Aug2015 analysis team spiral genetics

ANCHORED ASSEMBLYAccurate Structural Variant Detection Using Short-Read Data

AA

Bruestle, J.J. and Shekar, S.N.

Methodology

Anchoring

AA

Anchor Assemblies

7 7 7

7

8 89 9

7

8

7

R1 R2

R3 R5

R8R7

R3 R6 R9

Read overlapassembly

Read Overlap Assembly

Remove Reference ReadsRead Correction

0

0 200 400 600 800 1000 1200

1000

2000

3000

4000

5000

K-m

er C

ount

Total K-mer Quality Score

K-mer Quality Score Distribution

A* error correction

SV Comparison

Baylor College of Medicine, against Illumina, PacBio, Array, Nextera and BioNano

Program FDR Sensitivity

CNVnator 80.46% 22.62%

BreakDancer 58.89% 42.39%

Delly 55.13% 31.18%

Crest 14.87% 35.29%

Pindel 31.81% 56.70%

SVStat 1.79% 16.36%

Tiresias 69.04% 7.79%

Spiral 3.03% 42%

English et al. (2015), updated

AA

Fosmid/PacBio validated SVsAA

Validated in collaboration by Malig, M, Eichler, EE et al.

Selected 15 high confidence SVs not previously detected in the 1000 Genomes Project

PacBio validated SVs deleteAA

Chr Call Size (bp) Clones seq with PacBio

Validated by Micropeats

Validated by Dotplots

Call validated?

1 1026 2 2 2 yes

1 6375 2 2 2 yes

2 26838 2 2 2 yes

3 4184 1 1 1 yes

5 9507 2 2 2 yes

7 3013 1 1 1 yes

8 5157 2 1 1 yes

9 2883 1 1 1 yes

15 6051 2 2 2 yes

Malig, M, Eichler, EE et al. (Manuscript in preparation)

PacBio validated SVs InsertsAA


Chr Call Size (bp) Clones seq with PacBio

Validated by Micropeats

Validated by Dotplots

Call validated?

1 1755 2 2 2 yes

1 3865 2 2 2 yes

8 2457 2 2 2 yes

8 1508 2 2 2 yes

13 2142 2 2 2 yes

X 1548 2 2 2 yes

PacBio validation dotplotsAA


Chromosome 1

3.8kb insertion

Chromosome 1

6.4kb deletion



Chromosome 2

26.8kb deletion



Ashkenazi Jewish Trio AA

Validated by Noah Spies using his program SV Viz

Chr2 Deletion Chr8 Insertion

Reference

Chr 2 Deletion - FatherAA

Alternative

Chr 2 Deletion - MotherAA

Alternative

Reference

Chr 2 Deletion - OffspringAA

Alternative

Reference

Chr 2 Deletion - VCF IdenticalAA

HG002 - Offspring chr2 34695829 T <DEL> 100 PASS NS=1;DP=51;SVTYPE=DEL;END=34736567;SVLEN=-40730 DP:AD 51:21,30

HG003 - Father chr2 34695829 T <DEL> 100 PASS NS=1;DP=55;SVTYPE=DEL;END=34736567;SVLEN=-40730; DP:AD 55:0,55

Chr 8 Insertion - FatherAA

Alternative

Reference

Chr 8 Insertion - MotherAA

Alternative

Reference

Chr 8 Insertion - OffspringAA

Alternative

Reference

HG0004

chr8 129739066 AATAAA 100 masking_present NS=1;DP=41;SVTYPE=INS; END=129739071;SVLEN=3404; DP:AD 41:28,13

