Unraveling genomic variation from next generation sequencing data

BioData Mining

Georgios A Pavlopoulos²  Anastasis Oulas⁴  Ernesto Iacucci³  Alejandro Sifrim¹  Yves Moreau¹  Reinhard Schneider⁵  Jan Aerts¹  Ioannis Iliopoulos² 

[1] ESAT-SCD/iMinds-KU Leuven Future Health Department, University of Leuven, Kasteelpark Arenberg 10, box 2446, 3001 Leuven, Belgium

[2] Division of Basic Sciences, University of Crete Medical School, Heraklion 71110, Greece

[3] Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, Ghent, Belgium

[4] Institute of Marine Biology, Biotechnology and Aquaculture IMBBC-HCMR, Heraklion, Crete, Greece

[5] Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7 avenue des Hauts-Fourneaux, L-4362 Esch sur Alzette, Luxembourg

关键词: Genome wide association studies;    Polymorphisms;    Visualization;    Genome browser;    Sequencing;    Structural variation;    CNV;    SNVs;    SNPs;   

Others  :  797185
DOI  :  10.1186/1756-0381-6-13

 received in 2013-03-22, accepted in 2013-07-18,  发布年份 2013

【 摘 要 】

Elucidating the content of a DNA sequence is critical to deeper understand and decode the genetic information for any biological system. As next generation sequencing (NGS) techniques have become cheaper and more advanced in throughput over time, great innovations and breakthrough conclusions have been generated in various biological areas. Few of these areas, which get shaped by the new technological advances, involve evolution of species, microbial mapping, population genetics, genome-wide association studies (GWAs), comparative genomics, variant analysis, gene expression, gene regulation, epigenetics and personalized medicine. While NGS techniques stand as key players in modern biological research, the analysis and the interpretation of the vast amount of data that gets produced is a not an easy or a trivial task and still remains a great challenge in the field of bioinformatics. Therefore, efficient tools to cope with information overload, tackle the high complexity and provide meaningful visualizations to make the knowledge extraction easier are essential. In this article, we briefly refer to the sequencing methodologies and the available equipment to serve these analyses and we describe the data formats of the files which get produced by them. We conclude with a thorough review of tools developed to efficiently store, analyze and visualize such data with emphasis in structural variation analysis and comparative genomics. We finally comment on their functionality, strengths and weaknesses and we discuss how future applications could further develop in this field.

【 授权许可】

   
2013 Pavlopoulos et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 2.

Figure 8.

Figure 9.

