rmergeintervalsgenomicrangesiranges

Fast way to find overlaps in linear intervals


I have a data.frame of linear intervals (genomic coordinates of mapped RNA-seq reads), for example:

df <- data.frame(seqnames = c(rep("chr10",2),rep("chr5",8)),
                 start = c(12255935,12257004,12243635,12244009,12253879,12254395,12254506,12255142,12255229,12258719),
                 end = c(12257002,12258512,12243764,12244291,12254107,12254501,12254515,12255535,12255312,12258764),
                 read_id = c(rep("R9",2),rep("R10",8)),
                 stringsAsFactors = F)

For some reads there are intervals that are contained or are intersected within others of the same read, and I'd like to merge them. In the example above for read_id = "R10", interval: chr5 12255229 12255312 is contained within interval chr5 12255142 12255535.

For a single read data.frame, I use this procedure:

#defining helper functions
clusterHits <- function(overlap.hits)
{
  overlap.hits <- GenomicRanges::union(overlap.hits,t(overlap.hits))
  query.hits <- S4Vectors::queryHits(overlap.hits)
  search.hits <- S4Vectors::subjectHits(overlap.hits)
  cluster.ids <- seq_len(S4Vectors::queryLength(overlap.hits))
  while(TRUE){
    hit <- S4Vectors::Hits(query.hits,cluster.ids[search.hits],S4Vectors::queryLength(overlap.hits),S4Vectors::subjectLength(overlap.hits))
    tmp.cluster.ids <- pmin(cluster.ids,S4Vectors::selectHits(hit,"first"))
    if(identical(tmp.cluster.ids,cluster.ids))
      break
    cluster.ids <- tmp.cluster.ids
  }
  unname(S4Vectors::splitAsList(seq_len(S4Vectors::queryLength(overlap.hits)),cluster.ids))
}

mergeConnectedRanges <- function(x.gr,overlap.hits)
{
  cluster.ids <- clusterHits(overlap.hits)
  merged.gr <- range(IRanges::extractList(x.gr,cluster.ids))
  merged.gr <- unlist(merged.gr)
  S4Vectors::mcols(merged.gr)$merged.idx <- cluster.ids
  return(merged.gr)
}

#Now separate R10 and merge its intervals
df1 <- dplyr::filter(df, read_id == "R10")
gr <- GenomicRanges::GRanges(dplyr::select(df1,seqnames,start,end))
redundant.intervals <- GenomicRanges::findOverlaps(gr,ignore.strand=T)
query.gr <- redundant.intervals[S4Vectors::queryHits(redundant.intervals)]
subject.gr <- redundant.intervals[S4Vectors::subjectHits(redundant.intervals)]
as.data.frame(mergeConnectedRanges(x.gr=gr,overlap.hits=redundant.intervals))

Which gives:

  seqnames    start      end width strand merged.idx
1     chr5 12243635 12243764   130      *          1
2     chr5 12244009 12244291   283      *          2
3     chr5 12253879 12254107   229      *          3
4     chr5 12254395 12254501   107      *          4
5     chr5 12254506 12254515    10      *          5
6     chr5 12255142 12255535   394      *       6, 7
7     chr5 12258719 12258764    46      *          8

So the merged.idx shows that intervals 6 and 7 in df1 have been merged.

I'm looking for a fast way of doing this across thousands of reads. The obvious way is to use do.call across the unique reads in df:

library(dplyr)
do.call(rbind, lapply(unique(df$read_id), function(r){
  read.df <- dplyr::filter(df, read_id == r)
  gr <- GenomicRanges::GRanges(dplyr::select(read.df,seqnames,start,end))
  redundant.intervals <- GenomicRanges::findOverlaps(gr,ignore.strand=T)
  query.gr <- redundant.intervals[S4Vectors::queryHits(redundant.intervals)]
  subject.gr <- redundant.intervals[S4Vectors::subjectHits(redundant.intervals)]
  as.data.frame(mergeConnectedRanges(x.gr=gr,overlap.hits=redundant.intervals)) %>%
    dplyr::mutate(read_id = r)
}))

But I'm wondering if there's any faster way. Note that the fraction of reads that actually have such intersecting intervals is relatively small.


Solution

  • Using the GenomicRanges package from the Bioconductor repository, the task can be accomplished by a few lines of code:

    library(GenomicRanges)
    makeGRangesListFromDataFrame(df, split.field = "read_id") |>
      reduce(with.revmap = TRUE) |>
      as.data.frame()
    
      group group_name seqnames    start      end width strand revmap
    1     1        R10     chr5 12243635 12243764   130      *      1
    2     1        R10     chr5 12244009 12244291   283      *      2
    3     1        R10     chr5 12253879 12254107   229      *      3
    4     1        R10     chr5 12254395 12254501   107      *      4
    5     1        R10     chr5 12254506 12254515    10      *      5
    6     1        R10     chr5 12255142 12255535   394      *   6, 7
    7     1        R10     chr5 12258719 12258764    46      *      8
    8     2         R9    chr10 12255935 12257002  1068      *      1
    9     2         R9    chr10 12257004 12258512  1509      *      2
    

    As the GenomeRanges package is not on CRAN, please, see the vignette Installing and Managing Bioconductor Packages or run

    install.packages("BiocManager")
    BiocManager::install("GenomicRanges")
    

    Data

    df <- data.frame(seqnames = c(rep("chr10", 2), rep("chr5", 8)),
                     start = c(12255935, 12257004, 12243635, 12244009, 12253879, 12254395, 12254506, 12255142, 12255229, 12258719),
                     end   = c(12257002, 12258512, 12243764, 12244291, 12254107, 12254501, 12254515, 12255535, 12255312, 12258764),
                     read_id = c(rep("R9", 2), rep("R10", 8)), 
                     stringsAsFactors = FALSE)
    

    As the