本研究論文主要為開發引子設計(primer design)方法及發展使用者需要的單一核苷酸多型性(single nucleotide polymorphism, SNP)系統以輔助生物學者及研究人員進行關聯性研究。於引子設計問題上，遺傳演算法(Genetic Algorithm, GA)、瀰集演算法(Memetic Algorithm, MA)及粒子族群最佳化(Particle Swarm Optimization, PSO)被應用至專一聚合酶鏈鎖反應(Polymerase Chain Reaction, PCR)引子設計以挑選適當的引子集。此外，以模糊調適慣性權重的粒子族群最佳化(Fuzzy Adaptive inertia weight of PSO, FAPSO)及以混沌慣性權重的粒子族群最佳化(Chaotic Inertia Weight of PSO, CIWPSO)的方法也促進了專一聚合酶鏈鎖反應引子設計。對於聚合酶鏈鎖反應-酵素片段長度多型性(Restriction Fragment Length Polymorphism, RFLP)之引子設計，本研究論文使用遺傳演算法並整合SNP-RFLPing程式的更新核心設計自然及誘導突變的PCR-RFLP引子，為SNP定型上(SNP genotyping)提供適當的引子集及限制酶。特別地，本研究論文引進了遺傳演算法及瀰集演算法設計出時間減少及成本低廉的聚合酶鏈鎖反應-對抗的兩對引子(Confronting Two-Pair Primers, CTPP)。於發展使用者需要的單一核苷酸多型性系統方面，SNP-RFLPing 2提供很多有關於SNP定型所需之PCR-RFLP資訊，如RFLP酵素及引子集。SNP-Flankplus提供16個物種可用的樣版序列以輔助PCR試驗上適當引子集的設計。Prim-SNPing提供自然的引子設計、誘導突變的引子設計、對抗的兩對引子設計及一般的引子設計。由BLAST及品質控制增強設計的引子於PCR上之效率，避免了二級結構影響。Methyl-Typing為改良的COBRA (Combined Bisulfite Restriction Analysis)軟體，提供了限制酶探勘及甲基化胞嘧啶包含序列(methyl-cytosine-containing)於重亞硫酸鹽改變(bisulfite-conversion)之視覺化。Drug-SNPing連結及整合藥物與SNPs相關的資源及工具以輔助藥物基因體學的個人化醫學研究。

The dissertation focuses on the works of developing primer design methods and single nucleotide polymorphism (SNP) user-friendly systems to assist biologists and researchers performing association studies. In the primer design, genetic algorithm (GA), memetic algorithm (MA) and particle swarm optimization (PSO) are applied to specific polymerase chain reaction (PCR) primer design for selection of feasible primer pairs. Furthermore, fuzzy adaptive inertia weight of PSO (FAPSO) and chaotic inertia weight of PSO (CIWPSO) also facilitate the specific PCR primer design. For PCR-restriction fragment length polymorphism (RFLP) primer design, the dissertation uses the GA and integrated the updated core of SNP-RFLPing to design natural and mutagenic PCR-RFLP primers to provide feasible primers and restriction enzymes for SNP genotyping. Specially, this dissertation introduces the GA-based and MA-based methods to design time- and cost-effective PCR-CTPP (Confronting Two-Pair Primers) primers. In the SNP user-friendly systems, SNP-RFLPing 2 is developed to provide PCR-RFLP information such as the RFLP enzymes and their primer set for SNP genotyping in many comprehensive fields related to the SNP. SNP-Flankplus provides an available template sequence to assist the design of feasible primer sets in a PCR assay for SNP genotyping with sixteen organisms. Prim-SNPing provides natural-primer design (PD), mutagenic-PD, and CTPP-PD as well as general-PD. The PCR efficiency for the designed primers is enhanced by BLAST and quality control, thus avoiding secondary structures. Methyl-Typing, an improved COBRA (combined bisulfite restriction analysis) software providing restriction enzyme mining and visualization of methyl-cytosine-containing sequences after bisulfite-conversion. Drug-SNPing connects and integrates between drug- and SNPs-related resources and tools to assist personalized medicine studies of pharmacogenomics.

ABSTRACT IN CHINESE i
ABSTRACT iii
ACKNOWLEDGEMENT v
LIST OF TABLES i
LIST OF FIGURES vi
I. INTRODUCTION 1
1.1 Motive of study 1
1.2 Purpose of study 1
1.3 Organization of the dissertation 3
II. BACKGROUND 5
2.1 Polymerase Chain Reaction (PCR) and primer design 5
2.1.1 Polymerase Chain Reaction (PCR) 5
2.1.2 Primer design 8
2.2 Single Nucleotide Polymorphism (SNP), Restriction Fragment Length Polymorphism (RFLP) and Methylation 11
2.2.1 Single Nucleotide Polymorphism (SNP) 11
2.2.2 Restriction Fragment Length Polymorphism (RFLP) 12
2.2.3 Methylation 13
2.3 Biological databases and bioinformatics tools 15
2.3.1 Biological databases 15
2.3.2 Bioinformatics tools 18
2.4 Algorithms 20
2.4.1 Genetic Algorithm (GA) 20
2.4.2 Memetic Algorithm (MA) 20
2.4.3 Particle Swarm Optimization (PSO) 21
2.4.4 Fuzzy adaptive inertia weight of PSO (FAPSO) 22
2.4.5 Chaotic inertia weight of PSO (CIWPSO) 22
III. PRIMER DESIGN 24
3.1 Specific PCR primer design 24
3.1.1 Problem definition 24
3.1.2 Fitness evaluation 26
3.1.3 GA for specific PCR primer design 30
3.1.4 MA for specific PCR primer design 36
3.1.5 PSO for specific PCR primer design 44
3.1.6 FAPSO for specific PCR primer design 46
3.1.7 CIWPSO for specific PCR primer design 52
3.2 PCR-RFLP primer design 59
3.2.1 Problem definition 59
3.2.1.1 Definition of natural PCR-RFLP primer design 59
3.2.1.2 Definition of mutagenic PCR-RFLP primer design 61
3.2.2 GA for natural PCR-RFLP primer design 64
3.2.3 GA for mutagenic PCR-RFLP primer design 71
3.3 PCR-Confronting Two-Pair Primer (CTPP) design 79
3.3.1 Problem definition 79
3.3.2 Fitness evaluation 82
3.3.3 GA for PCR-CTPP primer design 88
3.3.4 MA for PCR-CTPP primer design 93
IV. SNP RELATED APPLICATIONS AND IMPLEMENTATIONS 99
4.1 SNP-RFLPing 2 99
4.1.1 System structure and functions 99
4.1.2 Database description 103
4.2 SNP-Flankplus 104
4.2.1 System overview 104
4.3 Prim-SNPing 107
4.3.1 System structure and functions 107
4.4 Methyl-Typing 110
4.4.1 System structure and functions 110
4.5 Drug-SNPing 115
4.5.1 System structure and functions 115
V. RESULTS AND DISCUSSION 119
5.1 Specific PCR primer design 119
5.1.1 Datasets and environment 119
5.1.2 Parameter settings for specific PCR primer design 119