【 参考文献 】

• [1]Finishing the euchromatic sequence of the human genome Nature 2004, 431(7011):931-945. PMID: 15496913
• [2]Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, et al.: Initial sequencing and analysis of the human genome. Nature 2001, 409(6822):860-921.
• [3]Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, Axelrod N, Huang J, Kirkness EF, Denisov G, et al.: The diploid genome sequence of an individual human. PLoS Biol 2007, 5(10):e254.
• [4]Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA: A map of human genome variation from population-scale sequencing. Nature 2010, 467(7319):1061-1073.
• [5]Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA: An integrated map of genetic variation from 1,092 human genomes. Nature 2012, 491(7422):56-65.
• [6]Buchanan CC, Torstenson ES, Bush WS, Ritchie MD: A comparison of cataloged variation between international HapMap consortium and 1000 genomes project data. J Am Med Inform Assoc 2012, 19(2):289-294.
• [7]Tanaka T: [International HapMap project]. Nihon Rinsho 2005, 12(63 Suppl):29-34.
• [8]Thorisson GA, Smith AV, Krishnan L, Stein LD: The international HapMap project Web site. Genome Res 2005, 15(11):1592-1593.
• [9]Integrating ethics and science in the international HapMap project Nat Rev Genet 2004, 5(6):467-475. PMID: 15153999
• [10]The international HapMap project Nature 2003, 426(6968):789-796. PMID: 14685227
• [11]Pitman NC, Jorgensen PM: Estimating the size of the world's threatened flora. Science 2002, 298(5595):989.
• [12]Weigel D, Mott R: The 1001 genomes project for arabidopsis thaliana. Genome Biol 2009, 10(5):107. BioMed Central Full Text
• [13]Genome 10K: a proposal to obtain whole-genome sequence for 10,000 vertebrate species J Hered 2009, 100(6):659-674. PMID: 19892720
• [14]Medini D, Donati C, Tettelin H, Masignani V, Rappuoli R: The microbial pan-genome. Curr Opin Genet Dev 2005, 15(6):589-594.
• [15]Cullum R, Alder O, Hoodless PA: The next generation: using new sequencing technologies to analyse gene regulation. Respirology 2011, 16(2):210-222.
• [16]Metzker ML: Sequencing technologies - the next generation. Nat Rev Genet 2010, 11(1):31-46.
• [17]Church M: Genomes for All. Sci Am 2006, 294:46-54.
• [18]Hall N: Advanced sequencing technologies and their wider impact in microbiology. J Exp Biol 2007, 210(Pt 9):1518-1525.
• [19]Nagarajan N, Pop M: Sequencing and genome assembly using next-generation technologies. Methods Mol Biol 2010, 673:1-17.
• [20]Git A, Dvinge H, Salmon-Divon M, Osborne M, Kutter C, Hadfield J, Bertone P, Caldas C: Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression. RNA 2010, 16(5):991-1006.
• [21]Hert DG, Fredlake CP, Barron AE: Advantages and limitations of next-generation sequencing technologies: a comparison of electrophoresis and non-electrophoresis methods. Electrophoresis 2008, 29(23):4618-4626.
• [22]Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, Wang M, Feng W, Zander T, MacConaill L, et al.: High-throughput oncogene mutation profiling in human cancer. Nat Genet 2007, 39(3):347-351.
• [23]Bennett S: Solexa Ltd. Pharmacogenomics 2004, 5(4):433-438.
• [24]Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, Hall KP, Evers DJ, Barnes CL, Bignell HR, et al.: Accurate whole human genome sequencing using reversible terminator chemistry. Nature 2008, 456(7218):53-59.
• [25]Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, Berka J, Braverman MS, Chen YJ, Chen Z, et al.: Genome sequencing in microfabricated high-density picolitre reactors. Nature 2005, 437(7057):376-380.