Chr 2 Insertion - VCF IdenticalAA

GAAAGTTGTGCACAATATAAAAATTATAATTTTATATTTCAAAACAAATTAAATATCTTAAAATTATAGAAGACATTAAAGAACTATATAAATCAAAGTTAGAAAAAAACCCAGATGTGAGTTGGGAAATCTGAAGAAAATTTAAAAGAGAAATTTAAAAATATTAATATAAAAAATGAAGACTAAACTGGAAAGATACACTAGAGTGAATAAACAAAATAGAAAATACTCAGATGTTTTGTTTTAACTTCCTATTGTATGAGTTTTGGAGACCAACATAAGATAATGACTTGCCTCTGGATATGAAGGTAAAAAAACAGACACAGGCCTATGTAGTGATTTCTTACAGAACAACACAGCAGAAAGCAAATCCCTAAAAAACCATGTGGACGTGGCTTTTACAGATGGTTGTCCAATCCCTGCATGCTATTGCTTGCTTATGGATGAGTGAAAGGAATAAAAATTTTAAGTTATAGCTACAGTTTCTCTACCTGTACATTCCAATACTGACCTTGCATGGTTTCTTTGAGGGCTAAGTATGACAAAAGGATGCAGTGATTTCGAACTTAGATTTTAAAAAACAAATATGACTCTTTTGAACTGTGTGAACATAGGCACATTGCTGGATCTGAGTAATTTCATGTGCTAAGAGGGAATAATAGCATCAGCCTTAATGCTGCATTATTGCATTTAGCATTATTTCTTTCTGAAGATGAAAGAAGACAGACATCATTATATTTAACAAAGTGCCTGGCACATATAAAATAGTCAATAAATGTTATCTATCATTGCTATTATTACCTAATACTGCGCATAGTAAGCCCTGAACCTGTTCCTGGCATGTGGAGCTATGTACTATGTTCATGACATTAAACAAAGTAGTAGCTATATAATGAATATATAAATGTGACTTTTATTATTACATCCCTGTAGTTTTGGCAAGTAGTTTACTAAAAGGAAGTTCCAATTTTGACTTAGCATGGAGTTTGTTTTTATCCTGGGCATGTTATCTACCCAGCTTACCTTATTCTTCCTTTCTTCGAAACAGGAATCATGCTTGTTAATTGACTGGGATGTTGCAAGGCCTTATATCTGAGAAGTATATCATCAAGGAATAGAGAAGATGAGGCTTAGAGAGGAAATGGAAGCCCCTGTCAATTAGGAGAGGCAAAGGCTCTATGATACAGCATAGCCTAAGAATTTCGTTGATACAGAATTCTAAGTGTGAAACGAATGAATGGAGTGACCACTCCTCCCTACTAAAGAATCTTGTAAACACTAGTTTTAAAAGCACAAACGTATTATATCATATACCTATGTATAATGTCATTTTGCTACTTTTCTCTTCCAACTTCTCAAATCTTTGAATGCAGGGGTTTTTGGAGTTATTCCCTGTGTATTATTTCGACTGATATGTAATAGCTGCTCAGCGAATGTGTGTTGCTAAATAAGAGATGGAGTACAGACAAGCTGAAATTGCACATTTATGTTGCCATTGTACTGCTCAAAAAAAAAAAAAATTAGAATTAGGGTTAAAGAGAGTGCTCAGGCCCTAGACTAGGATTTATTTGCTGTATAATAAACTTTATGCAAACAATTAACCTCCCTGCTTCTCAATTTTCTCCTCTATAAAATTGGGTTATTACAAAATTCTTTGTAACATATTATGGAGTTCAATTAGGATAAGTTAAATATTGGAAATCTGAAGCATTATGCAAATATGAGGCATTATTATAATAATTATAACAATATTGTTTTTATTCTTAATTGCTACTCTTGAGTACTCTGTTGCTCTGCAGATATCTCTCTCCCTGCCTTCCCCAGGGTGTTGGCATACCAGGATGCCTCTTTAGAAAAGAAATTGCACGATGGACCTAAGGAAACAGAATTTTCCATCCTGGCATTTGCATAAAGGCCACACATGCATAGCCATATGCTGATTTAACCAACAGCTTTCACACTTATAATCGAGTTTGCTACTTGTTCTGCGATATCTACTCTCCCTCTATTTCTTATTAATAGAACAAAATTTTAGTTGGGAATATGGCTACTGAGAATAAAGATTACCTTTCTCAGCTTCTTTGCGGCTAACTCTGATTATGTGTCTAAACTTTGGTGCATATTTTGGTAAACGGAAATTCTTAAAGGGAGATTCTCTACTTTCTTCCTGCTTGCTGGAATGCAAACATGATTGTTGGATTTGAGCAGCCATCTTATGCCAGGAGTTGGAAACCATGCAGGCAGATCCTGGTCATTAGCACTACAGACCTCTATACCAAACTGGATTTCTGTGAGACTCCAGAAGAAAGTAAGCAGCACAAGGAGTTTCTTCATGTATTCTTCATTTCCCACACCCCATTATACGTGCTTTTGCTGTAATCTGGAATCAGTTGTACTAATCTACTGCACATACCTAGATTCTATTGATAGTCTATTCCAGGATTGATAACTTTGAGCCCAGATAACTTGCAGTAAGATTTATAACAAGATTTCAAAAATATTCTTTCCTATACACCAAATAGTTTTGGTTAGAGAAAACAAAACTTTTGGCATAGCAACTTCATTTGTAGGAAGTTACCTTCTTAAAATTGTTTATCTGTGGACAGCTATGCTGCTATTAGTAGGGAATGGTTTCAGGCAAAAGGTTACAGAAGGATGGAGAGGGCCTGGGCTTTGGGGTTCCAGGGGTATGGAAGTCAGCAGAGCTGAGAGTAGTTCCCAACAGCCAGAGTGTCCATGGATCAAGCCCTTTTGTGAAGCTGGAGGTACCAGCGCTGGTCCAGGATGCGCAGCTGTAAAGTTGTGAATATATGTATTTGGTCTTTTTCCTTGTTTGCTGGCCTACAACTCTTAAAATCCTTGGAATCTTCAAAGTGATGTGTCTTTTTGTATGCTAATGAGTTGACTAATGGCTGGCAGCCTCTAGGTGGCTTCTGGATAAGAGCTGGTCACCAGGAAGACCAAGGCCAGATTAGAGGGTTGGGACATTCGGTCCTACTCCGCAACCACCATGGAGACAGTCTGAAGGTTAACTTGATCACCAATGGCCAATAATTTCATCAATCATGCCAGTGTAATGAAGCCAGCATAAAAACTCAAAAGGACAGGGCTCAGAGAGTTCCATTAGCTGAACATTGGAGGTTCCCACAAGTGGCATGCCCGGAGGGGGTTATGGAAGCTTCACACCCTTTCCCCATACCTCACCCTGTGCATCTCTTCATCTGTATCTTCTGTAATATCCTTTATAATACGCCATTAAATATAAGGAAGTATTTCTCTGAGTTCTGTGAGCCACTCTACCACATTAATCGAACCCCATGGGGAAGCTGAGTAAAGTTTCAAGTGGAGTAAAATTGCTGATACCGTGACCATCAGGTCAATGTTGCTGGAAGCACAGGTAAAACAAACT

