Genome-Wide Mapping of Copy Number Variation in Humans: Comparative Analysis of High Resolution Array Platforms
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{"title"=>"Genome-wide mapping of copy number variation in humans: Comparative analysis of high resolution array platforms", "type"=>"journal", "authors"=>[{"first_name"=>"Rajini R.", "last_name"=>"Haraksingh", "scopus_author_id"=>"36607998200"}, {"first_name"=>"Alexej", "last_name"=>"Abyzov", "scopus_author_id"=>"8732206000"}, {"first_name"=>"Mark", "last_name"=>"Gerstein", "scopus_author_id"=>"24755400900"}, {"first_name"=>"Alexander E.", "last_name"=>"Urban", "scopus_author_id"=>"7103271580"}, {"first_name"=>"Michael", "last_name"=>"Snyder", "scopus_author_id"=>"35355673100"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"363007815", "sgr"=>"82355181986", "issn"=>"19326203", "pmid"=>"22140474", "scopus"=>"2-s2.0-82355181986", "doi"=>"10.1371/journal.pone.0027859", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"35144a4d-a371-38b3-ae42-d4055ad6b97a", "abstract"=>"Accurate and efficient genome-wide detection of copy number variants (CNVs) is essential for understanding human genomic variation, genome-wide CNV association type studies, cytogenetics research and diagnostics, and independent validation of CNVs identified from sequencing based technologies. Numerous, array-based platforms for CNV detection exist utilizing array Comparative Genome Hybridization (aCGH), Single Nucleotide Polymorphism (SNP) genotyping or both. We have quantitatively assessed the abilities of twelve leading genome-wide CNV detection platforms to accurately detect Gold Standard sets of CNVs in the genome of HapMap CEU sample NA12878, and found significant differences in performance. The technologies analyzed were the NimbleGen 4.2 M, 2.1 M and 3×720 K Whole Genome and CNV focused arrays, the Agilent 1×1 M CGH and High Resolution and 2×400 K CNV and SNP+CGH arrays, the Illumina Human Omni1Quad array and the Affymetrix SNP 6.0 array. The Gold Standards used were a 1000 Genomes Project sequencing-based set of 3997 validated CNVs and an ultra high-resolution aCGH-based set of 756 validated CNVs. We found that sensitivity, total number, size range and breakpoint resolution of CNV calls were highest for CNV focused arrays. Our results are important for cost effective CNV detection and validation for both basic and clinical applications.", "link"=>"http://www.mendeley.com/research/genomewide-mapping-copy-number-variation-humans-comparative-analysis-high-resolution-array-platforms-1", "reader_count"=>118, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>6, "Librarian"=>1, "Student > Doctoral Student"=>7, "Researcher"=>33, "Student > Ph. D. Student"=>36, "Student > Postgraduate"=>7, "Other"=>4, "Student > Master"=>9, "Student > Bachelor"=>9, "Lecturer > Senior Lecturer"=>4, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>6, "Librarian"=>1, "Student > Doctoral Student"=>7, "Researcher"=>33, "Student > Ph. D. Student"=>36, "Student > Postgraduate"=>7, "Other"=>4, "Student > Master"=>9, "Student > Bachelor"=>9, "Lecturer > Senior Lecturer"=>4, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>14, "Mathematics"=>2, "Agricultural and Biological Sciences"=>77, "Medicine and Dentistry"=>10, "Physics and Astronomy"=>1, "Chemistry"=>2, "Psychology"=>1, "Social Sciences"=>1, "Computer Science"=>6, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Chemistry"=>{"Chemistry"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>77}, "Computer Science"=>{"Computer Science"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>14}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Hong Kong"=>2, "United States"=>4, "Uruguay"=>1, "United Kingdom"=>2, "Thailand"=>1, "Canada"=>1, "Netherlands"=>1, "Korea (South)"=>1, "Belgium"=>1, "Norway"=>1, "China"=>1, "Poland"=>1, "Denmark"=>1, "France"=>1, "Germany"=>1}, "group_count"=>6}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/708488"], "description"=>"<p>Each data point represents the number of platforms that detect a certain Gold Standard CNV by at least one technical replicate using our overlap criteria versus the size of the Gold Standard CNV. Only detectable Gold Standard CNVs are shown. Blue points correspond to 1000GP GS CNVs and pink points correspond to 42 M GS CNVs.