• [26]Luo C, Tsementzi D, Kyrpides N, Read T, Konstantinidis KT: Direct comparisons of illumina vs. Roche 454 sequencing technologies on the same microbial community DNA sample. PLoS One 2012, 7(2):e30087.
• [27]Liu L, Li Y, Li S, Hu N, He Y, Pong R, Lin D, Lu L, Law M: Comparison of next-generation sequencing systems. J Biomed Biotechnol 2012, 2012:251364.
• [28]Xu M, Fujita D, Hanagata N: Perspectives and challenges of emerging single-molecule DNA sequencing technologies. Small 2009, 5(23):2638-2649.
• [29]Wang Z, Gerstein M, Snyder M: RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 2009, 10(1):57-63.
• [30]Morin R, Bainbridge M, Fejes A, Hirst M, Krzywinski M, Pugh T, McDonald H, Varhol R, Jones S, Marra M: Profiling the HeLa S3 transcriptome using randomly primed cDNA and massively parallel short-read sequencing. Biotechniques 2008, 45(1):81-94.
• [31]Furey TS: ChIP-seq and beyond: new and improved methodologies to detect and characterize protein-DNA interactions. Nat Rev Genet 2012, 13(12):840-852.
• [32]Myers EW, Sutton GG, Delcher AL, Dew IM, Fasulo DP, Flanigan MJ, Kravitz SA, Mobarry CM, Reinert KH, Remington KA, et al.: A whole-genome assembly of drosophila. Science 2000, 287(5461):2196-2204.
• [33]Havlak P, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Weinstock GM, Gibbs RA: The atlas genome assembly system. Genome Res 2004, 14(4):721-732.
• [34]Batzoglou S, Jaffe DB, Stanley K, Butler J, Gnerre S, Mauceli E, Berger B, Mesirov JP, Lander ES: ARACHNE: a whole-genome shotgun assembler. Genome Res 2002, 12(1):177-189.
• [35]Aparicio S, Chapman J, Stupka E, Putnam N, Chia JM, Dehal P, Christoffels A, Rash S, Hoon S, Smit A, et al.: Whole-genome shotgun assembly and analysis of the genome of fugu rubripes. Science 2002, 297(5585):1301-1310.
• [36]Huang X, Wang J, Aluru S, Yang SP, Hillier L: PCAP: a whole-genome assembly program. Genome Res 2003, 13(9):2164-2170.
• [37]Simpson JT, Wong K, Jackman SD, Schein JE, Jones SJ, Birol I: ABySS: a parallel assembler for short read sequence data. Genome Res 2009, 19(6):1117-1123.
• [38]Zerbino DR, Birney E: Velvet: algorithms for de novo short read assembly using de bruijn graphs. Genome Res 2008, 18(5):821-829.
• [39]Mullikin JC, Ning Z: The phusion assembler. Genome Res 2003, 13(1):81-90.
• [40]Wheeler DL, Barrett T, Benson DA, Bryant SH, Canese K, Chetvernin V, Church DM, DiCuccio M, Edgar R, Federhen S, et al.: Database resources of the national center for biotechnology information. Nucleic Acids Res 2007, 35(Database issue):D5-12.
• [41]Stenson PD, Ball EV, Mort M, Phillips AD, Shaw K, Cooper DN: The human gene mutation database (HGMD) and its exploitation in the fields of personalized genomics and molecular evolution. In Current protocols in bioinformatics Edited by Baxevanis AD. 2012. Chapter 1:Unit1 13. PMID:22948725
• [42]Brookes AJ, Lehvaslaiho H, Siegfried M, Boehm JG, Yuan YP, Sarkar CM, Bork P, Ortigao F: HGBASE: a database of SNPs and other variations in and around human genes. Nucleic Acids Res 2000, 28(1):356-360.
• [43]Fredman D, Siegfried M, Yuan YP, Bork P, Lehvaslaiho H, Brookes AJ: HGVbase: a human sequence variation database emphasizing data quality and a broad spectrum of data sources. Nucleic Acids Res 2002, 30(1):387-391.
• [44]The GWAS central. http://www.gwascentral.org webcite
• [45]The SNPedia. http://www.snpedia.com/index.php/SNPedia webcite