Mother

GAAAGTTGTGCACAATATAAAAATTATAATTTTATATTTCAAAACAAATTAAATATCTTAAAATTATAGAAGACATTAAAGAACTATATAAATCAAAGTTAGAAAAAAACCCAGATGTGAGTTGGGAAATCTGAAGAAAATTTAAAAGAGAAATTTAAAAATATTAATATAAAAAATGAAGACTAAACTGGAAAGATACACTAGAGTGAATAAACAAAATAGAAAATACTCAGATGTTTTGTTTTAACTTCCTATTGTATGAGTTTTGGAGACCAACATAAGATAATGACTTGCCTCTGGATATGAAAGTAAAAAAACAGACACAGGCCTATGTAGTGATTTCTTACAGAACAACACAGCAGAAAGCAAATCCCTAACAAACCATGTGGACGTGGCTTTTACAGATGGTTGTCCAATCCCTGCATGCTATTGCTTGCTTATGGATGAGTGAAAGGAATAAAAATTTTAAGTTATAGCTACAGTTTCTCTACCTGTACATTCCAATACTGACCTTGCATGGTTTCTTTGAGGGCTAAGTATGACAAAAGGATGCAGTGATTTCGAACTTAGATTTTAAAAAACAAATATGACTCTTTTGAACTGTGTGAACATAGGCACATTGCTGGATCTGAGTAATTTCATGTGCTAAGAGGGAATAATAGCATCAGCCTTAATGCTGCATTATTGCATTTAGCATTATTTCTTTCTGAAGATGAAAGAAGACAGACATCATTATATTTAACAAAGTGCCTGGCACATATAAAATAGTCAATAAATGTTATCTATCATTGCTATTATTACCTAATACTGCGCATAGTAAGCCCTGAACCTGTTCCTGGCATGTGGAGCCATGTACTATGTTCATGACATTAAACAAAGTAGTAGCTATATAATGAATATATAAATGTGACTTTTATTATTACATCCCTGTAGTTTTGGCAAGTAGTTTACTAAAAGGAAGTTCCAATTTTGACTTAGCATGGAGTTTGTTTTTATCCTGGGCATGTTATCTACCCAGCTTACCTTATTCTTCCTTTCTTCGAAACAGGAATCATGCTTGTTAATTGACTGGGATGTTGCAAGGCCTTATATCTGAGAAGTATATCATCAAGGAATAGAGAAGATGAGTCTTAGAGAGGAAATGGAAGCCCCTGTCAATTAGGAGAGGCAAAGGCTCTATGATACAGCATAGCCTAAGAATTTCGTTGATACAGAATTCTAAGTGTGAAACGAATGAATGGAGTGACCACTCCTCCCTACTAAAGAATCTTGTAAACACTAGTTTTAAAAGCACAAACGTATTATATCATATACCTATGTATAATGTCATTTTGCTACTTTTCTCTTCCAACTTCTCAAATCTTTGAATGCAGGGGTTTTTGGAGTTATTCCCTGTGTATTATTTCGACTGATATGTAATAGCTGCTCAGCGAATGTGTGTTGCTAAATAAGAGATGGAGTACAGACAAGCTGAAATTGCACATTTATGTTGCCATTGTACTGCTCAAAAAAAAAAAAAAATTAGAATTAGGGTTAAAGAGAGTGCTCAGGCCCTAGACTAGGATTTATTTGCTGTATAATAAACTTTATGCAAACAATTAACCTCCCTGCTTCTCAATTTTCTCCTCTATAAAATTGGGTTATTACAAAATTCTTTGTAACATATTATGGAGTTCAATTAGGATAAGTTAAATATTGGAAATCTGAAGCATTATGCAAATATGAGGCATTATTATAATAATTATAACAATATTGTTTTTATTCTTAATTGCTACTCTTGAGTACTCTGTTGCTCTGCAGATATCTCTCTCCCTGCCTTCCCCAGGGTGTTGGCATACCAGGATGCCTCTTTAGAAAAGAAATTGTACGATCGACCTAAGGAAACAGAATTTTCCATCCTGGCATTTGCATAAAGGCCACACATGCATAGCCATATGCTGATTTAACCAACAGCTTTCACACTTATAATCGAGTTTGCTACTTGTTCTGCGATATCTACTCTCCCTCTATTTCTTATTAATAGAACAAAATTTTAGTTGGGAATATGGCTACTGAGAATAAAGATTACCTTTCTCAGCTTCTTTGCGGCTAACTCTGATTATGTGTCTAAACTTTGGTGCATATTTTGGTAAACGGAAATTCTTAAAGGGAGATTCTCTACTTTCTTCCTGCTTGCTGGAATGCAAACATGATTGTTGGATTTGAGCAGCCATCTTATGCCAGGAGTTGGAAACCATGCAGGCAGATCCTGGTCATTAGCACTACAGACCTCTATACCAAACTGGATTTCTGTGAGACTCCAGAAGAAAGTAAGCAGCACAAGGAGTTTCTTCATGTATTCTTCATTTCCCACACCCCATTATACGTGCTTTTGCTGTAATCTGGAATCAGTTGTACTAATCTACTGCACATACCTAGATTCTATTGATAGTCTATTCCAGGATTGATAACTTTGAGCCCAGATAACTTGCAGTAAGATTTATAACAAGATTTCAAAAATATTCTTTCCTATACACCAAATAGTTTTGGTTAGAGAAAACAAAACTTTTGGCATAGCAACTTCATTTGTAGGAAGTTACCTTCTTAAAATTGTTTATCTGTGGACAGCTATGCTGCTATTAGTAGGGAATGGTTTCAGGCAAGAGGTTACAGAAGGATGGAGAGGGCCTGGGCTTTGGGGTTCCAGGGGTATGGAAGTCAGCAGAGCTGAGAGTAGTTCCCAACAGCCAGAGTGTCCATGGATCAAGCCCTTTTGTGAAGCTGGAGGTACCAGCGCTGGTCCAGGATGCGCAGCTGTAAAGTTGTGAATATATGTATTTGGTCTTTTTCCTTGTTTGCTGGCCTACAACTCTTAAAATCCTTGGAATCTTCAAAGTGATGTGTCTTTTTGTATGCTAATGAGTTGACTAATGGCTGGCAGCCTCTAGGTGGCTTCTGGATAAGAGCTGGTCACCAGGAAGACCAAGGCCAGATTAGAGGGTTGGGACATTCGGTCCTACTCCGCAACCACCATGGAGACAGTCTGAAGGTTAACTTGATCACCAATGGCCAATAATTTCATCAATCATGCCAGTGTAATGAAGCCAGCATAAAAACTCAAAAGGACAGGGCTCAGAGAGTTCCATTAGCTGAACATTGGAGGTTCCCACAAGTGGCATGCCCGGAGGGGGTTATGGAAGCTTCACACCCTTTCCCCATACCTCACCCTGTGCATCTCTTCATCTGTATCTTCTGTAATATCCTTTATAATACGCCATTAAATATAAGGAAGTATTTCTCTGAGTTCTGTGAGCCACTCTACCACATTAATCGAACCCCATGGGGAAGCTGAGTAAAGTTTCAAGTGGAGTAAAATTGCTGATACCGTGACCATCAGGTCAATGTTGCTGGAAGCACAGGTAAAACAACCT


FatherHG003

chr8 129739066 AATAAA 100 masking_present NS=1;DP=47;SVTYPE=INS; END=129739071;SVLEN=3405;DP:AD 47:32,15


HG002

chr8 129739066 AATAAA 100 masking_present NS=1;DP=18;SVTYPE=INS; END=129739071;SVLEN=3405;DP:AD 18:0,18