5.1.3 Results comparison among the primer design methods 120
5.1.4 Summary of GA, MA and PSO primer design 130
5.1.5 SPD tool and wet-laboratory validation for specific primer design 132
5.2 PCR-RFLP primer design 137
5.2.1 Datasets and environment 137
5.2.2 Parameter settings for PCR-RFLP primer design 137
5.2.3 In silico simulation results 138
5.2.3.1 Results for GANPD 138
5.2.3.2 Results for GAMPD 166
5.3 PCR-CTPP primer design 194
5.3.1 Datasets and environment 194
5.3.2 Parameter settings for PCR-CTPP primer design 194
5.3.3 Results for computational simulated experiments of PCR-CTPP primer design 195
5.3.4 Genotyping experiment 211
5.4 An updated and integrated PCR-RFLP tool for SNP genotyping (SNP-RFLPing 2) 213
5.4.1 Original functions in SNP-RFLPing (ver. 1) and their improvements 213
5.4.2 New improvements in SNP-RFLPing 2 215
5.4.3 Common output examples for SNP-RFLPing 2 218
5.5 SNP ID-centric retrieval for flanking sequences (SNP-Flankplus) 223
5.5.1 Input 223
5.5.2 Output 225
5.5.3 A tool for integrated to SNP related primer design 226
5.6 A primer designer for cost-effective SNP genotyping (Prim-SNPing) 227
5.6.1 Input 227
5.6.2 Output 230
5.6.3 Advantages of Prim-SNPing 233
5.7 An improved and visualized COBRA software for epigenomic studies (Methyl-Typing) 235
5.7.1 Input 235
5.7.2 Analysis 237
5.7.3 Output 237
5.7.4 Experimental results 242
5.7.5 Advantages of Methyl-Typing 243
5.8 Drug-, protein interaction- and tagSNP-integrated SNP retrieval and genotyping tool (Drug-SNPing) 246
5.8.1 Input 246
5.8.2 Output 248
5.8.3 The importance of Drug-SNPing 254
VI. CONCLUSION 256
VII. FUTURE WORKS 260
REFERENCES 262
APPENDIX I. List of abbreviations 283
APPENDIX II. Related links 285
APPENDIX III. The available bioinformatics related systems and resources in the dissertation 287
APPENDIX IV. User manuals 290
APPENDIX V. Publication list 291

1.Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N: Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985, 230:1350-1354.
2.Mullis KB, Faloona FA: Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods in enzymology 1987, 155:335.
3.McPherson MJ, Hames BD, Taylor GR: PCR 2: a practical approach: Oxford University Press, USA; 1995.
4.Kämpke T, Kieninger M, Mecklenburg M: Efficient primer design algorithms. Bioinformatics 2001, 17(3):214-225.
5.Rozen S, Skaletsky H: Primer3 on the WWW for general users and for biologist programmers. Methods in Molecular Biology 2000, 132(3):365-386.
6.Sambrook J, Russell DW: Molecular cloning: a laboratory manual: CSHL press; 2001.
7.Wu JS, Lee C, Wu CC, Shiue YL: Primer design using genetic algorithm. Bioinformatics 2004, 20(11):1710-1717.
8.Vallone PM, Butler JM: AutoDimer: a screening tool for primer-dimer and hairpin structures. BioTechniques 2004, 37(2):226-231.
9.Chen SH, Lin CY, Cho CS, Lo CZ, Hsiung CA: Primer Design Assistant (PDA): A web-based primer design tool. Nucleic acids research 2003, 31(13):3751-3754.
10.Hsieh MH, Hsu WC, Chiu SK, Tzeng CM: An efficient algorithm for minimal primer set selection. Bioinformatics 2003, 19(2):285-286.
11.Rose TM, Henikoff JG, Henikoff S: CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) PCR primer design. Nucleic acids research 2003, 31(13):3763-3766.
12.Wang J, Li KB, Sung WK: G-PRIMER: greedy algorithm for selecting minimal primer set. Bioinformatics 2004, 20(15):2473-2475.
13.Liu S, Tinker NA, Molnar SJ, Mather DE: EC_oligos: automated and whole-genome primer design for exons within one or between two genomes. Bioinformatics 2004, 20(18):3668-3669.
14.Miura F, Uematsu C, Sakaki Y, Ito T: A novel strategy to design highly specific PCR primers based on the stability and uniqueness of 3'-end subsequences. Bioinformatics 2005, 21(24):4363-4370.
15.Andersson A, Bernander R, Nilsson P: Dual-genome primer design for construction of DNA microarrays. Bioinformatics 2005, 21(3):325-332.
16.Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG: The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic acids research 1997, 25(24):4876-4882.
17.Maddison DR, Swofford DL, Maddison WP: NEXUS: an extensible file format for systematic information. Systematic biology 1997, 46(4):590-621.
18.Rice P, Longden I, Bleasby A: EMBOSS: the European Molecular Biology Open Software Suite. Trends Genet 2000, 16(6):276-277.
19.Felsenstein J: PHYLIP (Phylogeny Inference Package) version 3.6. Distributed by the author Department of Genome Sciences, University of Washington, Seattle 2004.
20.Gadberry MD, Malcomber ST, Doust AN, Kellogg EA: Primaclade--a flexible tool to find conserved PCR primers across multiple species. Bioinformatics 2005, 21(7):1263-1264.
21.Untergasser A, Nijveen H, Rao X, Bisseling T, Geurts R, Leunissen JA: Primer3Plus, an enhanced web interface to Primer3. Nucleic acids research 2007, 35(Web Server issue):W71-74.
22.Kim N, Lee C: QPRIMER: a quick web-based application for designing conserved PCR primers from multigenome alignments. Bioinformatics 2007, 23(17):2331-2333.
23.Bekaert M, Teeling EC: UniPrime: a workflow-based platform for improved universal primer design. Nucleic acids research 2008, 36(10):e56.
24.Qu W, Shen Z, Zhao D, Yang Y, Zhang C: MFEprimer: multiple factor evaluation of the specificity of PCR primers. Bioinformatics 2009, 25(2):276-278.