• [46]Karchin R: Next generation tools for the annotation of human SNPs. Brief Bioinform 2009, 10(1):35-52.
• [47]Medvedev P, Stanciu M, Brudno M: Computational methods for discovering structural variation with next-generation sequencing. Nat Methods 2009, 6(11 Suppl):S13-20.
• [48]Cock PJ, Fields CJ, Goto N, Heuer ML, Rice PM: The sanger FASTQ file format for sequences with quality scores, and the solexa/illumina FASTQ variants. Nucleic Acids Res 2010, 38(6):1767-1771.
• [49]Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R: Genome project data processing S: the sequence alignment/Map format and SAMtools. Bioinformatics 2009, 25(16):2078-2079.
• [50]Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, Handsaker RE, Lunter G, Marth GT, Sherry ST, et al.: The variant call format and VCFtools. Bioinformatics 2011, 27(15):2156-2158.
• [51]Ewing B, Hillier L, Wendl MC, Green P: Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res 1998, 8(3):175-185.
• [52]Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ, Greenman CD, Varela I, Lin ML, Ordonez GR, Bignell GR, et al.: A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 2010, 463(7278):191-196.
• [53]Deorowicz S, Grabowski S: Compression of genomic sequences in FASTQ format. Bioinformatics 2011. PMID: 21252073
• [54]Tembe W, Lowey J, Suh E: G-SQZ: compact encoding of genomic sequence and quality data. Bioinformatics 2010, 26(17):2192-2194.
• [55]Cock PJ, Antao T, Chang JT, Chapman BA, Cox CJ, Dalke A, Friedberg I, Hamelryck T, Kauff F, Wilczynski B, et al.: Biopython: freely available python tools for computational molecular biology and bioinformatics. Bioinformatics 2009, 25(11):1422-1423.
• [56]Stajich JE, Block D, Boulez K, Brenner SE, Chervitz SA, Dagdigian C, Fuellen G, Gilbert JG, Korf I, Lapp H, et al.: The bioperl toolkit: perl modules for the life sciences. Genome Res 2002, 12(10):1611-1618.
• [57]Goto N, Prins P, Nakao M, Bonnal R, Aerts J, Katayama T: BioRuby: bioinformatics software for the ruby programming language. Bioinformatics 2010, 26(20):2617-2619.
• [58]Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R: The sequence alignment/Map format and SAMtools. Bioinformatics 2009, 25(16):2078-2079.
• [59]Botstein D, Risch N: Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease. Nat Genet 2003, 33(Suppl):228-237.
• [60]Altshuler D, Daly MJ, Lander ES: Genetic mapping in human disease. Science 2008, 322(5903):881-888.
• [61]Chen K, Wallis JW, McLellan MD, Larson DE, Kalicki JM, Pohl CS, McGrath SD, Wendl MC, Zhang Q, Locke DP, et al.: BreakDancer: an algorithm for high-resolution mapping of genomic structural variation. Nat Methods 2009, 6(9):677-681.
• [62]Xie C, Tammi MT: CNV-seq, a new method to detect copy number variation using high-throughput sequencing. BMC Bioinforma 2009, 10:80. BioMed Central Full Text
• [63]Sindi S, Helman E, Bashir A, Raphael BJ: A geometric approach for classification and comparison of structural variants. Bioinformatics 2009, 25(12):i222-230.
• [64]Quinlan AR, Clark RA, Sokolova S, Leibowitz ML, Zhang Y, Hurles ME, Mell JC, Hall IM: Genome-wide mapping and assembly of structural variant breakpoints in the mouse genome. Genome Res 2010, 20(5):623-635.
• [65]Lee S, Hormozdiari F, Alkan C, Brudno M: MoDIL: detecting small indels from clone-end sequencing with mixtures of distributions. Nat Methods 2009, 6(7):473-474.
• [66]Hach F, Hormozdiari F, Alkan C, Hormozdiari F, Birol I, Eichler EE, Sahinalp SC: mrsFAST: a cache-oblivious algorithm for short-read mapping. Nat Methods 2010, 7(8):576-577.