GAAAGTTGTGCACAATATAAAAATTATAATTTTATATTTCAAAACAAATTAAATATCTTAAAATTATAGAAGACATTAAAGAACTATATAAATCAAAGTTAGAAAAAAACCCAGATGTGAGTTGGGAAATCTGAAGAAAATTTAAAAGAGAAATTTAAAAATATTAATATAAAAAATGAAGACTAAACTGGAAAGATACACTAGAGTGAATAAACAAAATAGAAAATACTCAGATGTTTTGTTTTAACTTCCTATTGTATGAGTTTTGGAGACCAACATAAGATAATGACTTGCCTCTGGATATGAAGGTAAAAAAACAGACACAGGCCTATGTAGTGATTTCTTACAGAACAACACAGCAGAAAGCAAATCCCTAAAAAACCATGTGGACGTGGCTTTTACAGATGGTTGTCCAATCCCTGCATGCTATTGCTTGCTTATGGATGAGTGAAAGGAATAAAAATTTTAAGTTATAGCTACAGTTTCTCTACCTGTACATTCCAATACTGACCTTGCATGGTTTCTTTGAGGGCTAAGTATGACAAAAGGATGCAGTGATTTCGAACTTAGATTTTAAAAAACAAATATGACTCTTTTGAACTGTGTGAACATAGGCACATTGCTGGATCTGAGTAATTTCATGTGCTAAGAGGGAATAATAGCATCAGCCTTAATGCTGCATTATTGCATTTAGCATTATTTCTTTCTGAAGATGAAAGAAGACAGACATCATTATATTTAACAAAGTGCCTGGCACATATAAAATAGTCAATAAATGTTATCTATCATTGCTATTATTACCTAATACTGCGCATAGTAAGCCCTGAACCTGTTCCTGGCATGTGGAGCTATGTACTATGTTCATGACATTAAACAAAGTAGTAGCTATATAATGAATATATAAATGTGACTTTTATTATTACATCCCTGTAGTTTTGGCAAGTAGTTTACTAAAAGGAAGTTCCAATTTTGACTTAGCATGGAGTTTGTTTTTATCCTGGGCATGTTATCTACCCAGCTTACCTTATTCTTCCTTTCTTCGAAACAGGAATCATGCTTGTTAATTGACTGGGATGTTGCAAGGCCTTATATCTGAGAAGTATATCATCAAGGAATAGAGAAGATGAGTCTTAGAGAGGAAATGGAAGCCCCTGTCAATTAGGAGAGGCAAAGGCTCTATGATACAGCATAGCCTAAGAATTTCGTTGATACAGAATTCTAAGTGTGAAACGAATGAATGGAGTGACCACTCCTCCCTACTAAAGAATCTTGTAAACACTAGTTTTAAAAGCACAAACGTATTATATCATATACCTATGTATAATGTCATTTTGCTACTTTTCTCTTCCAACTTCTCAAATCTTTGAATGCAGGGGTTTTTGGAGTTATTCCCTGTGTATTATTTCGACTGATATGTAATAGCTGCTCAGCGAATGTGTGTTGCTAAATAAGAGATGGAGTACAGACAAGCTGAAATTGCACATTTATGTTGCCATTGTACTGCTCAAAAAAAAAAAAAAATTAGAATTAGGGTTAAAGAGAGTGCTCAGGCCCTAGACTAGGATTTATTTGCTGTATAATAAACTTTATGCAAACAATTAACCTCCCTGCTTCTCAATTTTCTCCTCTATAAAATTGGGTTATTACAAAATTCTTTGTAACATATTATGGAGTTCAATTAGGATAAGTTAAATATTGGAAATCTGAAGCATTATGCAAATATGAGGCATTATTATAATAATTATAACAATATTGTTTTTATTCTTAATTGCTACTCTTGAGTACTCTGTTGCTCTGCAGATATCTCTCTCCCTGCCTTCCCCAGGGTGTTGGCATACCAGGATGCCTCTTTAGAAAAGAAATTGCACGATGGACCTAAGGAAACAGAATTTTCCATCCTGGCATTTGCATAAAGGCCACACATGCATAGCCATATGCTGATTTAACCAACAGCTTTCACACTTATAATCGAGTTTGCTACTTGTTCTGCGATATCTACTCTCCCTCTATTTCTTATTAATAGAACAAAATTTTAGTTGGGAATATGGCTACTGAGAATAAAGATTACCTTTCTCAGCTTCTTTGCGGCTAACTCTGATTATGTGTCTAAACTTTGGTGCATATTTTGGTAAACGGAAATTCTTAAAGGGAGATTCTCTACTTTCTTCCTGCTTGCTGGAATGCAAACATGATTGTTGGATTTGAGCAGCCATCTTATGCCAGGAGTTGGAAACCATGCAGGCAGATCCTGGTCATTAGCACTACAGACCTCTATACCAAACTGGATTTCTGTGAGACTCCAGAAGAAAGTAAGCAGCACAAGGAGTTTCTTCATGTATTCTTCATTTCCCACACCCCATTATACGTGCTTTTGCTGTAATCTGGAATCAGTTGTACTAATCTACTGCACATACCTAGATTCTATTGATAGTCTATTCCAGGATTGATAACTTTGAGCCCAGATAACTTGCAGTAAGATTTATAACAAGATTTCAAAAATATTCTTTCCTATACACCAAATAGTTTTGGTTAGAGAAAACAAAACTTTTGGCATAGCAACTTCATTTGTAGGAAGTTACCTTCTTAAAATTGTTTATCTGTGGACAGCTATGCTGCTATTAGTAGGGAATGGTTTCAGGCAAAAGGTTACAGAAGGATGGAGAGGGCCTGGGCTTTGGGGTTCCAGGGGTATGGAAGTCAGCAGAGCTGAGAGTAGTTCCCAACAGCCAGAGTGTCCATGGATCAAGCCCTTTTGTGAAGCTGGAGGTACCAGCGCTGGTCCAGGATGCGCAGCTGTAAAGTTGTGAATATATGTATTTGGTCTTTTTCCTTGTTTGCTGGCCTACAACTCTTAAAATCCTTGGAATCTTCAAAGTGATGTGTCTTTTTGTATGCTAATGAGTTGACTAATGGCTGGCAGCCTCTAGGTGGCTTCTGGATAAGAGCTGGTCACCAGGAAGACCAAGGCCAGATTAGAGGGTTGGGACATTCGGTCCTACTCCGCAACCACCATGGAGACAGTCTGAAGGTTAACTTGATCACCAATGGCCAATAATTTCATCAATCATGCCAGTGTAATGAAGCCAGCATAAAAACTCAAAAGGACAGGGCTCAGAGAGTTCCATTAGCTGAACATTGGAGGTTCCCACAAGTGGCATGCCCGGAGGGGGTTATGGAAGCTTCACACCCTTTCCCCATACCTCACCCTGTGCATCTCTTCATCTGTATCTTCTGTAATATCCTTTATAATACGCCATTAAATATAAGGAAGTATTTCTCTGAGTTCTGTGAGCCACTCTACCACATTAATCGAACCCCATGGGGAAGCTGAGTAAAGTTTCAAGTGGAGTAAAATTGCTGATACCGTGACCATCAGGTCAATGTTGCTGGAAGCACAGGTAAAACAACCT