25.Boutros R, Stokes N, Bekaert M, Teeling EC: UniPrime2: a web service providing easier Universal Primer design. Nucleic acids research 2009, 37(Web Server issue):W209-213.
26.Contreras-Moreira B, Sachman-Ruiz B, Figueroa-Palacios I, Vinuesa P: primers4clades: a web server that uses phylogenetic trees to design lineage-specific PCR primers for metagenomic and diversity studies. Nucleic acids research 2009, 37(Web Server issue):W95-W100.
27.Yang C-H, Cheng Y-H, Chang H-W, Chuang L-Y: Primer design with specific PCR product size using Memetic algorithm. IEEE Conference on Soft Computing in Industrial Applications 2008:332-337.
28.Yang CH, Cheng YH, Chuang LY, Chang HW: Specific PCR product primer design using memetic algorithm. Biotechnology progress 2009, 25(3):745-753.
29.Yang CH, Cheng YH, Chang HW, Chuang LY: Primer Design with Specific PCR Product using Particle Swarm Optimization. International Journal of Chemical and Biomolecular Engineering 2010, 3(1):18-23.
30.Yang CH, Cheng YH, Chang HW, Chuang LY: Fuzzy adaptive particle swarm optimization for a specific primer design problem. IEEE International Conference on Fuzzy Systems 2009:1021-1026.
31.Yang C-H, Cheng Y-H, Chuang L-Y, Yang C-H: Chaotic Inertia Weight Particle Swarm Optimization for PCR Primer Design. In: The 4th International Symposium on Bio- and Medical Informatics and Cybernetics: BMIC 2010. Orlando, Florida, USA; 2010.
32.Yang C-H, Cheng Y-H, Yang C-H: PCR Primer Design using Particle Swarm Optimization combined with Piecewise Linear Chaotic Map. In: International Conference on Soft Computing, Intelligent System and Information Technology (2nd ICSIIT 2010). Bali, Indonesia; 2010.
33.Anzick SL, Trent JM: Role of genomics in identifying new targets for cancer therapy. Oncology (Williston Park, NY 2002, 16(5 Suppl 4):7-13.
34.Inoue I: [SNP database and establishment of personalized medicine]. Nippon yakurigaku zasshi 2002, 120(1):41P-42P.
35.Imyanitov EN, Togo AV, Hanson KP: Searching for cancer-associated gene polymorphisms: promises and obstacles. Cancer letters 2004, 204(1):3-14.
36.Efferth T, Volm M: Pharmacogenetics for individualized cancer chemotherapy. Pharmacology & therapeutics 2005, 107(2):155-176.
37.Hemminki K, Forsti A, Bermejo L: Single nucleotide polymorphisms(SNPs) are inherited from parents and they measure heritable events. Journal of Carcinogenesis 2005, 4(1):2.
38.Robert J, Morvan VL, Smith D, Pourquier P, Bonnet J: Predicting drug response and toxicity based on gene polymorphisms. Critical reviews in oncology/hematology 2005, 54(3):171-196.
39.NCBI: dbSNP Overview. http://www.ncbi.nlm.nih.gov/SNP/get_html.cgi?whichHtml=overview (accessed April 2010).
40.Hacia JG, Fan JB, Ryder O, Jin L, Edgemon K, Ghandour G, Mayer RA, Sun B, Hsie L, Robbins CM et al: Determination of ancestral alleles for human single-nucleotide polymorphisms using high-density oligonucleotide arrays. Nature genetics 1999, 22(2):164-167.
41.Mooser V, Waterworth DM, Isenhour T, Middleton L: Cardiovascular pharmacogenetics in the SNP era. J Thromb Haemost 2003, 1(7):1398-1402.
42.Erichsen HC, Chanock SJ: SNPs in cancer research and treatment. British journal of cancer 2004, 90(4):747-751.
43.Engle LJ, Simpson CL, Landers JE: Using high-throughput SNP technologies to study cancer. Oncogene 2006, 25(11):1594-1601.
44.Cantor CR: The use of genetic SNPs as new diagnostic markers in preventive medicine. Annals of the New York Academy of Sciences 2005, 1055(1):48-57.
45.Bernig T, Chanock SJ: Challenges of SNP genotyping and genetic variation: its future role in diagnosis and treatment of cancer. Expert Review of Molecular Diagnostics 2006, 6(3):319-331.
46.Sadee W: Pharmacogenomics: Harbinger for the Era of Personalized Medicine? Molecular Interventions 2005, 5(3):140-143.
47.Divne AM, Allen M: A DNA microarray system for forensic SNP analysis. Forensic science international 2005, 154(2-3):111-121.
48.Jasmine F, Ahsan H, Andrulis IL, John EM, Chang-Claude J, Kibriya MG: Whole-genome amplification enables accurate genotyping for microarray-based high-density single nucleotide polymorphism array. Cancer Epidemiol Biomarkers Prev 2008, 17(12):3499-3508.
49.Sober S, Org E, Kepp K, Juhanson P, Eyheramendy S, Gieger C, Lichtner P, Klopp N, Veldre G, Viigimaa M et al: Targeting 160 candidate genes for blood pressure regulation with a genome-wide genotyping array. PloS one 2009, 4(6):e6034.
50.Griffin TJ, Smith LM: Single-nucleotide polymorphism analysis by MALDI-TOF mass spectrometry. Trends in biotechnology 2000, 18(2):77-84.
51.Hui L, DelMonte T, Ranade K: Genotyping using the TaqMan assay. Curr Protoc Hum Genet 2008, Chapter 2:Unit 2 10.
52.Borgiani P, Ciccacci C, Forte V, Sirianni E, Novelli L, Bramanti P, Novelli G: CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population. Pharmacogenomics 2009, 10(2):261-266.
53.Zhang J, Wheeler DA, Yakub I, Wei S, Sood R, Rowe W, Liu PP, Gibbs RA, Buetow KH: SNPdetector: a software tool for sensitive and accurate SNP detection. PLoS computational biology 2005, 1(5):e53.
54.Kwok PY: SNP genotyping with fluorescence polarization detection. Human mutation 2002, 19(4):315-323.
55.Olivier M: The Invader assay for SNP genotyping. Mutation research 2005, 573(1-2):103-110.
56.Ahmadian A, Ehn M, Hober S: Pyrosequencing: history, biochemistry and future. Clinica chimica acta; international journal of clinical chemistry 2006, 363(1-2):83-94.
57.Chang HW, Yang CH, Chang PL, Cheng YH, Chuang LY: SNP-RFLPing: restriction enzyme mining for SNPs in genomes. BMC genomics 2006, 7:30.