• [67]Hajirasouliha I, Hormozdiari F, Alkan C, Kidd JM, Birol I, Eichler EE, Sahinalp SC: Detection and characterization of novel sequence insertions using paired-end next-generation sequencing. Bioinformatics 2010, 26(10):1277-1283.
• [68]Korbel JO, Abyzov A, Mu XJ, Carriero N, Cayting P, Zhang Z, Snyder M, Gerstein MB: PEMer: a computational framework with simulation-based error models for inferring genomic structural variants from massive paired-end sequencing data. Genome Biol 2009, 10(2):R23. BioMed Central Full Text
• [69]Ye K, Schulz MH, Long Q, Apweiler R, Ning Z: Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics 2009, 25(21):2865-2871.
• [70]Kim TM, Luquette LJ, Xi R, Park PJ: rSW-seq: algorithm for detection of copy number alterations in deep sequencing data. BMC Bioinforma 2010, 11:432. BioMed Central Full Text
• [71]Hormozdiari F, Hajirasouliha I, Dao P, Hach F, Yorukoglu D, Alkan C, Eichler EE, Sahinalp SC: Next-generation VariationHunter: combinatorial algorithms for transposon insertion discovery. Bioinformatics 2010, 26(12):i350-357.
• [72]Koboldt DC, Zhang Q, Larson DE, Shen D, McLellan MD, Lin L, Miller CA, Mardis ER, Ding L, Wilson RK: VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res 2012, 22(3):568-576.
• [73]Koboldt DC, Chen K, Wylie T, Larson DE, McLellan MD, Mardis ER, Weinstock GM, Wilson RK, Ding L: VarScan: variant detection in massively parallel sequencing of individual and pooled samples. Bioinformatics 2009, 25(17):2283-2285.
• [74]McClellan J, King MC: Genetic heterogeneity in human disease. Cell 2010, 141(2):210-217.
• [75]Cantor RM, Lange K, Sinsheimer JS: Prioritizing GWAS results: a review of statistical methods and recommendations for their application. Am J Hum Genet 2010, 86(1):6-22.
• [76]Sifrim A, Van Houdt JK, Tranchevent LC, Nowakowska B, Sakai R, Pavlopoulos GA, Devriendt K, Vermeesch JR, Moreau Y, Aerts J: Annotate-it: a swiss-knife approach to annotation, analysis and interpretation of single nucleotide variation in human disease. Genome Med 2012, 4(9):73. BioMed Central Full Text
• [77]Li MX, Gui HS, Kwan JS, Bao SY, Sham PC: A comprehensive framework for prioritizing variants in exome sequencing studies of mendelian diseases. Nucleic Acids Res 2012, 40(7):e53.
• [78]Wang K, Li M, Hakonarson H: ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010, 38(16):e164.
• [79]Makarov V, O'Grady T, Cai G, Lihm J, Buxbaum JD, Yoon S: AnnTools: a comprehensive and versatile annotation toolkit for genomic variants. Bioinformatics 2012, 28(5):724-725.
• [80]Shetty AC, Athri P, Mondal K, Horner VL, Steinberg KM, Patel V, Caspary T, Cutler DJ, Zwick ME: SeqAnt: a web service to rapidly identify and annotate DNA sequence variations. BMC Bioinforma 2010, 11:471. BioMed Central Full Text
• [81]Ge D, Ruzzo EK, Shianna KV, He M, Pelak K, Heinzen EL, Need AC, Cirulli ET, Maia JM, Dickson SP, et al.: SVA: software for annotating and visualizing sequenced human genomes. Bioinformatics 2011, 27(14):1998-2000.
• [82]Asmann YW, Middha S, Hossain A, Baheti S, Li Y, Chai HS, Sun Z, Duffy PH, Hadad AA, Nair A, et al.: TREAT: a bioinformatics tool for variant annotations and visualizations in targeted and exome sequencing data. Bioinformatics 2012, 28(2):277-278.
• [83]Yandell M, Huff C, Hu H, Singleton M, Moore B, Xing J, Jorde LB, Reese MG: A probabilistic disease-gene finder for personal genomes. Genome Res 2011, 21(9):1529-1542.
