Basic Use: Conversion between CDS and Exon coordinates and the
##    genome
## ---------------------------------------------------------------------

## Gene "Dgkb" has ENTREZID "217480":
library(org.Mm.eg.db)
Dgkb_geneid <- get("Dgkb", org.Mm.egSYMBOL2EG)

## The gene is on the positive strand, chromosome 12:
library(TxDb.Mmusculus.UCSC.mm10.knownGene)
txdb <- TxDb.Mmusculus.UCSC.mm10.knownGene
tx_by_gene <- transcriptsBy(txdb, by="gene")
Dgkb_transcripts <- tx_by_gene[[Dgkb_geneid]]
Dgkb_transcripts  # all 7 Dgkb transcripts are on chr12, positive strand

## To map coordinates from local CDS or exon space to genome 
## space use mapFromTranscripts().

## When mapping CDS coordinates to genome space the 'transcripts'
## argument is the collection of CDS regions by transcript.
coord <- GRanges("chr12", IRanges(4, width=1))
## Get the names of the transcripts in the gene:
Dgkb_tx_names <- mcols(Dgkb_transcripts)$tx_name
Dgkb_tx_names
## Use these names to isolate the region of interest:
cds_by_tx <- cdsBy(txdb, "tx", use.names=TRUE)
Dgkb_cds_by_tx <- cds_by_tx[intersect(Dgkb_tx_names, names(cds_by_tx))]
## Dgkb CDS grouped by transcript (no-CDS transcripts omitted):
Dgkb_cds_by_tx
lengths(Dgkb_cds_by_tx)  # nb of CDS per transcript
## A requirement for mapping from transcript space to genome space
## is that seqnames in 'x' match the names in 'transcripts'.
names(Dgkb_cds_by_tx) <- rep(seqnames(coord), length(Dgkb_cds_by_tx))
## There are 6 results, one for each transcript.
mapFromTranscripts(coord, Dgkb_cds_by_tx)

## To map exon coordinates to genome space the 'transcripts'
## argument is the collection of exon regions by transcript.
coord <- GRanges("chr12", IRanges(100, width=1))
ex_by_tx <- exonsBy(txdb, "tx", use.names=TRUE)
Dgkb_ex_by_tx <- ex_by_tx[Dgkb_tx_names]
names(Dgkb_ex_by_tx) <- rep(seqnames(coord), length(Dgkb_ex_by_tx))
## Again the output has 6 results, one for each transcript.
mapFromTranscripts(coord, Dgkb_ex_by_tx)

## To go the reverse direction and map from genome space to
## local CDS or exon space, use mapToTranscripts().

## Genomic position 37981944 maps to CDS position 4:
coord <- GRanges("chr12", IRanges(37981944, width=1))
mapToTranscripts(coord, Dgkb_cds_by_tx)

## Genomic position 37880273 maps to exon position 100:
coord <- GRanges("chr12", IRanges(37880273, width=1))
mapToTranscripts(coord, Dgkb_ex_by_tx)


## The following examples use more than 2GB of memory, which is more
## than what 32-bit Windows can handle:
is_32bit_windows <- .Platform$OS.type == "windows" &&
                    .Platform$r_arch == "i386"
if (!is_32bit_windows) {
## ---------------------------------------------------------------------
## B. Map sequence locations in exons to the genome
## ---------------------------------------------------------------------

## NAGNAG alternative splicing plays an essential role in biological
## processes and represents a highly adaptable system for
## posttranslational regulation of gene function. The majority of
## NAGNAG studies largely focus on messenger RNA. A study by Sun,
## Lin, and Yan (http://www.hindawi.com/journals/bmri/2014/736798/)
## demonstrated that NAGNAG splicing is also operative in large
## intergenic noncoding RNA (lincRNA). One finding of interest was
## that linc-POLR3G-10 exhibited two NAGNAG acceptors located in two
## distinct transcripts: TCONS_00010012 and TCONS_00010010.