58.Yen CY, Liu SY, Chen CH, Tseng HF, Chuang LY, Yang CH, Lin YC, Wen CH, Chiang WF, Ho CH et al: Combinational polymorphisms of four DNA repair genes XRCC1, XRCC2, XRCC3, and XRCC4 and their association with oral cancer in Taiwan. J Oral Pathol Med 2008, 37(5):271-277.
59.Aomori T, Yamamoto K, Oguchi-Katayama A, Kawai Y, Ishidao T, Mitani Y, Kogo Y, Lezhava A, Fujita Y, Obayashi K et al: Rapid single-nucleotide polymorphism detection of cytochrome P450 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genes for the warfarin dose adjustment by the SMart-amplification process version 2. Clin Chem 2009, 55(4):804-812.
60.Lin GT, Tseng HF, Yang CH, Hou MF, Chuang LY, Tai HT, Tai MH, Cheng YH, Wen CH, Liu CS et al: Combinational Polymorphisms of Seven CXCL12-Related Genes Are Protective against Breast Cancer in Taiwan. Omics 2009.
61.Chang HW, Cheng YH, Chuang LY, Yang CH: SNP-RFLPing 2: an updated and integrated PCR-RFLP tool for SNP genotyping. BMC bioinformatics 2010, 11(1):173.
62.Demirci FY, Manzi S, Ramsey-Goldman R, Kenney M, Shaw PS, Dunlop-Thomas CM, Kao AH, Rhew EY, Bontempo F, Kammerer C et al: Association study of Toll-like receptor 5 (TLR5) and Toll-like receptor 9 (TLR9) polymorphisms in systemic lupus erythematosus. The Journal of rheumatology 2007, 34(8):1708-1711.
63.Chuang LY, Yang CH, Cheng YH, Gu DL, Chang PL, Tsui KH, Chang HW: V-MitoSNP: visualization of human mitochondrial SNPs. BMC bioinformatics 2006, 7:379.
64.Roberts RJ, Vincze T, Posfai J, Macelis D: REBASE--enzymes and genes for DNA restriction and modification. Nucleic acids research 2007, 35(Database issue):D269-270.
65.Roberts RJ, Vincze T, Posfai J, Macelis D: REBASE--a database for DNA restriction and modification: enzymes, genes and genomes. Nucleic acids research 2010, 38(Database issue):D234-236.
66.Chang HW, Chuang LY, Cheng YH, Hung YC, Wen CH, Gu DL, Yang CH: Prim-SNPing: a primer designer for cost-effective SNP genotyping. BioTechniques 2009, 46(6):421-431.
67.Chang HW, Chuang LY, Chang YJ, Cheng YH, Hung YC, Chen HC, Yang CH: LD2SNPing: linkage disequilibrium plotter and RFLP enzyme mining for tag SNPs. BMC genetics 2009, 10:26.
68.Zhang R, Zhu Z, Zhu H, Nguyen T, Yao F, Xia K, Liang D, Liu C: SNP Cutter: a comprehensive tool for SNP PCR-RFLP assay design. Nucleic acids research 2005, 33(Web Server issue):W489-492.
69.Vincze T, Posfai J, Roberts RJ: NEBcutter: A program to cleave DNA with restriction enzymes. Nucleic acids research 2003, 31(13):3688-3691.
70.Ke X, Collins A, Ye S: PIRA PCR designer for restriction analysis of single nucleotide polymorphisms. Bioinformatics 2001, 17(9):838-839.
71.NCBI: Restriction Fragment Length Polymorphism (RFLP). http://www.ncbi.nlm.nih.gov/genome/probe/doc/TechRFLP.shtml (accessed September 2009).
72.Chuang LY, Yang CH, Tsui KH, Cheng YH, Chang PL, Wen CH, Chang HW: Restriction enzyme mining for SNPs in genomes. Anticancer research 2008, 28(4A):2001-2007.
73.Hellman A, Chess A: Extensive sequence-influenced DNA methylation polymorphism in the human genome. Epigenetics & chromatin 2010, 3(1):11.
74.Tost J: DNA methylation: an introduction to the biology and the disease-associated changes of a promising biomarker. Methods Mol Biol 2009, 507:3-20.
75.Sherry ST, Ward M, Sirotkin K: Use of molecular variation in the NCBI dbSNP database. Human mutation 2000, 15(1):68-75.
76.Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K: dbSNP: the NCBI database of genetic variation. Nucleic acids research 2001, 29(1):308-311.
77.Pruitt KD, Tatusova T, Maglott DR: NCBI Reference Sequence project: update and current status. Nucleic acids research 2003, 31(1):34-37.
78.Pruitt KD, Tatusova T, Maglott DR: NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic acids research 2005, 33(Database issue):D501-504.
79.Pruitt KD, Tatusova T, Maglott DR: NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic acids research 2007, 35(Database issue):D61-65.
80.Pruitt KD, Tatusova T, Klimke W, Maglott DR: NCBI Reference Sequences: current status, policy and new initiatives. Nucleic acids research 2009, 37(Database issue):D32-36.
81.CGAP: All About the CGAP GO Browser. http://cgap.nci.nih.gov/Genes/AllAboutGO (accessed April 2010).
82.Packer BR, Yeager M, Burdett L, Welch R, Beerman M, Qi L, Sicotte H, Staats B, Acharya M, Crenshaw A et al: SNP500Cancer: a public resource for sequence validation, assay development, and frequency analysis for genetic variation in candidate genes. Nucleic acids research 2006, 34(Database issue):D617-621.
83.Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, Chang Z, Woolsey J: DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic acids research 2006, 34(Database issue):D668-672.
84.Wishart DS: DrugBank and its relevance to pharmacogenomics. Pharmacogenomics 2008, 9(8):1155-1162.
85.Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic acids research 2008, 36(Database issue):D901-906.
86.NCBI: dbSNP Summary. http://www.ncbi.nlm.nih.gov/SNP/snp_summary.cgi (accessed April 2010).
87.NCBI: The Reference Sequence (RefSeq) Project. http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=handbook&part=ch18 (accessed April 2010).
88.REBASE: REBASE HELP. http://rebase.neb.com/rebase/rebhelp.html (accessed April 2010).
89.CGAP: SNP500Cancer: Background Information. http://snp500cancer.nci.nih.gov/background.cfm (accessed April 2010).
90.DrugBank: About DrugBank. http://www.drugbank.ca/about (accessed April 2010).
91.Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S, Madden TL: NCBI BLAST: a better web interface. Nucleic acids research 2008, 36(Web Server issue):W5-9.
