On 03/16/2015 09:22 AM, Michael Lawrence wrote:
Yes, I think it would make sense for the Xtra package to follow the established convention in VariantAnnotation/VCF.
I don't know. I agree it would be nice to use a more consistent representation of insertions across the software but I'm not convinced we should necessarily follow the VCF way, which is to include the base before the event in the ref and alt alleles as well as in the reported range. Note that there doesn't seem to be any consensus in the broader Bioinformatics community either. For example dbSNP and HGVS report the range that corresponds to the 2 flanking nucleotides but they don't include these nucleotides in the ref or alt alleles. VCF does the same as GFF3 which says "start equals end and the implied site is to the right of the indicated base" except that VCF wants to treat events that occur at position 1 in a special way. In that case VCF says the base *after* the event should be included (seems like the VCF authors want to avoid both: empty ranges and also ranges that start at POS 0). BTW it doesn't seem that VariantAnnotation::isInsertion() is aware of that special treatment. UCSC uses a zero-width range, and so does the XtraSNPlocs.* packages. The advantage of this representation is its simplicity. There is no special cases. It also reflects the notion that an insertion is a replacement of an empty string with a non-empty string. No need to include flanking nucleotides in the representation (which is artificial and distorts the "real" alt allele). H.
On Mon, Mar 16, 2015 at 9:16 AM, Robert Castelo <robert.cast...@upf.edu> wrote:dear devel people, specially Val and Michael, Hervé has recently added an annotation package that includes non-SNVs variants from dbSNP, it is called: library(XtraSNPlocs.Hsapiens.dbSNP141.GRCh38) if you execute the corresponding example you'll see the kind of information stored in the package: example(XtraSNPlocs.Hsapiens.dbSNP141.GRCh38) if you pay attention to the following case: my_snps1[1:2] GRanges object with 2 ranges and 3 metadata columns: seqnames ranges strand | RefSNP_id alleles <Rle> <IRanges> <Rle> | <character> <character> [1] 22 [10513380, 10513380] - | rs386831164 -/T [2] 22 [10519678, 10519677] + | rs71286731 -/TTT ref_allele <DNAStringSet> [1] T [2] - ------- seqinfo: 25 sequences (1 circular) from GRCh38 genome you'll see the first variant (rs386831164) is a deletion of one nucleotide and the second (rs71286731) is an insertion of three nucleotides (TTT). it struck me that the ranges representing the insertion had an start position one nucleotide larger than then and i contacted Hervé thinking that this was a mistake. however, i've learned from him that these are so-called "zero-width" ranges and they actually allow to distinguish insertions from every other type of variant without the need to know anything about the reference or the alternate allele. currently, the VCF specification 4.2 (http://samtools.github.io/ hts-specs/VCFv4.2.pdf page 5) uses the nucleotide composition of the REF column to help distinguishing insertions by including the flanking nucleotide of the inserted sequence. As a result, VariantAnnotation::readVcf() produces ranges that mimic this standard having identical start and end positions leading to 1-width ranges: fl <- system.file("extdata", "CEUtrio.vcf.bgz", package="VariantFiltering") vcf <- readVcf(fl, genome="hg19") rowRanges(vcf[isInsertion(vcf), ])[1:2] GRanges object with 2 ranges and 5 metadata columns: seqnames ranges strand | paramRangeID <Rle> <IRanges> <Rle> | <factor> rs11474033 20 [45093330, 45093330] * | <NA> 20:47592746_G/GGC 20 [47592746, 47592746] * | <NA> REF ALT QUAL FILTER <DNAStringSet> <DNAStringSetList> <numeric> <character> rs11474033 C CTTCT 2901.12 . 20:47592746_G/GGC G GGC 608.88 . ------- seqinfo: 84 sequences from hg19 genome table(width(rowRanges(vcf[isInsertion(vcf), ]))) 1 78 i would like to ask whether it would make sense to harmonize the way in which dbSNP insertions and variants are imported into Bioconductor by making VariantAnnotation::readVcf() to produce zero-width ranges for insertion variants. this not a feature request, i only would like to know what whether there is a particular reason not to use the available zero-width ranges that seem to be implemented for this purpose. cheers, robert. _______________________________________________ Bioc-devel@r-project.org mailing list https://stat.ethz.ch/mailman/listinfo/bioc-devel[[alternative HTML version deleted]] _______________________________________________ Bioc-devel@r-project.org mailing list https://stat.ethz.ch/mailman/listinfo/bioc-devel
-- Hervé Pagès Program in Computational Biology Division of Public Health Sciences Fred Hutchinson Cancer Research Center 1100 Fairview Ave. N, M1-B514 P.O. Box 19024 Seattle, WA 98109-1024 E-mail: hpa...@fredhutch.org Phone: (206) 667-5791 Fax: (206) 667-1319 _______________________________________________ Bioc-devel@r-project.org mailing list https://stat.ethz.ch/mailman/listinfo/bioc-devel
