1. Gao Song 2010/02/03

2.  Background Knowledge  Problem Description  Framework of Solution  Own Methods  Results

3.  Pair End Tag (PET)

4.  Concordant PET (CPET)  Discordant PET (DPET) ◦ Distance or orientation is incorrect ◦ Map to different chromosomes  DPET Cluster

5.  Given: ◦ Frequency of DPET and CPET along the reference genome ◦ DPET Cluster  Requirement: ◦ Find rearrangement of cancer genome compare to normal human genome ◦ Now focus on Amplicons

6.  The reference genome is cut when CPET is 0 => some big contigs  According to DPET, find the breakpoints  Using CPET to check if there is connection between breakpoints  Convert DPET Cluster into edges in the graph  Using high copy edges to form subgraph of amplicons

7. DPET Start and End Breakpoint CPET Filted BreakPoints Original Contigs Small Contigs DPET Reference Genome Edges CPET Nodes Graph

8.  DPET Frequency Curve  Using DPET directly choose a threshold to Select the breakpoint  Problem: ◦ How to choose the threshold ◦ Within amplicon region, it is hard to find the breakpoint – basic frequency is too much Chromosome 9

9.  Using slope (differentiation)  Problem: ◦ How to define threshold ◦ Too many false positive ◦ Also miss some DPET cluster Chromosome 9

10.  In breakpoint, DPET increases, CPET decreases  Can be used as another criteria  Problem ◦ Another Parameter!

11.  Using slope to find the threshold  The previous missing point can be found

12.  Localize checking  Using two consecutive windows ◦ Each window has: μ σ ◦ Null Hypothesis: σ 2 is not significantly larger than σ 1 ◦ Using Binomial Testing: Significance level: 0.05 window1window2

13.  Some details: ◦ Check if the cluster region is included in window  Not finished yet  Calculating σ is time-consuming - have to recalculate after each step

14. 10k20k # of subgraph7235 Max chromosome in One subgraph 44 Average chromosome In one subgraph 1.181.23 Max edge in One subgraph 4244 Average edge In one subgraph 5.475.77

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