92.UCSC: UCSC In-Silico PCR. http://genome.ucsc.edu/cgi-bin/hgPcr (accessed April 2010).
93.Thorisson GA, Smith AV, Krishnan L, Stein LD: The International HapMap Project Web site. Genome research 2005, 15(11):1592-1593.
94.de Bakker PI: Selection and evaluation of Tag-SNPs using Tagger and HapMap. CSH protocols 2009, 2009(6):pdb ip67.
95.Jensen LJ, Kuhn M, Stark M, Chaffron S, Creevey C, Muller J, Doerks T, Julien P, Roth A, Simonovic M et al: STRING 8--a global view on proteins and their functional interactions in 630 organisms. Nucleic acids research 2009, 37(Database issue):D412-416.
96.NCBI: BLAST. http://blast.ncbi.nlm.nih.gov/Blast.cgi (accessed April 2010).
97.STRING: STRING 8.2. http://string.embl.de/ (accessed April 2010).
98.Holland J: Adaptation in Nature and Artificial Systems: MIT Press; 1992.
99.Chang HW, Chuang LY, Ho CH, Chang PL, Yang CH: Odds ratio-based genetic algorithms for generating SNP barcodes of genotypes to predict disease susceptibility. Omics 2008, 12(1):71-81.
100.Oh IS, Lee JS, Moon BR: Hybrid genetic algorithms for feature selection. IEEE transactions on pattern analysis and machine intelligence 2004, 26(11):1424-1437.
101.Dawkins R: The Selfish Gene: Oxford University Press, USA; 2006.
102.Moscato P: On evolution, search, optimization, genetic algorithms and martial arts: Towards memetic algorithms. In. Tech. Rep. Caltech Concurrent Computation Program, Rep. 826, California Inst. Technol., Pasadena, CA; 1989.
103.Merz P, Freisleben B: A Genetic Local Search Approach to the Quadratic Assignment Problem. In: The Seventh International Conference on Genetic Algorithms. 1997: 465–472.
104.Nguyen QH, Ong YS, Lim MH: A probabilistic memetic framework. In., vol. 13: Institute of Electrical and Electronics Engineers Inc., The; 2009: 604-623.
105.Torn A, Zilinskas A: Global Optimization, vol. 350. New York: Springer-Verlag; 1989.
106.Radcliffe NJ, Surry PD: Formal memetic algorithms. In., vol. 865: Springer; 1994: 1-16.
107.Ong YS, Keane AJ: Meta-Lamarckian learning in memetic algorithms. IEEE Transactions on Evolutionary Computation 2004, 8(2):99-110.
108.Hasan SMK, Sarker R, Essam D, Cornforth D: Memetic algorithms for solving job-shop scheduling problems. Memetic Computing 2009, 1(1):69-83.
109.Zhu Z, Ong Y, Dash M: Wrapper-filter feature selection algorithm using a memetic framework. IEEE Trans Syst Man Cybern B Cybern 2007, 37(1):70.
110.Tang M, Yao X: A memetic algorithm for VLSI floorplanning. IEEE Trans Syst Man Cybern B Cybern 2007, 37(1):62-69.
111.Tang J, Lim MH, Ong YS: Diversity-adaptive parallel memetic algorithm for solving large scale combinatorial optimization problems. Soft Computing - A Fusion of Foundations, Methodologies and Applications 2007, 11(9):873-888.
112.Kennedy J, Eberhart R: Particle swarm optimization. IEEE International Conference on Neural Networks 1995, 4:1942-1948.
113.Kennedy J, Eberhart RC: A discrete binary version of the particle swarm algorithm. IEEE International Conference on Systems, Man and Cybernetics 1997, 5:4104-4108.
114.Kennedy JF, Eberhart RC, Shi Y: Swarm intelligence. US: Springer; 2001.
115.Shi Y, Eberhart RC: Empirical study of particle swarm optimization. IEEE Congress on Evolutionary Computation 1999, 3:1948-1950.
116.Eberhart RC, Shi Y: Tracking and optimizing dynamic systems with particle swarms. Proceedings of the IEEE Congress on Evolutionary Computation 2001, 1:94-97.
117.Shi Y, Eberhart RC, Team E, Kokomo IN: Fuzzy adaptive particle swarm optimization. Proceedings of IEEE International Conference on Evolutionary Computation 2001, 1:101-106.
118.Shi Y, Eberhart R, Chen Y: Implementation of evolutionary fuzzy systems. IEEE Transactions on Fuzzy Systems 1999, 7(2):109-119.
119.Kellert SH: In the wake of chaos: Unpredictable order in dynamical systems: University of Chicago Press; 1993.
120.Schuster HG, Just W: Deterministic chaos: an introduction: Wiley-VCH Verlag GmbH; 2005.
121.Parker TS, Chua LO: Chaos: A tutorial for engineers. Proceedings of the IEEE 1987, 75(8):982-1008.
122.Heidari-Bateni G, McGillem CD, Lcc A: A chaotic direct-sequence spread-spectrum communication system. IEEE transactions on communications 1994, 42(234 Part 3):1524-1527.
123.Chuanwen J, Bompard E: A hybrid method of chaotic particle swarm optimization and linear interior for reactive power optimisation. Mathematics and Computers in Simulation 2005, 68(1):57-65.
124.Wallace RB, Shaffer J, Murphy RF, Bonner J, Hirose T, Itakura K: Hybridization of synthetic oligodeoxyribonucleotides to phi chi 174 DNA: the effect of single base pair mismatch. Nucleic acids research 1979, 6(11):3543-3557.
125.Sambrook J, Fritsch EF, Maniatis T: Molecular cloning: Cold Spring Harbor Laboratory Press Cold Spring Harbor, NY; 1989.
126.Baranovsky A, Daems D: Design of one-dimensional chaotic maps with prescribed statistical properties. International Journal of Bifurcation and Chaos 1995, 5(6):1585-1598.
127.Xiang T, Liao X, Wong K: An improved particle swarm optimization algorithm combined with piecewise linear chaotic map. Applied Mathematics and Computation 2007, 190(2):1637-1645.
128.Bao L, Zhou M, Wu L, Lu L, Goldowitz D, Williams RW, Cui Y: PolymiRTS Database: linking polymorphisms in microRNA target sites with complex traits. Nucleic acids research 2007, 35(Database issue):D51-54.
129.Yang CH, Cheng YH, Chuang LY, Chang HW: SNP-Flankplus: SNP ID-centric retrieval for SNP flanking sequences. Bioinformation 2008, 3(4):147-149.