Offspring


GAAAGTTGTGCACAATATAAAAATTATAATTTTATATTTCAAAACAAATTAAATATCTTAAAATTATAGAAGACATTAAAGAACTATATAAATCAAAGTTAGAAAAAAACCCAGATGTGAGTTGGGAAATCTGAAGAAAATTTAAAAGAGAAATTTAAAAATATTAATATAAAAAATGAAGACTAAACTGGAAAGATACACTAGAGTGAATAAACAAAATAGAAAATACTCAGATGTTTTGTTTTAACTTCCTATTGTATGAGTTTTGGAGACCAACATAAGATAATGACTTGCCTCTGGATATGAAGGTAAAAAAACAGACACAGGCCTATGTAGTGATTTCTTACAGAACAACACAGCAGAAAGCAAATCCCTAAAAAACCATGTGGACGTGGCTTTTACAGATGGTTGTCCAATCCCTGCATGCTATTGCTTGCTTATGGATGAGTGAAAGGAATAAAAATTTTAAGTTATAGCTACAGTTTCTCTACCTGTACATTCCAATACTGACCTTGCATGGTTTCTTTGAGGGCTAAGTATGACAAAAGGATGCAGTGATTTCGAACTTAGATTTTAAAAAACAAATATGACTCTTTTGAACTGTGTGAACATAGGCACATTGCTGGATCTGAGTAATTTCATGTGCTAAGAGGGAATAATAGCATCAGCCTTAATGCTGCATTATTGCATTTAGCATTATTTCTTTCTGAAGATGAAAGAAGACAGACATCATTATATTTAACAAAGTGCCTGGCACATATAAAATAGTCAATAAATGTTATCTATCATTGCTATTATTACCTAATACTGCGCATAGTAAGCCCTGAACCTGTTCCTGGCATGTGGAGCTATGTACTATGTTCATGACATTAAACAAAGTAGTAGCTATATAATGAATATATAAATGTGACTTTTATTATTACATCCCTGTAGTTTTGGCAAGTAGTTTACTAAAAGGAAGTTCCAATTTTGACTTAGCATGGAGTTTGTTTTTATCCTGGGCATGTTATCTACCCAGCTTACCTTATTCTTCCTTTCTTCGAAACAGGAATCATGCTTGTTAATTGACTGGGATGTTGCAAGGCCTTATATCTGAGAAGTATATCATCAAGGAATAGAGAAGATGAGGCTTAGAGAGGAAATGGAAGCCCCTGTCAATTAGGAGAGGCAAAGGCTCTATGATACAGCATAGCCTAAGAATTTCGTTGATACAGAATTCTAAGTGTGAAACGAATGAATGGAGTGACCACTCCTCCCTACTAAAGAATCTTGTAAACACTAGTTTTAAAAGCACAAACGTATTATATCATATACCTATGTATAATGTCATTTTGCTACTTTTCTCTTCCAACTTCTCAAATCTTTGAATGCAGGGGTTTTTGGAGTTATTCCCTGTGTATTATTTCGACTGATATGTAATAGCTGCTCAGCGAATGTGTGTTGCTAAATAAGAGATGGAGTACAGACAAGCTGAAATTGCACATTTATGTTGCCATTGTACTGCTCAAAAAAAAAAAAAATTAGAATTAGGGTTAAAGAGAGTGCTCAGGCCCTAGACTAGGATTTATTTGCTGTATAATAAACTTTATGCAAACAATTAACCTCCCTGCTTCTCAATTTTCTCCTCTATAAAATTGGGTTATTACAAAATTCTTTGTAACATATTATGGAGTTCAATTAGGATAAGTTAAATATTGGAAATCTGAAGCATTATGCAAATATGAGGCATTATTATAATAATTATAACAATATTGTTTTTATTCTTAATTGCTACTCTTGAGTACTCTGTTGCTCTGCAGATATCTCTCTCCCTGCCTTCCCCAGGGTGTTGGCATACCAGGATGCCTCTTTAGAAAAGAAATTGCACGATGGACCTAAGGAAACAGAATTTTCCATCCTGGCATTTGCATAAAGGCCACACATGCATAGCCATATGCTGATTTAACCAACAGCTTTCACACTTATAATCGAGTTTGCTACTTGTTCTGCGATATCTACTCTCCCTCTATTTCTTATTAATAGAACAAAATTTTAGTTGGGAATATGGCTACTGAGAATAAAGATTACCTTTCTCAGCTTCTTTGCGGCTAACTCTGATTATGTGTCTAAACTTTGGTGCATATTTTGGTAAACGGAAATTCTTAAAGGGAGATTCTCTACTTTCTTCCTGCTTGCTGGAATGCAAACATGATTGTTGGATTTGAGCAGCCATCTTATGCCAGGAGTTGGAAACCATGCAGGCAGATCCTGGTCATTAGCACTACAGACCTCTATACCAAACTGGATTTCTGTGAGACTCCAGAAGAAAGTAAGCAGCACAAGGAGTTTCTTCATGTATTCTTCATTTCCCACACCCCATTATACGTGCTTTTGCTGTAATCTGGAATCAGTTGTACTAATCTACTGCACATACCTAGATTCTATTGATAGTCTATTCCAGGATTGATAACTTTGAGCCCAGATAACTTGCAGTAAGATTTATAACAAGATTTCAAAAATATTCTTTCCTATACACCAAATAGTTTTGGTTAGAGAAAACAAAACTTTTGGCATAGCAACTTCATTTGTAGGAAGTTACCTTCTTAAAATTGTTTATCTGTGGACAGCTATGCTGCTATTAGTAGGGAATGGTTTCAGGCAAAAGGTTACAGAAGGATGGAGAGGGCCTGGGCTTTGGGGTTCCAGGGGTATGGAAGTCAGCAGAGCTGAGAGTAGTTCCCAACAGCCAGAGTGTCCATGGATCAAGCCCTTTTGTGAAGCTGGAGGTACCAGCGCTGGTCCAGGATGCGCAGCTGTAAAGTTGTGAATATATGTATTTGGTCTTTTTCCTTGTTTGCTGGCCTACAACTCTTAAAATCCTTGGAATCTTCAAAGTGATGTGTCTTTTTGTATGCTAATGAGTTGACTAATGGCTGGCAGCCTCTAGGTGGCTTCTGGATAAGAGCTGGTCACCAGGAAGACCAAGGCCAGATTAGAGGGTTGGGACATTCGGTCCTACTCCGCAACCACCATGGAGACAGTCTGAAGGTTAACTTGATCACCAATGGCCAATAATTTCATCAATCATGCCAGTGTAATGAAGCCAGCATAAAAACTCAAAAGGACAGGGCTCAGAGAGTTCCATTAGCTGAACATTGGAGGTTCCCACAAGTGGCATGCCCGGAGGGGGTTATGGAAGCTTCACACCCTTTCCCCATACCTCACCCTGTGCATCTCTTCATCTGTATCTTCTGTAATATCCTTTATAATACGCCATTAAATATAAGGAAGTATTTCTCTGAGTTCTGTGAGCCACTCTACCACATTAATCGAACCCCATGGGGAAGCTGAGTAAAGTTTCAAGTGGAGTAAAATTGCTGATACCGTGACCATCAGGTCAATGTTGCTGGAAGCACAGGTAAAACAAACT

