Aug2015 analysis team 01 a jtrio_denovo_assembly_variants_chunlin_08272015

1. Assembly based variant discovery for AJtrio using
cortex: a preliminary analysis
Chunlin Xiao

2. De novo assembly and genotyping of variants using colored de Bruijn graphs
Zamin Iqbal, Mario Caccamo, Isaac Turner, Paul Flicek & Gil McVean
Nature Genetics 44, 226–232 (Jan 2012)
• First assembly-based multiple samples variant caller (cortex)
• Looking for all types of variants (SNPs, indels, inversions, complex variants, small haplotypes) at the same time
• Errors/Repeats/Variants can introduce BUBBLES in multi-sample graph
• Find all BUBBLES from multi-sample graph, then classify them under three models (error, repeat, or variant) after building/cleaning
the multi-sample graph
Bubble coverage varies with genotypes - A SNP can form a bubble of length k
(example k=4)
Zamin Iqbal
Two sides of the bubble presented in ALL samples

3. Datasets used
• GIAB AJtrio Illumina HiSeq 300X as input
• ftp://ftp-trace.ncbi.nlm.nih.gov/giab/ftp/data/AshkenazimTrio/HG002_NA24385_son/NIST_HiSeq_HG002_Homogeneity-
10953946/HG002_HiSeq300x_fastq/
• ftp://ftp-
trace.ncbi.nlm.nih.gov/giab/ftp/data/AshkenazimTrio/HG003_NA24149_father/NIST_HiSeq_HG003_Homogeneity-
12389378/HG003_HiSeq300x_fastq/
• ftp://ftp-
trace.ncbi.nlm.nih.gov/giab/ftp/data/AshkenazimTrio/HG004_NA24143_mother/NIST_HiSeq_HG004_Homogeneity-
14572558/HG004_HiSeq300x_fastq/

4. Summary of AJtrio variant raw calls with cortex (GRCh37)
Variant Types GRCh37
# PASS
(total)
3,177,560
(out of 3,363,520)
SNP 2,695,604
PH_SNPS* 125,165
DEL 168,069
INS 153,300
INV_INDEL* 102
COMPLEX* 35,320
*PH_SNPS="Phased SNPs“ (small haplotypes)
*INV_INDEL="Inversion+indel”
*COMPLEX="Complex variant, collection of SNPs and indels”
*reference binary was loaded in multi-sample graph. Chromosomes only.
Son Parent1 Parent2
# Mendelian
inconsistencies
0/0 1/1 */* 17959
1/1 0/0 */* 19574
0/1 0/0 0/0 1120
0/1 1/1 1/1 89
38,742
Longest in size PH_SNP 419bps
0
20000
40000
60000
80000
100000
120000
1001
~
1500
201
~
500
51 ~
100
11 ~
25
9 7 5 3 1 1 3 5 7 9 11 ~
25
51 ~
100
201
~
500
1001
~
1500
2001
+
Counts
Size (bps)
AJ Trio INS/DEL size distributions (GRCh37)
DEL
Longest in size: DEL 1980bps; INS 2035bps; >=50bps: 727
Longest in size 2700bps ; >=50bps: 1,101

5. • Zamin Iqbal
• Justin Zook
• Jon Trow and SRA group
• Steve Sherry
Acknowledgements