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For human data, using human NGS reads (1.4GB) as GRanges:
# Using reduced data that has a score column for duplicated reads,
# every unique read is only once.
system.time(withWeights <- coverageByTranscript(a, cds, weight = "score"))
user system elapsed
3.987 0.683 4.667
# Using raw data, without reducing the data-set by not creating
# a $score column for number of duplicated reads
> system.time(withoutWeights <- coverageByTranscript(b, cds))
user system elapsed
37.956 21.586 59.547
> identical(d, dd)
[1] TRUE
I just changed the coverageByTranscript function to allow weights, maybe a possible improvement?