Overlay - SNPs from both parents are present in the Offspring

GAAAGTTGTGCACAATATAAAAATTATAATTTTATATTTCAAAACAAATTAAATATCTTAAAATTATAGAAGACATTAAAGAACTATATAAATCAAAGTTAGAAAAAAACCCAGATGTGAGTTGGGAAATCTGAAGAAAATTTAAAAGAGAAATTTAAAAATATTAATATAAAAAATGAAGACTAAACTGGAAAGATACACTAGAGTGAATAAACAAAATAGAAAATACTCAGATGTTTTGTTTTAACTTCCTATTGTATGAGTTTTGGAGACCAACATAAGATAATGACTTGCCTCTGGATATGAAAGTAAAAAAACAGACACAGGCCTATGTAGTGATTTCTTACAGAACAACACAGCAGAAAGCAAATCCCTAACAAACCATGTGGACGTGGCTTTTACAGATGGTTGTCCAATCCCTGCATGCTATTGCTTGCTTATGGATGAGTGAAAGGAATAAAAATTTTAAGTTATAGCTACAGTTTCTCTACCTGTACATTCCAATACTGACCTTGCATGGTTTCTTTGAGGGCTAAGTATGACAAAAGGATGCAGTGATTTCGAACTTAGATTTTAAAAAACAAATATGACTCTTTTGAACTGTGTGAACATAGGCACATTGCTGGATCTGAGTAATTTCATGTGCTAAGAGGGAATAATAGCATCAGCCTTAATGCTGCATTATTGCATTTAGCATTATTTCTTTCTGAAGATGAAAGAAGACAGACATCATTATATTTAACAAAGTGCCTGGCACATATAAAATAGTCAATAAATGTTATCTATCATTGCTATTATTACCTAATACTGCGCATAGTAAGCCCTGAACCTGTTCCTGGCATGTGGAGCCATGTACTATGTTCATGACATTAAACAAAGTAGTAGCTATATAATGAATATATAAATGTGACTTTTATTATTACATCCCTGTAGTTTTGGCAAGTAGTTTACTAAAAGGAAGTTCCAATTTTGACTTAGCATGGAGTTTGTTTTTATCCTGGGCATGTTATCTACCCAGCTTACCTTATTCTTCCTTTCTTCGAAACAGGAATCATGCTTGTTAATTGACTGGGATGTTGCAAGGCCTTATATCTGAGAAGTATATCATCAAGGAATAGAGAAGATGAGTCTTAGAGAGGAAATGGAAGCCCCTGTCAATTAGGAGAGGCAAAGGCTCTATGATACAGCATAGCCTAAGAATTTCGTTGATACAGAATTCTAAGTGTGAAACGAATGAATGGAGTGACCACTCCTCCCTACTAAAGAATCTTGTAAACACTAGTTTTAAAAGCACAAACGTATTATATCATATACCTATGTATAATGTCATTTTGCTACTTTTCTCTTCCAACTTCTCAAATCTTTGAATGCAGGGGTTTTTGGAGTTATTCCCTGTGTATTATTTCGACTGATATGTAATAGCTGCTCAGCGAATGTGTGTTGCTAAATAAGAGATGGAGTACAGACAAGCTGAAATTGCACATTTATGTTGCCATTGTACTGCTCAAAAAAAAAAAAAATTAGAATTAGGGTTAAAGAGAGTGCTCAGGCCCTAGACTAGGATTTATTTGCTGTATAATAAACTTTATGCAAACAATTAACCTCCCTGCTTCTCAATTTTCTCCTCTATAAAATTGGGTTATTACAAAATTCTTTGTAACATATTATGGAGTTCAATTAGGATAAGTTAAATATTGGAAATCTGAAGCATTATGCAAATATGAGGCATTATTATAATAATTATAACAATATTGTTTTTATTCTTAATTGCTACTCTTGAGTACTCTGTTGCTCTGCAGATATCTCTCTCCCTGCCTTCCCCAGGGTGTTGGCATACCAGGATGCCTCTTTAGAAAAGAAATTGTACGATCGACCTAAGGAAACAGAATTTTCCATCCTGGCATTTGCATAAAGGCCACACATGCATAGCCATATGCTGATTTAACCAACAGCTTTCACACTTATAATCGAGTTTGCTACTTGTTCTGCGATATCTACTCTCCCTCTATTTCTTATTAATAGAACAAAATTTTAGTTGGGAATATGGCTACTGAGAATAAAGATTACCTTTCTCAGCTTCTTTGCGGCTAACTCTGATTATGTGTCTAAACTTTGGTGCATATTTTGGTAAACGGAAATTCTTAAAGGGAGATTCTCTACTTTCTTCCTGCTTGCTGGAATGCAAACATGATTGTTGGATTTGAGCAGCCATCTTATGCCAGGAGTTGGAAACCATGCAGGCAGATCCTGGTCATTAGCACTACAGACCTCTATACCAAACTGGATTTCTGTGAGACTCCAGAAGAAAGTAAGCAGCACAAGGAGTTTCTTCATGTATTCTTCATTTCCCACACCCCATTATACGTGCTTTTGCTGTAATCTGGAATCAGTTGTACTAATCTACTGCACATACCTAGATTCTATTGATAGTCTATTCCAGGATTGATAACTTTGAGCCCAGATAACTTGCAGTAAGATTTATAACAAGATTTCAAAAATATTCTTTCCTATACACCAAATAGTTTTGGTTAGAGAAAACAAAACTTTTGGCATAGCAACTTCATTTGTAGGAAGTTACCTTCTTAAAATTGTTTATCTGTGGACAGCTATGCTGCTATTAGTAGGGAATGGTTTCAGGCAAGAGGTTACAGAAGGATGGAGAGGGCCTGGGCTTTGGGGTTCCAGGGGTATGGAAGTCAGCAGAGCTGAGAGTAGTTCCCAACAGCCAGAGTGTCCATGGATCAAGCCCTTTTGTGAAGCTGGAGGTACCAGCGCTGGTCCAGGATGCGCAGCTGTAAAGTTGTGAATATATGTATTTGGTCTTTTTCCTTGTTTGCTGGCCTACAACTCTTAAAATCCTTGGAATCTTCAAAGTGATGTGTCTTTTTGTATGCTAATGAGTTGACTAATGGCTGGCAGCCTCTAGGTGGCTTCTGGATAAGAGCTGGTCACCAGGAAGACCAAGGCCAGATTAGAGGGTTGGGACATTCGGTCCTACTCCGCAACCACCATGGAGACAGTCTGAAGGTTAACTTGATCACCAATGGCCAATAATTTCATCAATCATGCCAGTGTAATGAAGCCAGCATAAAAACTCAAAAGGACAGGGCTCAGAGAGTTCCATTAGCTGAACATTGGAGGTTCCCACAAGTGGCATGCCCGGAGGGGGTTATGGAAGCTTCACACCCTTTCCCCATACCTCACCCTGTGCATCTCTTCATCTGTATCTTCTGTAATATCCTTTATAATACGCCATTAAATATAAGGAAGTATTTCTCTGAGTTCTGTGAGCCACTCTACCACATTAATCGAACCCCATGGGGAAGCTGAGTAAAGTTTCAAGTGGAGTAAAATTGCTGATACCGTGACCATCAGGTCAATGTTGCTGGAAGCACAGGTAAAACAACCT

