Improving the accuracy of variant identification

Deanna M. ChurchNCBI

@deannachurch

Image credit: http://www.tohlejokes.com

ISCA submitted variant: nsv534088

http://www.ncbi.nlm.nih.gov/variation/tools/1000genomes

CDC27

rs11491191

http://www.ncbi.nlm.nih.gov/variation/tools/1000genomes

CEPH: A=1.000 G=0

APOL1

APOL1

YRI: A=0.5852 G=0.4148

Multiple submissions

FrequencyData

1000G

Suspect

Sudmant et al., 2010

APOL1

http://www.ncbi.nlm.nih.gov/variation/tools/1000genomes

http://genomereference.org

nsv832911 (nstd68)Submitted on NCBI35 (hg17)

http://www.ncbi.nlm.nih.gov/dbvar

NCBI35 (hg17) Tiling Path

GRCh37 (hg19) Tiling Path

Gap Inserted

Moved approximately 2 Mb distal on chr15

NC_0000015.8 (chr15)

NC_0000015.9 (chr15)

Removed from assembly

Added to assembly

HG-24

111 Fix PATCHES: Chromosome update in GRCh38

71 Novel PATCHES: Additional sequence added

(adds >5 Mb of novel sequence to the assembly)

(adds >800K of novel sequence to the assembly)

Releasing patches quarterly

GRCh37.p10(160 regions: 2.89% of chromosomes)

Summer of 2013

MHC (chr6)Chr 6 representation (PGF)

Alt_Ref_Locus_2 (COX)

Richa AgarwalaEugene Yaschenko

Dennis et al., 2012

1q32 1q21 1p21

1p21 patch alignment to chromosome 1

http://www.ncbi.nlm.nih.gov/refseq/rsghttp://www.lrg-sequence.org/

http://www.ncbi.nlm.nih.gov/refseq/rsg

RefSeq Gene

L R

http://www.ncbi.nlm.nih.gov/genome/tools/remap

Assembly<->RefSeqGene (including transcripts and coding sequences)

Coordinate Remapping

http://www.ncbi.nlm.nih.gov/genome/tools/remap

NCBI36 <->GRCh37

The Reference Assembly is Evolving

Centralization of assembly and sequence data facilitates:Reporting problemsImplementing fixesBuilding toolsData management

Thanks!

Genome Reference ConsortiumThe Genome Institute at Washington UniversityThe Wellcome Trust Sanger InstituteEuropean Bioinformatics InstituteNational Center for Biotechnology Information

NCBIAssembly GroupRefSeq GroupGenome Annotation Group