130.Yang CH, Chuang LY, Cheng YH, Gu DL, Chen CH, Chang HW: Methyl-Typing: an improved and visualized COBRA software for epigenomic studies. FEBS letters 2009, 584(4):739-744.
131.Bao L, Zhou M, Cui Y: CTCFBSDB: a CTCF-binding site database for characterization of vertebrate genomic insulators. Nucleic acids research 2008, 36(Database issue):D83-87.
132.Gaszner M, Felsenfeld G: Insulators: exploiting transcriptional and epigenetic mechanisms. Nat Rev Genet 2006, 7(9):703-713.
133.Karolchik D, Kuhn RM, Baertsch R, Barber GP, Clawson H, Diekhans M, Giardine B, Harte RA, Hinrichs AS, Hsu F et al: The UCSC Genome Browser Database: 2008 update. Nucleic acids research 2008, 36(Database issue):D773-779.
134.Wakaguri H, Yamashita R, Suzuki Y, Sugano S, Nakai K: DBTSS: database of transcription start sites, progress report 2008. Nucleic acids research 2008, 36(Database issue):D97-101.
135.Takai D, Jones PA: The CpG island searcher: a new WWW resource. In Silico Biol 2003, 3(3):235-240.
136.Elbeltagi E, Hegazy T, Grierson D: Comparison among five evolutionary-based optimization algorithms. Advanced Engineering Informatics 2005, 19(1):43-53.
137.Moscato P, Norman MG: A Memetic Approach for the Traveling Salesman Problem Implementation of a Computational Ecology for Combinatorial Optimization on Message-Passing Systems. Parallel Computing and Transputer Applications 1992:177-186.
138.Angeline PJ: Evolutionary optimization versus particle swarm optimization: Philosophy and performance differences. Proceedings of the Seventh Annual Conference on Evolutionary Programming 1998:601-610.
139.Jiang Y, Hu T, Huang CC, Wu X: An improved particle swarm optimization algorithm. Applied Mathematics and Computation 2007, 193(1):231-239.
140.Yang X, Yuan J, Yuan J, Mao H: A modified particle swarm optimizer with dynamic adaptation. Applied Mathematics and Computation 2007, 189(2):1205-1213.
141.Liu B, Wang L, Jin YH, Tang F, Huang DX: Improved particle swarm optimization combined with chaos. Chaos, Solitons and Fractals 2005, 25(5):1261-1271.
142.Tsoukalas LH, Uhrig RE: Fuzzy and neural approaches in engineering: John Wiley & Sons, Inc. New York, NY, USA; 1996.
143.Goldberg TE, Kotov R, Lee AT, Gregersen PK, Lencz T, Bromet E, Malhotra AK: The serotonin transporter gene and disease modification in psychosis: Evidence for systematic differences in allelic directionality at the 5-HTTLPR locus. Schizophr Res 2009, 111(1-3):103-108.
144.Mandelli L, Mazza M, Martinotti G, Di Nicola M, Tavian D, Colombo E, Missaglia S, De Ronchi D, Colombo R, Janiri L: Harm avoidance moderates the influence of serotonin transporter gene variants on treatment outcome in bipolar patients. J Affect Disord 2009, 119(1-3):205-209.
145.Sakurai T, Reichert J, Hoffman EJ, Cai G, Jones HB, Faham M, Buxbaum JD: A large-scale screen for coding variants in SERT/SLC6A4 in autism spectrum disorders. Autism Res 2008, 1(4):251-257.
146.De Jong KA, Spears WM: An analysis of the interacting roles of population size and crossover in genetic algorithms, vol. 496: Springer Berlin / Heidelberg; 1990.
147.Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Sayers EW: GenBank. Nucleic acids research 2009, 37(Database issue):D26-31.
148.Chang HW, Chuang LY, Cheng YH, Ho CH, Wen CH, Yang CH: Seq-SNPing: multiple-alignment tool for SNP discovery, SNP ID identification, and RFLP genotyping. Omics 2009, 13(3):253-260.
149.Altshuler D, Brooks LD, Chakravarti A, Collins FS, Daly MJ, Donnelly P: A haplotype map of the human genome. Nature 2005, 437(7063):1299-1320.
150.Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE et al: Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 2007, 447(7146):799-816.
151.Ambros V: The functions of animal microRNAs. Nature 2004, 431(7006):350-355.
152.Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116(2):281-297.
153.Migliore C, Giordano S: MiRNAs as new master players. Cell Cycle 2009, 8(14):2185-2186.
154.Mishra PJ, Bertino JR: MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. Pharmacogenomics 2009, 10(3):399-416.
155.Kang HJ, Choi KO, Kim BD, Kim S, Kim YJ: FESD: a Functional Element SNPs Database in human. Nucleic acids research 2005, 33(Database issue):D518-522.
156.Hamajima N: PCR-CTPP: a new genotyping technique in the era of genetic epidemiology. Expert Rev Mol Diagn 2001, 1(1):119-123.
157.Niu T, Hu Z: SNPicker: a graphical tool for primer picking in designing mutagenic endonuclease restriction assays. Bioinformatics 2004, 20(17):3263-3265.
158.Xu YH, Manoharan HT, Pitot HC: CpG analyzer, a Windows-based utility program for investigation of DNA methylation. BioTechniques 2005, 39(5):656, 658, 660 passim.
159.Rohde C, Zhang Y, Jurkowski TP, Stamerjohanns H, Reinhardt R, Jeltsch A: Bisulfite sequencing Data Presentation and Compilation (BDPC) web server--a useful tool for DNA methylation analysis. Nucleic acids research 2008, 36(5):e34.
160.Bock C, Reither S, Mikeska T, Paulsen M, Walter J, Lengauer T: BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing. Bioinformatics 2005, 21(21):4067-4068.
161.Grunau C, Schattevoy R, Mache N, Rosenthal A: MethTools--a toolbox to visualize and analyze DNA methylation data. Nucleic acids research 2000, 28(5):1053-1058.
162.Hetzl J, Foerster AM, Raidl G, Mittelsten Scheid O: CyMATE: a new tool for methylation analysis of plant genomic DNA after bisulphite sequencing. Plant J 2007, 51(3):526-536.
163.Xu YH, Manoharan HT, Pitot HC: CpG PatternFinder: a Windows-based utility program for easy and rapid identification of the CpG methylation status of DNA. BioTechniques 2007, 43(3):334, 336-340, 342.
164.Kumaki Y, Oda M, Okano M: QUMA: quantification tool for methylation analysis. Nucleic acids research 2008, 36(Web Server issue):W170-175.