GAAAGTTGTGCACAATATAAAAATTATAATTTTATATTTCAAAACAAATTAAATATCTTAAAATTATAGAAGACATTAAAGAACTATATAAATCAAAGTTAGAAAAAAACCCAGATGTGAGTTGGGAAATCTGAAGAAAATTTAAAAGAGAAATTTAAAAATATTAATATAAAAAATGAAGACTAAACTGGAAAGATACACTAGAGTGAATAAACAAAATAGAAAATACTCAGATGTTTTGTTTTAACTTCCTATTGTATGAGTTTTGGAGACCAACATAAGATAATGACTTGCCTCTGGATATGAAGGTAAAAAAACAGACACAGGCCTATGTAGTGATTTCTTACAGAACAACACAGCAGAAAGCAAATCCCTAAAAAACCATGTGGACGTGGCTTTTACAGATGGTTGTCCAATCCCTGCATGCTATTGCTTGCTTATGGATGAGTGAAAGGAATAAAAATTTTAAGTTATAGCTACAGTTTCTCTACCTGTACATTCCAATACTGACCTTGCATGGTTTCTTTGAGGGCTAAGTATGACAAAAGGATGCAGTGATTTCGAACTTAGATTTTAAAAAACAAATATGACTCTTTTGAACTGTGTGAACATAGGCACATTGCTGGATCTGAGTAATTTCATGTGCTAAGAGGGAATAATAGCATCAGCCTTAATGCTGCATTATTGCATTTAGCATTATTTCTTTCTGAAGATGAAAGAAGACAGACATCATTATATTTAACAAAGTGCCTGGCACATATAAAATAGTCAATAAATGTTATCTATCATTGCTATTATTACCTAATACTGCGCATAGTAAGCCCTGAACCTGTTCCTGGCATGTGGAGCTATGTACTATGTTCATGACATTAAACAAAGTAGTAGCTATATAATGAATATATAAATGTGACTTTTATTATTACATCCCTGTAGTTTTGGCAAGTAGTTTACTAAAAGGAAGTTCCAATTTTGACTTAGCATGGAGTTTGTTTTTATCCTGGGCATGTTATCTACCCAGCTTACCTTATTCTTCCTTTCTTCGAAACAGGAATCATGCTTGTTAATTGACTGGGATGTTGCAAGGCCTTATATCTGAGAAGTATATCATCAAGGAATAGAGAAGATGAGTCTTAGAGAGGAAATGGAAGCCCCTGTCAATTAGGAGAGGCAAAGGCTCTATGATACAGCATAGCCTAAGAATTTCGTTGATACAGAATTCTAAGTGTGAAACGAATGAATGGAGTGACCACTCCTCCCTACTAAAGAATCTTGTAAACACTAGTTTTAAAAGCACAAACGTATTATATCATATACCTATGTATAATGTCATTTTGCTACTTTTCTCTTCCAACTTCTCAAATCTTTGAATGCAGGGGTTTTTGGAGTTATTCCCTGTGTATTATTTCGACTGATATGTAATAGCTGCTCAGCGAATGTGTGTTGCTAAATAAGAGATGGAGTACAGACAAGCTGAAATTGCACATTTATGTTGCCATTGTACTGCTCAAAAAAAAAAAAAATTAGAATTAGGGTTAAAGAGAGTGCTCAGGCCCTAGACTAGGATTTATTTGCTGTATAATAAACTTTATGCAAACAATTAACCTCCCTGCTTCTCAATTTTCTCCTCTATAAAATTGGGTTATTACAAAATTCTTTGTAACATATTATGGAGTTCAATTAGGATAAGTTAAATATTGGAAATCTGAAGCATTATGCAAATATGAGGCATTATTATAATAATTATAACAATATTGTTTTTATTCTTAATTGCTACTCTTGAGTACTCTGTTGCTCTGCAGATATCTCTCTCCCTGCCTTCCCCAGGGTGTTGGCATACCAGGATGCCTCTTTAGAAAAGAAATTGCACGATGGACCTAAGGAAACAGAATTTTCCATCCTGGCATTTGCATAAAGGCCACACATGCATAGCCATATGCTGATTTAACCAACAGCTTTCACACTTATAATCGAGTTTGCTACTTGTTCTGCGATATCTACTCTCCCTCTATTTCTTATTAATAGAACAAAATTTTAGTTGGGAATATGGCTACTGAGAATAAAGATTACCTTTCTCAGCTTCTTTGCGGCTAACTCTGATTATGTGTCTAAACTTTGGTGCATATTTTGGTAAACGGAAATTCTTAAAGGGAGATTCTCTACTTTCTTCCTGCTTGCTGGAATGCAAACATGATTGTTGGATTTGAGCAGCCATCTTATGCCAGGAGTTGGAAACCATGCAGGCAGATCCTGGTCATTAGCACTACAGACCTCTATACCAAACTGGATTTCTGTGAGACTCCAGAAGAAAGTAAGCAGCACAAGGAGTTTCTTCATGTATTCTTCATTTCCCACACCCCATTATACGTGCTTTTGCTGTAATCTGGAATCAGTTGTACTAATCTACTGCACATACCTAGATTCTATTGATAGTCTATTCCAGGATTGATAACTTTGAGCCCAGATAACTTGCAGTAAGATTTATAACAAGATTTCAAAAATATTCTTTCCTATACACCAAATAGTTTTGGTTAGAGAAAACAAAACTTTTGGCATAGCAACTTCATTTGTAGGAAGTTACCTTCTTAAAATTGTTTATCTGTGGACAGCTATGCTGCTATTAGTAGGGAATGGTTTCAGGCAAAAGGTTACAGAAGGATGGAGAGGGCCTGGGCTTTGGGGTTCCAGGGGTATGGAAGTCAGCAGAGCTGAGAGTAGTTCCCAACAGCCAGAGTGTCCATGGATCAAGCCCTTTTGTGAAGCTGGAGGTACCAGCGCTGGTCCAGGATGCGCAGCTGTAAAGTTGTGAATATATGTATTTGGTCTTTTTCCTTGTTTGCTGGCCTACAACTCTTAAAATCCTTGGAATCTTCAAAGTGATGTGTCTTTTTGTATGCTAATGAGTTGACTAATGGCTGGCAGCCTCTAGGTGGCTTCTGGATAAGAGCTGGTCACCAGGAAGACCAAGGCCAGATTAGAGGGTTGGGACATTCGGTCCTACTCCGCAACCACCATGGAGACAGTCTGAAGGTTAACTTGATCACCAATGGCCAATAATTTCATCAATCATGCCAGTGTAATGAAGCCAGCATAAAAACTCAAAAGGACAGGGCTCAGAGAGTTCCATTAGCTGAACATTGGAGGTTCCCACAAGTGGCATGCCCGGAGGGGGTTATGGAAGCTTCACACCCTTTCCCCATACCTCACCCTGTGCATCTCTTCATCTGTATCTTCTGTAATATCCTTTATAATACGCCATTAAATATAAGGAAGTATTTCTCTGAGTTCTGTGAGCCACTCTACCACATTAATCGAACCCCATGGGGAAGCTGAGTAAAGTTTCAAGTGGAGTAAAATTGCTGATACCGTGACCATCAGGTCAATGTTGCTGGAAGCACAGGTAAAACAACCT

