ChannelIndependent Viterbi Algorithm CIVA for DNA Sequencing

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Channel-Independent Viterbi Algorithm (CIVA) for
DNA Sequencing

• Xiaohua (Edward) Li
• Department of Electrical and Computer Engineering
• State University of New York at Binghamton

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Outline

• Introduction
• CIVA
• Use CIVA for base-calling
• Simulations
• Conclusions

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Introduction DNA sequencing

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

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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

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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

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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)

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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

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CIVA for Base-calling

• Model trace signal with communication system
• Channel effect introduces ISI

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Symbol Matrix Structure
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Probe Construction
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Probe Construction Example
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Trellis Metric Calculation
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CIVA Trellis Search
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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

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Simulations Experiment 1

• A trace file with reference bases from Staden
  Package
• Normalize trace, find approximate base interval,
  apply CIVA with MP1 (2-tap channel. 25 trellis
  states, 125 transitional paths)
• Results less than 3 error compared with
  reference

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Simulations Experiment 1

• Two zoom-in sections
• 1. with confident base detections
• 2. with undetermined N

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Simulations Experiment 2

• A gel image from Prof. S. Gal with low quality
• Scanning to trace signal

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Simulations Experiment 2

• Apply CIVA for base-calling
• A zoom-in section

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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