1000 Genomes SV detection Boston College

1. 1000 Genomes SV detectionBoston College Chip Stewart 24 November 2008

2. Spanner: RP approach Paired-end SV breakpoint detection • Detect clusters of fragments spanning breakpoints • Classify clusters into SV types • Estimate CN from read counts in candidate region Pattern: PE RD DNA REFERENCE LF LM LM ~ LF + Ldel low coverage deletion Ldel tandemduplication LM~ LF – Ldup high coverage Ldup LM LM~ +LinvLM ~ -Linv normal coverage ends flipped inversion Linv Spanner / BC

3. Spanner … RD approach Read Depth Copy Number Variation (CNV) detection • Count uniquely aligned reads in windows (1kb) across chromosomes. • Correct for micro-repeat artifact with an “alignabilty” metric to estimate expected number of uniquely aligned reads in each window. Local copy number is based on the likelihood that the estimated count of reads scaled by copy number will fluctuate (Poisson) to the observed count. • Identify CN breakpoints (this is still in the works) Alignability: Define “alignabilty” for a given chromosome position as: This becomes tractable when considering a random sample of possible reads within a window of positions. Spanner / BC

4. Alignabilty Coverage profiles from NA12878 for a 1.2MB region of chromosome 4. Reads/1kb The count of unique aligned read (up to 4 mismatches) in non-overlapping windows of 1kb. compared with the expected count of reads based on A(p). expected Reads/1kb Chromosome 4 position [Mb] Reads/1kb A(p) has a 90% correlation with observed read coverage variance. Position [Mb] expected Reads/1kb Spanner / BC

5. SV event display matlab tool 300bp ALU deletion in chromosome 1 of NA12878 chromosome overview fragment lengths readdepth eventtrack Spanner / BC

6. Tandem duplication event • NA12878 chromosome 1 Spanner / BC

7. “Complex” SV • NA12878 chromosome 8 Spanner / BC

8. TrioCNV events detected Spanner / BC