165.Schuffler P, Mikeska T, Waha A, Lengauer T, Bock C: MethMarker: user-friendly design and optimization of gene-specific DNA methylation assays. Genome Biol 2009, 10(10):R105.
166.Doskocil J, Sorm F: Distribution of 5-methylcytosine in pyrimidine sequences of deoxyribonucleic acids. Biochim Biophys Acta 1962, 55:953-959.
167.Grippo P, Iaccarino M, Parisi E, Scarano E: Methylation of DNA in developing sea urchin embryos. J Mol Biol 1968, 36(2):195-208.
168.Simon D, Grunert F, von Acken U, Doring HP, Kroger H: DNA-methylase from regenerating rat liver: purification and characterisation. Nucleic acids research 1978, 5(6):2153-2167.
169.Pontecorvo G, De Felice B, Carfagna M: Novel methylation at GpC dinucleotide in the fish Sparus aurata genome. Mol Biol Rep 2000, 27(4):225-230.
170.Kouidou S, Malousi A, Maglaveras N: Methylation and repeats in silent and nonsense mutations of p53. Mutation research 2006, 599(1-2):167-177.
171.Rodenhiser D, Chakraborty P, Andrews J, Ainsworth P, Mancini D, Lopes E, Singh S: Heterogenous point mutations in the BRCA1 breast cancer susceptibility gene occur in high frequency at the site of homonucleotide tracts, short repeats and methylatable CpG/CpNpG motifs. Oncogene 1996, 12(12):2623-2629.
172.Ramsahoye BH, Biniszkiewicz D, Lyko F, Clark V, Bird AP, Jaenisch R: Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc Natl Acad Sci U S A 2000, 97(10):5237-5242.
173.Horard B, Eymery A, Fourel G, Vassetzky N, Puechberty J, Roizes G, Lebrigand K, Barbry P, Laugraud A, Gautier C et al: Global analysis of DNA methylation and transcription of human repetitive sequences. Epigenetics 2009, 4(5):339-350.
174.Lee HS, Kim BH, Cho NY, Yoo EJ, Choi M, Shin SH, Jang JJ, Suh KS, Kim YS, Kang GH: Prognostic implications of and relationship between CpG island hypermethylation and repetitive DNA hypomethylation in hepatocellular carcinoma. Clin Cancer Res 2009, 15(3):812-820.
175.Sun LZ, Ji ZL, Chen X, Wang JF, Chen YZ: ADME-AP: a database of ADME associated proteins. Bioinformatics 2002, 18(12):1699-1700.
176.Hug H, Bagatto D, Dannecker R, Schindler R, Horlacher O, Gut J: ADRIS--The Adverse Drug Reactions Information Scheme. Pharmacogenetics 2003, 13(12):767-772.
177.Mattingly CJ, Colby GT, Forrest JN, Boyer JL: The Comparative Toxicogenomics Database (CTD). Environ Health Perspect 2003, 111(6):793-795.
178.Tong W, Cao X, Harris S, Sun H, Fang H, Fuscoe J, Harris A, Hong H, Xie Q, Perkins R: Arraytrack-Supporting Toxicogenomic Research at the US Food and Drug Administration National Center for Toxicological Research. Environ Health Perspect 2003, 111(15):1819-1827.
179.Burgarella S, Cattaneo D, Pinciroli F, Masseroli M: MicroGen: a MIAME compliant web system for microarray experiment information and workflow management. BMC bioinformatics 2005, 6 Suppl 4:S6.
180.Freimuth RR, Stormo GD, McLeod HL: PolyMAPr: programs for polymorphism database mining, annotation, and functional analysis. Human mutation 2005, 25(2):110-117.
181.Hayes KR, Vollrath AL, Zastrow GM, McMillan BJ, Craven M, Jovanovich S, Rank DR, Penn S, Walisser JA, Reddy JK et al: EDGE: a centralized resource for the comparison, analysis, and distribution of toxicogenomic information. Molecular pharmacology 2005, 67(4):1360-1368.
182.Salter AH: Large-scale databases in toxicogenomics. Pharmacogenomics 2005, 6(7):749-754.
183.Burgoon LD, Boutros PC, Dere E, Zacharewski TR: dbZach: A MIAME-compliant toxicogenomic supportive relational database. Toxicol Sci 2006, 90(2):558-568.
184.Mattingly CJ, Rosenstein MC, Colby GT, Forrest JN, Jr., Boyer JL: The Comparative Toxicogenomics Database (CTD): a resource for comparative toxicological studies. Journal of experimental zoology 2006, 305(9):689-692.
185.Xirasagar S, Gustafson SF, Huang CC, Pan Q, Fostel J, Boyer P, Merrick BA, Tomer KB, Chan DD, Yost KJ, 3rd et al: Chemical effects in biological systems (CEBS) object model for toxicology data, SysTox-OM: design and application. Bioinformatics 2006, 22(7):874-882.
186.Wishart DS: Human Metabolome Database: completing the 'human parts list'. Pharmacogenomics 2007, 8(7):683-686.
187.Zheng CJ, Han LY, Xie B, Liew CY, Ong S, Cui J, Zhang HL, Tang ZQ, Gan SH, Jiang L et al: PharmGED: Pharmacogenetic Effect Database. Nucleic acids research 2007, 35(Database issue):D794-799.
188.Sangkuhl K, Berlin DS, Altman RB, Klein TE: PharmGKB: understanding the effects of individual genetic variants. Drug metabolism reviews 2008, 40(4):539-551.
189.Gamazon ER, Duan S, Zhang W, Huang RS, Kistner EO, Dolan ME, Cox NJ: PACdb: a database for cell-based pharmacogenomics. Pharmacogenetics and genomics 2010, 20(4):269-273.
190.Chen J, Swamidass SJ, Dou Y, Bruand J, Baldi P: ChemDB: a public database of small molecules and related chemoinformatics resources. Bioinformatics 2005, 21(22):4133-4139.
191.Miteva MA, Violas S, Montes M, Gomez D, Tuffery P, Villoutreix BO: FAF-Drugs: free ADME/tox filtering of compound collections. Nucleic acids research 2006, 34(Web Server issue):W738-744.
192.Neugebauer A, Hartmann RW, Klein CD: Prediction of protein-protein interaction inhibitors by chemoinformatics and machine learning methods. Journal of medicinal chemistry 2007, 50(19):4665-4668.
193.Wang H, Klinginsmith J, Dong X, Lee AC, Guha R, Wu Y, Crippen GM, Wild DJ: Chemical data mining of the NCI human tumor cell line database. Journal of chemical information and modeling 2007, 47(6):2063-2076.
