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Channel-Independent Viterbi Algorithm (CIVA) for DNA Sequencing

Channel-Independent Viterbi Algorithm (CIVA) for DNA Sequencing. Xiaohua (Edward) Li Department of Electrical and Computer Engineering State University of New York at Binghamton. Outline. Introduction CIVA Use CIVA for base-calling Simulations Conclusions. Introduction: DNA sequencing.

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Channel-Independent Viterbi Algorithm (CIVA) for DNA Sequencing

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  1. Channel-Independent Viterbi Algorithm (CIVA) for DNA Sequencing Xiaohua (Edward) Li Department of Electrical and Computer Engineering State University of New York at Binghamton

  2. Outline • Introduction • CIVA • Use CIVA for base-calling • Simulations • Conclusions

  3. Introduction: DNA sequencing • DNA sequencing (base-calling) • Procedure • template, PCR, electrophoresis, gel image, trace file • Base-caller

  4. Introduction: Base-caller • Base-calling: detect DNA base sequence • Approaches • Manual reading, automated by heuristic knowledge • Image processing with signal models (ABI, Phred) • Deconvolution with communication (ISI) signal model, e.g., MLSE, MAP

  5. Proposed Method: CIVA • Our method: with ISI model, robust to signal irregularity • Difficulty comes from irregular trace signal • Amplitude and position jitter • Short signal, limited samples, yet time-varying • Solution: CIVA • joint symbol/position optimization • without channel estimation

  6. CIVA: Basic Idea • List all possible symbol matrices S(n), • Find a probe for each possible S(n) • Use all probes to determine S(n) from X(n)

  7. CIVA: Properties • CIVA: a trellis searching algorithm where metrics are calculated by probes • Properties • Near optimal for even ill-conditioned channels • No channel estimation, channel independent • High computational complexity • Applications • Direct application: system with simple signaling and short channel, e.g., GSM, sensor networks, base-calling • Future: more application with complexity reduction

  8. CIVA for Base-calling • Model trace signal with communication system • Channel effect introduces ISI

  9. Symbol Matrix Structure

  10. Probe Construction

  11. Probe Construction Example

  12. Trellis Metric Calculation

  13. CIVA Trellis Search

  14. Special Consideration for DNA Trace Signal • Amplitude jitter • solved inherently • Limited trace samples and time varying • fast convergence of CIVA • Timing jitter • looking for best timing for each sample

  15. Simulations: Experiment 1 • A trace file with reference bases from Staden Package • Normalize trace, find approximate base interval, apply CIVA with M=P=1 (2-tap channel. 25 trellis states, 125 transitional paths) • Results: less than 3% error compared with reference

  16. Simulations: Experiment 1 • Two zoom-in sections • #1. with confident base detections • #2. with undetermined N

  17. Simulations: Experiment 2 • A gel image from Prof. S. Gal with low quality • Scanning to trace signal

  18. Simulations: Experiment 2 • Apply CIVA for base-calling • A zoom-in section

  19. Conclusions • CIVA algorithm proposed for DNA sequence base-calling • Robust to signal irregularity with affordable computational complexity • Experiments show positive performance • More experiments are required for evaluation

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