[Bioc-devel] Extending Views to support GRanges (and possibly BigWig files)

[Johnston, Jeffrey]

During the BioC developer day, Hervé brought up the idea of possibly extending the concept of GenomicViews to other use cases. I'd like to share how we currently use GenomicRanges, Views and RleLists to perform certain analyses, and hopefully demonstrate that a way to directly use Views with GRanges would be quite useful.

As an example, let's say we have 2 ChIP-seq samples (as BigWig files) and a set of genomic ranges we are interested in (as a BED file). We want to find the sum of the ChIP-seq signal found in our regions of interest for each of the two samples. We'd first import the BED file as a GRanges object. Annotating the GRanges with two metadata columns representing the ChIP-seq signal for the two samples seems like a straightforward use for Views (in particular, viewSums), but it is a bit convoluted.

The main problem is that Views work with RangesLists, not GRanges. Coercing a GRanges to a RangesList possibly disrupts the order, so we have to first reorder the GRanges to match the order it will be given after coercion (keeping track so we can later revert back to the original order):

regions <- import("regions_of_interest.bed")
sample1_cov <- import("sample1.bw", as="RleList")
sample2_cov <- import("sample2.bw", as="RleList")
oo <- order(regions)
regions <- regions[oo]

Now we can construct a View and use viewSums to obtain our values (unlisting them as they are grouped by seqnames) and add them as a metadata column in our GRanges, restoring the original order of the GRanges when we are done:

v <- Views(sample1_cov, as(regions, "RangesList"))
mcols(regions)$sample1_signal <- unlist(viewSums(v))
regions[oo] <- regions

We then repeat the process to add another metadata column for sample2.

To me, having the ability to use a GRanges as a view into an RleList makes a lot more sense. That would allow us to reduce all the above complexity to something like:

regions$sample1_signal <- viewSums(Views(sample1_cov, regions))
regions$sample2_signal <- viewSums(Views(sample2_cov, regions))

That alone would be great! But, there's a way to make it even better. Storing these RleLists in memory for each of our samples is quite inefficient, especially since our regions of interest are only a small portion of them. The rtracklayer package already has some very useful functionality for instantiating an RleList with only the data from specific ranges of a BigWig file. Taking advantage of that, we can dramatically reduce our memory usage and increase our performance like so:

regions <- import("regions_of_interest.bed")
sample1_cov <- import("sample1.bw", as="RleList", which=regions)
sample2_cov <- import("sample2.bw", as="RleList", which=regions)
regions$sample1_signal <- viewSums(Views(sample1_cov, regions))
regions$sample2_signal <- viewSums(Views(sample2_cov, regions))

But can't this functionality be included in Views? Why not have it accept a BigWig file in place of an RleList and have it selectively load the portions of the BigWig it needs based on the provided GRanges? That would allow this:

regions <- import("regions_of_interest.bed")
regions$sample1_signal <- viewSums(Views("sample1.bw", regions))
regions$sample2_signal <- viewSums(Views("sample2.bw", regions))

The above is quite close to how I use GRanges and BigWigs now, except I have to write and maintain all the hackish code to link BigWig files, GRanges, Views, RangesLists and RleLists together into something that behaves as one would intuitively expect.

I’d welcome any thoughts on how people perform similar analyses that involve GRanges and data stored in BigWig files or RleLists, and whether this would also be useful to them.

Thanks,
Jeff Johnston
Zeitlinger Lab
Stowers Institute