194.Timmers LF, Pauli I, Caceres RA, de Azevedo WF, Jr.: Drug-binding databases. Current drug targets 2008, 9(12):1092-1099.
195.Masciocchi J, Frau G, Fanton M, Sturlese M, Floris M, Pireddu L, Palla P, Cedrati F, Rodriguez-Tome P, Moro S: MMsINC: a large-scale chemoinformatics database. Nucleic acids research 2009, 37(Database issue):D284-290.
196.Chen Y-J, Cheng Y-H, Yang C-H, Chuang L-Y: Memetic algorithm for primer design with specific PCR product size. In: Sixteenth Symposium on Recent Advances in Cellular and Molecular Biology. Pingtung, Taiwan; 2008: 236.
197.Voisey J, Morris CP: SNP technologies for drug discovery: a current review. Current drug discovery technologies 2008, 5(3):230-235.
198.Peters EJ, McLeod HL: Ability of whole-genome SNP arrays to capture 'must have' pharmacogenomic variants. Pharmacogenomics 2008, 9(11):1573-1577.
199.Royo JL, Galan JJ: Pyrosequencing for SNP genotyping. Methods Mol Biol 2009, 578:123-133.
200.Shen GQ, Abdullah KG, Wang QK: The TaqMan method for SNP genotyping. Methods Mol Biol 2009, 578:293-306.
201.Kocsis AK, Lakatos PL, Somogyvari F, Fuszek P, Papp J, Fischer S, Szamosi T, Lakatos L, Kovacs A, Hofner P et al: Association of beta-defensin 1 single nucleotide polymorphisms with Crohn's disease. Scandinavian journal of gastroenterology 2008, 43(3):299-307.
202.Yoshiya G, Takahata T, Hanada N, Suzuki K, Ishiguro A, Saito M, Sasaki M, Fukuda S: Influence of cancer-related gene polymorphisms on clinicopathological features in colorectal cancer. Journal of gastroenterology and hepatology 2008, 23(6):948-953.
203.Lin GT, Tseng HF, Chang CK, Chuang LY, Liu CS, Yang CH, Tu CJ, Wang EC, Tan HF, Chang CC et al: SNP combinations in chromosome-wide genes are associated with bone mineral density in Taiwanese women. The Chinese journal of physiology 2008, 51(1):32-41.
204.Zheng SL, Sun J, Wiklund F, Smith S, Stattin P, Li G, Adami HO, Hsu FC, Zhu Y, Balter K et al: Cumulative association of five genetic variants with prostate cancer. The New England journal of medicine 2008, 358(9):910-919.
205.Hamajima N, Saito T, Matsuo K, Tajima K: Competitive amplification and unspecific amplification in polymerase chain reaction with confronting two-pair primers. J Mol Diagn 2002, 4(2):103-107.
206.Ubeda JF, Fernandez-Gonzalez M, Briones AI: Application of PCR-TTGE and PCR-RFLP for intraspecific and interspecific characterization of the genus Saccharomyces using actin gene (ACT1) primers. Current Microbiology 2009, 58(1):58-63.
207.Tasleem Raza S, Husain N, Kumar A: Screening for hemophilia A carriers: utility of PCR-RFLP--based polymorphism analysis. Clin Appl Thromb Hemost 2009, 15(1):78-83.
208.Rojas M, Gonzalez I, Fajardo V, Martin I, Hernandez PE, Garcia T, Martin R: Polymerase chain reaction-restriction fragment length polymorphism authentication of raw meats from game birds. Journal of AOAC International 2008, 91(6):1416-1422.
209.Espineira M, Gonzalez-Lavin N, Vieites JM, Santaclara FJ: Authentication of anglerfish species (Lophius spp) by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and forensically informative nucleotide sequencing (FINS) methodologies. Journal of agricultural and food chemistry 2008, 56(22):10594-10599.
210.Costantini V, Guaricci AC, Laricchiuta P, Rausa F, Lacalandra GM: DNA sexing in Humboldt Penguins (Spheniscus humboldti) from feather samples. Animal reproduction science 2008, 106(1-2):162-167.
211.Yang C-H, Cheng Y-H, Chang H-W, Chuang L-Y: Primer design with specific PCR product using particle swarm optimization. In: ICCIT 2009: "International Conference on Computer and Information Technology". vol. 41. Tokyo, Japan: PROCEEDINGS OF WORLD ACADEMY OF SCIENCE, ENGINEERING AND TECHNOLOGY (PWASET) (ISSN: 2070-3740); 2009: 1449-1454.
212.Yang C-H, Cheng Y-H, Chuang L-Y: A natural PCR-RFLP primer design for SNP genotyping using a genetic algorithm. In: The International MultiConference of Engineers and Computer Scientists 2010. Hong Kong: Conference proceeding published by IAENG (ISBN: 978-988-17012-8-2); 2010: 124-129.
213.Yang C-H, Cheng Y-H, Chuang L-Y, Chang H-W: A Mismatch PCR-RFLP Primer Design for SNP Genotyping Using Genetic Algorithm. In: The 9th IEEE International Conference on Cognitive Informatics (ICCI 2010). Tsinghua University, Beijing, China; 2010.
214.Yang CH, Cheng YH, Chuang LY, Chang HW: Genetic Algorithm for the Design of Confronting Two-Pair Primers. Ninth IEEE international Conference on BioInformatics and BioEngineering (BIBE) 2009:242-247.
215.Yang C-H, Cheng Y-H, Chuang L-Y: Confronting Two-Pair Primer Design using Memetic Algorithm. In: The 27th workshop on Combinatorial Mathematics and Computation Theory. Providence University; 2010: 155-160.
216.Yang C-H, Cheng Y-H, Chuang L-Y, Chang H-W: SNP-Flankplus: SNP ID-centric retrieval of flanking sequences. In: The Twenty Second International Conference on Industrial, Engineering & Other Applications of Applied Intelligent Systems (IEA-AIE 2009). vol. 214. Tainan, Taiwan: Studies in Computational Intelligence, Opportunities and Challenges for Next-Generation Applied Intelligence (ISBN: 978-3-540-92813-3); 2009: 13-18.
217.Yang CH, Chuang LY, Cheng YH, Wen CH, Chang HW: Dynamic programming for single nucleotide polymorphism ID identification in systematic association studies. The Kaohsiung journal of medical sciences 2009, 25(4):165-176.
218.Yang CH, Chuang LY, Cheng YH, Wen CH, Chang PL, Chang HW: SNP ID-info: SNP ID searching and visualization platform. Omics 2008, 12(3):217-226.