• [84]Cheng YC, Hsiao FC, Yeh EC, Lin WJ, Tang CY, Tseng HC, Wu HT, Liu CK, Chen CC, Chen YT, et al.: VarioWatch: providing large-scale and comprehensive annotations on human genomic variants in the next generation sequencing era. Nucleic Acids Res 2012, 40(Web Server issue):W76-81.
• [85]Sincan M, Simeonov DR, Adams D, Markello TC, Pierson TM, Toro C, Gahl WA, Boerkoel CF: VAR-MD: a tool to analyze whole exome-genome variants in small human pedigrees with mendelian inheritance. Hum Mutat 2012, 33(4):593-598.
• [86]Teer JK, Green ED, Mullikin JC, Biesecker LG: VarSifter: visualizing and analyzing exome-scale sequence variation data on a desktop computer. Bioinformatics 2012, 28(4):599-600.
• [87]O'Donoghue SI, Gavin AC, Gehlenborg N, Goodsell DS, Heriche JK, Nielsen CB, North C, Olson AJ, Procter JB, Shattuck DW, et al.: Visualizing biological data-now and in the future. Nat Methods 2010, 7(3 Suppl):S2-4.
• [88]Nielsen CB, Jackman SD, Birol I, Jones SJ: ABySS-explorer: visualizing genome sequence assemblies. IEEE Trans Vis Comput Graph 2009, 15(6):881-888.
• [89]Huang W, Marth G: EagleView: a genome assembly viewer for next-generation sequencing technologies. Genome Res 2008, 18(9):1538-1543.
• [90]Schatz MC, Phillippy AM, Sommer DD, Delcher AL, Puiu D, Narzisi G, Salzberg SL, Pop M: Hawkeye and AMOS: visualizing and assessing the quality of genome assemblies. Brief Bioinform 2013, 14(2):213-224.
• [91]Manske HM, Kwiatkowski DP: LookSeq: a browser-based viewer for deep sequencing data. Genome Res 2009, 19(11):2125-2132.
• [92]Hou H, Zhao F, Zhou L, Zhu E, Teng H, Li X, Bao Q, Wu J, Sun Z: MagicViewer: integrated solution for next-generation sequencing data visualization and genetic variation detection and annotation. Nucleic Acids Res 2010, 38(Web Server issue):W732-736.
• [93]Bao H, Guo H, Wang J, Zhou R, Lu X, Shi S: MapView: visualization of short reads alignment on a desktop computer. Bioinformatics 2009, 25(12):1554-1555.
• [94]Furey TS: Comparison of human (and other) genome browsers. Hum Genomics 2006, 2(4):266-270. BioMed Central Full Text
• [95]Cline MS, Kent WJ: Understanding genome browsing. Nat Biotechnol 2009, 27(2):153-155.
• [96]Nielsen CB, Cantor M, Dubchak I, Gordon D, Wang T: Visualizing genomes: techniques and challenges. Nat Methods 2010, 7(3 Suppl):S5-S15.
• [97]AnnoJ. http://www.annoj.org webcite
• [98]Grant JR, Stothard P: The CGView server: a comparative genomics tool for circular genomes. Nucleic Acids Res 2008, 36(Web Server issue):W181-184.
• [99]Engels R, Yu T, Burge C, Mesirov JP, DeCaprio D, Galagan JE: Combo: a whole genome comparative browser. Bioinformatics 2006, 22(14):1782-1783.
• [100]Flicek P, Amode MR, Barrell D, Beal K, Brent S, Carvalho-Silva D, Clapham P, Coates G, Fairley S, Fitzgerald S, et al.: Ensembl 2012. Nucleic Acids Res 2012, 40(Database issue):D84-90.
• [101]Hubbard T, Barker D, Birney E, Cameron G, Chen Y, Clark L, Cox T, Cuff J, Curwen V, Down T, et al.: The ensembl genome database project. Nucleic Acids Res 2002, 30(1):38-41.
• [102]Papanicolaou A, Heckel DG: The GMOD drupal bioinformatic server framework. Bioinformatics 2010, 26(24):3119-3124.
• [103]Wang H, Su Y, Mackey AJ, Kraemer ET, Kissinger JC: SynView: a GBrowse-compatible approach to visualizing comparative genome data. Bioinformatics 2006, 22(18):2308-2309.
• [104]Stein LD, Mungall C, Shu S, Caudy M, Mangone M, Day A, Nickerson E, Stajich JE, Harris TW, Arva A, et al.: The generic genome browser: a building block for a model organism system database. Genome Res 2002, 12(10):1599-1610.
