{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T12:03:40Z","timestamp":1777464220227,"version":"3.51.4"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Differential detection on symptom-related pathogens (SRP) is critical for fast identification and accurate control against epidemic diseases. Conventional polymerase chain reaction (PCR) requires a large number of unique primers to amplify selected SRP target sequences. With multiple-use primers (mu-primers), multiple targets can be amplified and detected in one PCR experiment under standard reaction condition and reduced detection complexity. However, the time complexity of designing mu-primers with the best heuristic method available is too vast. We have formulated minimum-set mu-primer design problem as a set covering problem (SCP), and used modified compact genetic algorithm (MCGA) to solve this problem optimally and efficiently. We have also proposed new strategies of primer\/probe design algorithm (PDA) on combining both minimum-set (MS) mu-primers and unique (UniQ) probes. Designed primer\/probe set by PDA-MS\/UniQ can amplify multiple genes simultaneously upon physical presence with minimum-set mu-primer amplification (MMA) before intended differential detection with probes-array hybridization (PAH) on the selected target set of SRP.<\/jats:p>\n               <jats:p>Results: The proposed PDA-MS\/UniQ method pursues a much smaller number of primers set compared with conventional PCR. In the simulation experiment for amplifying 12\u2009669 target sequences, the performance of our method with 68% reduction on required mu-primers number seems to be superior to the compared heuristic approaches in both computation efficiency and reduction percentage. Our integrated PDA-MS\/UniQ method is applied to the differential detection on 9 plant viruses from 4 genera with MMA and PAH of 11 mu-primers instead of 18 unique ones in conventional PCR while amplifying overall 9 target sequences. The results of wet lab experiments with integrated MMA-PAH system have successfully validated the specificity and sensitivity of the primers\/probes designed with our integrated PDA-MS\/UniQ method.<\/jats:p>\n               <jats:p>Contact: \u00a0cykao@csie.ntu.edu.tw<\/jats:p>\n               <jats:p>Supplementary information: \u00a0<\/jats:p>","DOI":"10.1093\/bioinformatics\/bti730","type":"journal-article","created":{"date-parts":[[2005,10,27]],"date-time":"2005-10-27T00:12:37Z","timestamp":1130371957000},"page":"4330-4337","source":"Crossref","is-referenced-by-count":20,"title":["Integrated minimum-set primers and unique probe design algorithms for differential detection on symptom-related pathogens"],"prefix":"10.1093","volume":"21","author":[{"given":"Yu-Cheng","family":"Huang","sequence":"first","affiliation":[{"name":"Bioinformatics Laboratory, Department of Computer Science and Information Engineering, National Taiwan University 1 \u00a0 1 \u00a0 \u00a0 Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Fan","family":"Chang","sequence":"additional","affiliation":[{"name":"Breed-Use-Special Laboratory, Center of Agriculture Hierarchical Utilization, Graduate Institute of Biotechnology, Chinese Culture University 3 \u00a0 3 \u00a0 \u00a0 Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-hsiung","family":"Chan","sequence":"additional","affiliation":[{"name":"Bioinformatics Laboratory, Department of Computer Science and Information Engineering, National Taiwan University 1 \u00a0 1 \u00a0 \u00a0 Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tze-Jung","family":"Yeh","sequence":"additional","affiliation":[{"name":"Bioinformatics Laboratory, Department of Computer Science and Information Engineering, National Taiwan University 1 \u00a0 1 \u00a0 \u00a0 Taipei, Taiwan"},{"name":"Department of Plant Pathology and Microbiology, National Taiwan University 2 \u00a0 2 \u00a0 \u00a0 Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Chun","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Plant Pathology and Microbiology, National Taiwan University 2 \u00a0 2 \u00a0 \u00a0 Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaur-Chin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Computer Science, National Tsing-Hua University 4 \u00a0 4 \u00a0 \u00a0 Hsinchu, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Yan","family":"Kao","sequence":"additional","affiliation":[{"name":"Bioinformatics Laboratory, Department of Computer Science and Information Engineering, National Taiwan University 1 \u00a0 1 \u00a0 \u00a0 Taipei, Taiwan"},{"name":"Institute for Information Industry 5 \u00a0 5 \u00a0 \u00a0 Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,10,25]]},"reference":[{"key":"2023061007215446000_b1","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1057\/palgrave.jors.2601317","article-title":"An indirect genetic algorithm for set covering problem","volume":"50","author":"Aickelin","year":"2002","journal-title":"J. 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