Minimum Set Primers and Unique Probes Design Algorithms for
Differential Detection of Symptom-Related Pathogens
Wet Lab Experimental Results - Sensitivity & Specificity (Supplementary Material) (pdf)
Wet Lab Experimental Results (Supplementary Material) (pdf)
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The differential detection of symptom-related pathogens is critical for the fast identification and correct treatment of epidemic diseases. Conventional PCR requires a large number of primers for amplification of candidate sequences . This is costly and results in a high false-negative rate. The use of multiple-use primers can largely reduce the cost of diagnostic PCR. However, the time complexity of the best heuristic method available is too large. We have formulated the primer design problem as a minimum set covering problem (SCP), and used modified compact genetic algorithm (MCGA) to solve this problem. We also proposed new strategies combining both unique (UniQ) probes and minimum set (MS) primers . They amplify multiple genes simultaneously for differential detection of a set of pathogens causing similar symptoms. The proposed method uses a much smaller number of primers. In our trial experiment, for amplification of 12,669 target sequences, the number of primers required is reduced by 68%. The performance of our method is better than other heuristic approaches in terms of efficiency and percent of reduction. The method has been applied to the identification of 9 plant viruses from 4 genus. Conventional PCR requires 18 primers to amplify 9 target sequences . O ur integrated UniQ/MS method requires only 11 multiple-use primers. Our results have been validated with wet lab experiments. |
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Last Update: 2005.08.01