## Extract the exon coordinates of TCONS_00010012 and TCONS_00010010:
lincrna <- c("TCONS_00010012", "TCONS_00010010")
library(TxDb.Hsapiens.UCSC.hg19.lincRNAsTranscripts)
txdb <- TxDb.Hsapiens.UCSC.hg19.lincRNAsTranscripts
exons <- exonsBy(txdb, by="tx", use.names=TRUE)[lincrna]
exons

## The two NAGNAG acceptors were identified in the upstream region of
## the fourth and fifth exons located in TCONS_00010012.
## Extract the sequences for transcript TCONS_00010012:
library(BSgenome.Hsapiens.UCSC.hg19)
genome <- BSgenome.Hsapiens.UCSC.hg19
exons_seq <- getSeq(genome, exons[[1]])

## TCONS_00010012 has 4 exons:
exons_seq

## The most common triplet among the lincRNA sequences was CAG. Identify
## the location of this pattern in all exons.
cag_loc <- vmatchPattern("CAG", exons_seq)

## Convert the first occurance of CAG in each exon back to genome
## coordinates.
first_loc <- do.call(c, sapply(cag_loc, "[", 1, simplify=TRUE))
pmapFromTranscripts(first_loc, exons[[1]])

## ---------------------------------------------------------------------
## C. Map dbSNP variants to CDS or cDNA coordinates
## ---------------------------------------------------------------------

## The GIPR gene encodes a G-protein coupled receptor for gastric
## inhibitory polypeptide (GIP). Originally GIP was identified to
## inhibited gastric acid secretion and gastrin release but was later
## demonstrated to stimulate insulin release in the presence of elevated
## glucose.

## In this example 5 SNPs located in the GIPR gene are mapped to cDNA
## coordinates. A list of SNPs in GIPR can be downloaded from dbSNP or
## NCBI.
rsids <- c("rs4803846", "rs139322374", "rs7250736", "rs7250754",
           "rs9749185")

## Extract genomic coordinates with a SNPlocs package.
library(SNPlocs.Hsapiens.dbSNP144.GRCh38)
snps <- snpsById(SNPlocs.Hsapiens.dbSNP144.GRCh38, rsids)

## Gene regions of GIPR can be extracted from a TxDb package of
## compatible build. The TxDb package uses Entrez gene identifiers
## and GIPR is a gene symbol. Let's first lookup its Entrez gene ID.
library(org.Hs.eg.db)
GIPR_geneid <- get("GIPR", org.Hs.egSYMBOL2EG)

## The transcriptsBy() extractor returns a range for each transcript that
## includes the UTR and exon regions (i.e., cDNA).
library(TxDb.Hsapiens.UCSC.hg38.knownGene)
txdb <- TxDb.Hsapiens.UCSC.hg38.knownGene
tx_by_gene <- transcriptsBy(txdb, "gene")
GIPR_transcripts <- tx_by_gene[GIPR_geneid]
GIPR_transcripts  # all 8 GIPR transcripts are on chr19, positive strand

## Before mapping, the chromosome names (seqlevels) in the two
## objects must be harmonized. The style is NCBI for 'snps' and
## UCSC for 'GIPR_transcripts'.
seqlevelsStyle(snps)
seqlevelsStyle(GIPR_transcripts)

## Modify the style (and genome) in 'snps' to match 'GIPR_transcripts'.
seqlevelsStyle(snps) <- seqlevelsStyle(GIPR_transcripts)

## The 'GIPR_transcripts' object is a GRangesList of length 1. This single
## list element contains the cDNA range for 8 different transcripts. To
## map to each transcript individually 'GIPR_transcripts' must be unlisted
## before mapping.

## Map all 5 SNPS to all 8 transcripts:
mapToTranscripts(snps, unlist(GIPR_transcripts))

## Map the first SNP to transcript "ENST00000590918.5" and the second to
## "ENST00000263281.7".
pmapToTranscripts(snps[1:2], unlist(GIPR_transcripts)[1:2])

## The cdsBy() extractor returns coding regions by gene or by transcript.
## Extract the coding regions for transcript "ENST00000263281.7".
cds <- cdsBy(txdb, "tx", use.names=TRUE)["ENST00000263281.7"]
cds

## The 'cds' object is a GRangesList of length 1 containing all CDS ranges
## for the single transcript "ENST00000263281.7".

## To map to the concatenated group of ranges leave 'cds' as a GRangesList.
mapToTranscripts(snps, cds)

## Only the second SNP could be mapped. Unlisting the 'cds' object maps
## the SNPs to the individual cds ranges (vs the concatenated range).
mapToTranscripts(snps[2], unlist(cds))

## The location is the same because the SNP hit the first CDS range. If
## the transcript were on the "-" strand the difference in concatenated
## vs non-concatenated position would be more obvious.

## Change strand:
strand(cds) <- strand(snps) <- "-"
mapToTranscripts(snps[2], unlist(cds))
}

GenomicFeatures documentation built on April 2, 2021, 6 p.m.