• [105]Arakawa K, Tamaki S, Kono N, Kido N, Ikegami K, Ogawa R, Tomita M: Genome projector: zoomable genome map with multiple views. BMC Bioinforma 2009, 10:31. BioMed Central Full Text
• [106]Nicol JW, Helt GA, Blanchard SG Jr, Raja A, Loraine AE: The integrated genome browser: free software for distribution and exploration of genome-scale datasets. Bioinformatics 2009, 25(20):2730-2731.
• [107]Thorvaldsdottir H, Robinson JT, Mesirov JP: Integrative genomics viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform 2013, 14(2):178-192.
• [108]Zhu J, Sanborn JZ, Benz S, Szeto C, Hsu F, Kuhn RM, Karolchik D, Archie J, Lenburg ME, Esserman LJ, et al.: The UCSC cancer genomics browser. Nat Methods 2009, 6(4):239-240.
• [109]Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D: The human genome browser at UCSC. Genome Res 2002, 12(6):996-1006.
• [110]Yates T, Okoniewski MJ, Miller CJ: X:Map: annotation and visualization of genome structure for affymetrix exon array analysis. Nucleic Acids Res 2008, 36(Database issue):D780-786.
• [111]Sinha AU, Meller J: Cinteny: flexible analysis and visualization of synteny and genome rearrangements in multiple organisms. BMC Bioinforma 2007, 8:82. BioMed Central Full Text
• [112]Yin T, Cook D, Lawrence M: Ggbio: an R package for extending the grammar of graphics for genomic data. Genome Biol 2012, 13(8):R77. BioMed Central Full Text
• [113]Yang J, Wang J, Yao ZJ, Jin Q, Shen Y, Chen R: GenomeComp: a visualization tool for microbial genome comparison. J Microbiol Methods 2003, 54(3):423-426.
• [114]Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D, Jones SJ, Marra MA: Circos: an information aesthetic for comparative genomics. Genome Res 2009, 19(9):1639-1645.
• [115]Deng X, Rayner S, Liu X, Zhang Q, Yang Y, Li N: DHPC: a new tool to express genome structural features. Genomics 2008, 91(5):476-483.
• [116]Anders S: Visualization of genomic data with the hilbert curve. Bioinformatics 2009, 25(10):1231-1235. PMID: 23605045
• [117]Qi J, Zhao F: InGAP-sv: a novel scheme to identify and visualize structural variation from paired end mapping data. Nucleic Acids Res 2011, 39(Web Server issue):W567-575.
• [118]Pavlopoulos GA, Kumar P, Sifrim A, Sakai R, Lin ML, Voet T, Moreau Y, Aerts J: Meander: visually exploring the structural variome using space-filling curves. Nucleic Acids Res 2013.
• [119]MEDEA: Comparative genomic visualization with adobe flash. [http://www.broadinstitute.org/annotation/medea/ webcite]
• [120]Meyer M, Munzner T, Pfister H: MizBee: a multiscale synteny browser. IEEE Trans Vis Comput Graph 2009, 15(6):897-904.
• [121]Esteban-Marcos A, Darling AE, Ragan MA: Seevolution: visualizing chromosome evolution. Bioinformatics 2009, 25(7):960-961.
• [122]Crabtree J, Angiuoli SV, Wortman JR, White OR: Sybil: methods and software for multiple genome comparison and visualization. Methods Mol Biol 2007, 408:93-108. Clifton, NJ
• [123]Mayor C, Brudno M, Schwartz JR, Poliakov A, Rubin EM, Frazer KA, Pachter LS, Dubchak I: VISTA : visualizing global DNA sequence alignments of arbitrary length. Bioinformatics 2000, 16(11):1046-1047.
• [124]Pavlopoulos GA, Soldatos TG, Barbosa-Silva A, Schneider R: A reference guide for tree analysis and visualization. BioData Min 2010, 3(1):1. BioMed Central Full Text
• [125]Pavlopoulos GA, Wegener AL, Schneider R: A survey of visualization tools for biological network analysis. BioData Min 2008, 1:12. BioMed Central Full Text