A

What is GraphBWT?

Core Technology to Make Anchored Assembly Feasible

• Needed a way to represent the read data that was graph based

• Fast search for variation from reference directly from the reads in a whole genome dataset

• Small enough footprint to store a read overlap graph of whole human genome in memory

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GraphBWT

• Technology for storing all of the reads that comprise the variation graph of a whole human genome

• Very compact to fit into memory (1.5 bytes per base)

• In memory, allows for extremely fast searches via subsequence

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Resulting technologies that use GraphBWT

SpEC SV and Query

• SpEC: A lossless compression format that reduces BAM files to 50% of their original size and that can be analyzed with existing bioinformatics tools while compressed

• SpEC SV: SpEC that also includes a compact sequence index, known as a GraphBWT (3GB), which is a graph based representation of genomic variation

• SpEC Query: an API that reads SpEC SV files to enable rapid queries of sequence data via location or by a subsequence

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Create a SpEC SV File

Spiral’s SpEC SV File

Query Times

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Samples, Variant calls SpEC Query using SpEC SpEC Query using SpEC SV

1 sample, 1 variant Milliseconds Milliseconds

1 sample, 1M variants 10 Minutes 5 Minutes

1000 samples, 1 variant 10-‐20 Minutes 10-‐20 Minutes

1000 samples, 1M variants 4 Days 2 Days

Variant types SNPs and Indels SNPs, Indels and SVs

GraphBWT Technical Details

• Constant time traversal of k-mer graph for any sized k-mer

• Subsequence search linear with size of sequence

• Storage requirements grow linearly with size of novel sequence (i.e. variation)

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Use Cases for SpEC SV

• Search for evidence of variation in read data

• Compare graphs between individuals for unique variation

• Compare combined graphs of two groups

• Store variation, for example a reference genome

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Questions?

Niranjan Shekar - VP of Bioinformatics [email protected]

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Aug2015 analysis team spiral genetics

Health & Medicine

Transcript of Aug2015 analysis team spiral genetics