Tidy Genomics

Constantin Ahlmann-Eltze

2019-05-27

The most dramatic impact on programming in R the last years was the development of the tidyverse by Hadley Wickham et al. which, combined with the ingenious %>% from magrittr, provides a uniform philosophy for handling data.

The genomics community has an alternative set of approaches, for which bioconductor and the GenomicRanges package provide the basis. The GenomicRanges and the underlying IRanges package provide a great set of methods for dealing with intervals as they typically encountered in genomics.

Unfortunately it is not always easy to combine those two worlds, many common operations in GenomicRanges focus solely on the ranges and loose the additional metadata columns. On the other hand the tidyverse does not provide a unified set of methods to do common set operations with intervals.

At least until recently, when the fuzzyjoin package was extended with the genome_join method for combining genomic data stored in a data.frame. It demonstrated that genomic data could appropriately be handled with the tidy-philosophy.

The tidygenomics package extends the limited set of methods provided by the fuzzyjoin package for dealing with genomic data. Its API is inspired by the very popular bedtools:

genome_intersect

Joins 2 data frames based on their genomic overlap. Unlike the genome_join function it updates the boundaries to reflect the overlap of the regions.

genome_intersect

x1 <- data.frame(id = 1:4, 
                chromosome = c("chr1", "chr1", "chr2", "chr2"),
                start = c(100, 200, 300, 400),
                end = c(150, 250, 350, 450))

x2 <- data.frame(id = 1:4,
                 chromosome = c("chr1", "chr2", "chr2", "chr1"),
                 start = c(140, 210, 400, 300),
                 end = c(160, 240, 415, 320))

genome_intersect(x1, x2, by=c("chromosome", "start", "end"), mode="both")
##   id.x chromosome id.y start end
## 1    1       chr1    1   140 150
## 2    4       chr2    3   400 415

genome_subtract

Subtracts one data frame from the other. This can be used to split the x data frame into smaller areas.

genome_subtract

x1 <- data.frame(id = 1:4,
                chromosome = c("chr1", "chr1", "chr2", "chr1"),
                start = c(100, 200, 300, 400),
                end = c(150, 250, 350, 450))

x2 <- data.frame(id = 1:4,
                chromosome = c("chr1", "chr2", "chr1", "chr1"),
                start = c(120, 210, 300, 400),
                end = c(125, 240, 320, 415))

genome_subtract(x1, x2, by=c("chromosome", "start", "end"))
##   id chromosome start end
## 1  1       chr1   100 119
## 2  1       chr1   126 150
## 3  2       chr1   200 250
## 4  3       chr2   300 350
## 5  4       chr1   416 450

genome_join_closest

Joins 2 data frames based on their genomic location. If no exact overlap is found the next closest interval is used.

genome_join_closest

x1 <- tibble(id = 1:4, 
             chr = c("chr1", "chr1", "chr2", "chr3"),
             start = c(100, 200, 300, 400),
             end = c(150, 250, 350, 450))

x2 <- tibble(id = 1:4,
             chr = c("chr1", "chr1", "chr1", "chr2"),
             start = c(220, 210, 300, 400),
             end = c(225, 240, 320, 415))
genome_join_closest(x1, x2, by=c("chr", "start", "end"), distance_column_name="distance", mode="left")
## # A tibble: 5 x 9
##    id.x chr.x start.x end.x  id.y chr.y start.y end.y distance
##   <int> <chr>   <dbl> <dbl> <int> <chr>   <dbl> <dbl>    <int>
## 1     1 chr1      100   150     2 chr1      210   240       59
## 2     2 chr1      200   250     1 chr1      220   225        0
## 3     2 chr1      200   250     2 chr1      210   240        0
## 4     3 chr2      300   350     4 chr2      400   415       49
## 5     4 chr3      400   450    NA <NA>       NA    NA       NA

genome_cluster

Add a new column with the cluster if 2 intervals are overlapping or are within the max_distance.

genome_cluster

x1 <- data.frame(id = 1:4, bla=letters[1:4],
                chromosome = c("chr1", "chr1", "chr2", "chr1"),
                start = c(100, 120, 300, 260),
                end = c(150, 250, 350, 450))
genome_cluster(x1, by=c("chromosome", "start", "end"))
## # A tibble: 4 x 6
##      id bla   chromosome start   end cluster_id
##   <int> <fct> <fct>      <dbl> <dbl>      <dbl>
## 1     1 a     chr1         100   150          0
## 2     2 b     chr1         120   250          0
## 3     3 c     chr2         300   350          2
## 4     4 d     chr1         260   450          1
genome_cluster(x1, by=c("chromosome", "start", "end"), max_distance=10)
## # A tibble: 4 x 6
##      id bla   chromosome start   end cluster_id
##   <int> <fct> <fct>      <dbl> <dbl>      <dbl>
## 1     1 a     chr1         100   150          0
## 2     2 b     chr1         120   250          0
## 3     3 c     chr2         300   350          1
## 4     4 d     chr1         260   450          0

genome_complement

Calculates the complement of a genomic region.

genome_complement

x1 <- data.frame(id = 1:4,
                 chromosome = c("chr1", "chr1", "chr2", "chr1"),
                 start = c(100, 200, 300, 400),
                 end = c(150, 250, 350, 450))

genome_complement(x1, by=c("chromosome", "start", "end"))
## # A tibble: 4 x 3
##   chromosome start   end
##   <fct>      <int> <int>
## 1 chr1           1    99
## 2 chr1         151   199
## 3 chr1         251   399
## 4 chr2           1   299

genome_join

Classical join function based on the overlap of the interval. Implemented and mainted in the fuzzyjoin package and documented here only for completeness.

genome_join

x1 <- tibble(id = 1:4, 
             chr = c("chr1", "chr1", "chr2", "chr3"),
             start = c(100, 200, 300, 400),
             end = c(150, 250, 350, 450))

x2 <- tibble(id = 1:4,
             chr = c("chr1", "chr1", "chr1", "chr2"),
             start = c(220, 210, 300, 400),
             end = c(225, 240, 320, 415))
fuzzyjoin::genome_join(x1, x2, by=c("chr", "start", "end"), mode="inner")
## # A tibble: 2 x 8
##    id.x chr.x start.x end.x  id.y chr.y start.y end.y
##   <int> <chr>   <dbl> <dbl> <int> <chr>   <dbl> <dbl>
## 1     2 chr1      200   250     1 chr1      220   225
## 2     2 chr1      200   250     2 chr1      210   240
fuzzyjoin::genome_join(x1, x2, by=c("chr", "start", "end"), mode="left")
## # A tibble: 5 x 8
##    id.x chr.x start.x end.x  id.y chr.y start.y end.y
##   <int> <chr>   <dbl> <dbl> <int> <chr>   <dbl> <dbl>
## 1     1 chr1      100   150    NA <NA>       NA    NA
## 2     2 chr1      200   250     1 chr1      220   225
## 3     2 chr1      200   250     2 chr1      210   240
## 4     3 chr2      300   350    NA <NA>       NA    NA
## 5     4 chr3      400   450    NA <NA>       NA    NA
fuzzyjoin::genome_join(x1, x2, by=c("chr", "start", "end"), mode="anti")
## # A tibble: 3 x 4
##      id chr   start   end
##   <int> <chr> <dbl> <dbl>
## 1     1 chr1    100   150
## 2     3 chr2    300   350
## 3     4 chr3    400   450