PowerPoint Presentation

GIAB WorkshopJanuary 2016

Sub-diffraction-limit resolutionHigher resolution than optical mappingScalableDNA moves through each nanodetector at a velocity of 1 Megabase per secondSemiconductor nature of platform allows for ever-increasing number of nanodetectors per chipSingle-Molecule Electronic Mapping2

Detection regionDetector Schematic3

DetectorDetector Schematic

baseline

templateprobestVEvent measurement(voltage vs. time)Event reporting (distance)Temporal to Spatial Conversion5

Using GIAB Materials6Can we systematically call the existence, type, size, and zygosity of putative SVs?GIAB results for NA12878 are considered a set of positive controls.Negative controls constructed in silico.Apply methodology to putative structural variants in NA24385.

The results demonstrate that it is possible to validate and discover structural variants.

Method7

Construct subsets of the reference genome (GRCh37) that incorporate the putative structural variantMap data to source and to source + appended constructsLook at coverage versus prediction, relative coverage, and interval sizes

GRCh37Variant Reference

GRCh37

Variant Reference8NA12878Chromosome 343,364 bp deletion Deletion With Probe Pattern Change

GRCh37

GRCh37

Variant Reference9NA24385Chromosome 13,926 bp deletion Homozygous Deletion

GRCh37

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10NA24385Chromosome 62,647 bp deletion Heterozygous DeletionExpectedInterval size in GRCh37:4,972 bpDeletion size:2,647 bpInterval size in structural variant:2,325 bp

11Heterozygous DeletionNA24385Chromosome 62,647 bp deletion

Variant ReferenceGRCh37ExpectedMeasuredEOMInterval size in GRCh37:4,972 bp5,005 bp48 bpDeletion size:2,647 bp2,695 bp65 bpInterval size in structural variant:2,325 bp2,310 bp44 bp

12Heterozygous DeletionNA24385Chromosome 7331 bp deletion

Interval size (bp)CountGRCh37Variant ReferenceExpectedMeasuredEOMInterval size in GRCh37:1,968 bp2,060 bp24 bpDeletion size:331 bp566 bp34 bpInterval size in structural variant:1,637 bp1,494 bp24 bp

13GRCh37NA24385Chromosome 7331 bp deletion Heterozygous Deletion

CountInterval size (bp)

13Interval size (bp)CountGRCh37

Data Share/CollaborationData can be used to confirm putative structural variants or for discovery of novel structural variants.Data release to GIAB for NA24385 in the coming weeks.Results of calls on putative structural variants with associated statistics.Data release to collaborators working on SV discovery, validation or de novo assembly:Raw data files, file definitions, software.

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GIAB WorkshopJanuary 2016