Improvement of variant calling in next-generation sequence data requires
a comprehensive, genome-wide catalog of high-confidence variants called in
a set of genomes for use as a benchmark. We generated deep, whole-genome
sequence data of 17 individuals in a three-generation pedigree and called
variants in each genome using a range of currently available algorithms.
We used haplotype transmission information to create a phased "Platinum"
variant catalog of 4.7 million single-nucleotide variants (SNVs)
plus 0.7 million small (1-50 bp) insertions and deletions (indels) that are
consistent with the pattern of inheritance in the parents and 11 children
of this pedigree. Platinum genotypes are highly concordant with the current
catalog of the National Institute of Standards and Technology for
both SNVs (>99.99%) and indels (99.92%) and add a validated truth catalog
that has 26% more SNVs and 45% more indels. Analysis of 334,652 SNVs that
were consistent between informatics pipelines yet inconsistent with haplotype
transmission ("nonplatinum") revealed that the majority of these variants
are de novo and cell-line mutations or reside within previously unidentified
duplications and deletions. The reference materials from this study are a
resource for objective assessment of the accuracy of variant calls
The 'hybrid' truthsets were generated by merging Genome in a Bottle
high confidence calls (hg001, v3.3.2) with those from the Platinum
Genomes truthset for the same sample (NA12878, v2017-1.0). Merged
records were validated by performing a k-mer test on alignments from
the lower pedigree CEPH 1463 (11 children). Records with k-mer support
via haplotype inheritance were added to the hybrid truthset.
The VCF files for this track can be obtained from the download server:
These files were obtained from the Platinum genomes source archive:
Eberle MA, Fritzilas E, Krusche P, Källberg M, Moore BL, Bekritsky MA, Iqbal Z, Chuang HY,
Humphray SJ, Halpern AL et al.
A reference data set of 5.4 million phased human variants validated by genetic inheritance from
sequencing a three-generation 17-member pedigree.
Genome Res. 2017 Jan;27(1):157-164.
PMID: 27903644; PMC: PMC5204340