</p>", "links"=>[], "tags"=>["platforms", "detecting", "cnv"], "article_id"=>378848, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Rajini R. Haraksingh", "Alexej Abyzov", "Mark Gerstein", "Alexander E. Urban", "Michael Snyder"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027859.g006", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_array_platforms_detecting_each_Gold_Standard_CNV_by_size_/378848", "title"=>"Number of array platforms detecting each Gold Standard CNV by size.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-30 02:27:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/708554"], "description"=>"<p>Copy Number Variants in one genome can only be defined with respect to a reference genome. Comparisons to different reference genomes will produce different sets of CNVs for the same test genome. Sequencing based methods directly compare the test genome to the reference genome. For array-based methods however, this comparison is indirect as an experimental control genome is also required. The relationship between the reference genome and this control genome determines which CNVs in the test sample (with respect to the reference genome) are detected.</p>", "links"=>[], "tags"=>["relationships", "genomes", "resulting", "abilities", "methods", "cnvs", "genome"], "article_id"=>378911, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Rajini R. Haraksingh", "Alexej Abyzov", "Mark Gerstein", "Alexander E. Urban", "Michael Snyder"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027859.t002", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_possible_relationships_between_reference_experimental_control_and_test_genomes_and_the_resulting_abilities_of_different_methods_to_detect_CNVs_in_the_test_genome_with_respect_to_the_reference_genome_/378911", "title"=>"Summary of possible relationships between reference, experimental control and test genomes and the resulting abilities of different methods to detect CNVs in the test genome (with respect to the reference genome).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-11-30 02:28:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/708310"], "description"=>"<p>Depicted are the average corrected platform sensitivities based on two technical replicates for each platform, except the Affymetrix SNP 6.0. Corrected sensitivities were calculated using only those Gold Standard CNVs that were detectable by at least one platform. Blue bars show sensitivity to the detectable 1000GP GS and pink bars show sensitivity to the detectable 42 M GS.</p>", "links"=>[], "tags"=>["sensitivities", "detecting"], "article_id"=>378670, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Rajini R. Haraksingh", "Alexej Abyzov", "Mark Gerstein", "Alexander E. Urban", "Michael Snyder"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027859.g004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Array_sensitivities_to_detecting_Gold_Standard_CNVs_/378670", "title"=>"Array sensitivities to detecting Gold Standard CNVs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-30 02:24:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/708212"], "description"=>"<p>Each data point plots the size of a platform CNV versus the size of the corresponding Gold Standard CNV that individually overlaps the platform call by 50% reciprocally. Events overlapping the 1000GP GS CNVs are shown in blue. Events overlapping the 42 M GS CNVs are shown in pink. Total numbers of data points and R<sup>2</sup> values are indicated in the table below. Data is an aggregate of all events from two technical replicates for each platform except the Affymetrix SNP 6.0. The size distribution and total number of platform CNVs that overlap Gold Standard CNVs in this way are also clearly visible.</p>", "links"=>[], "tags"=>["cnv", "calls"], "article_id"=>378571, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Rajini R. Haraksingh", "Alexej Abyzov", "Mark Gerstein", "Alexander E. Urban", "Michael Snyder"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027859.g003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Resolution_of_array_platform_CNV_calls_for_known_Gold_Standard_CNVs_/378571", "title"=>"Resolution of array platform CNV calls for known Gold Standard CNVs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-30 02:22:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/359940", "https://ndownloader.figshare.com/files/359985", "https://ndownloader.figshare.com/files/360033"], "description"=>"<div><p>Accurate and efficient genome-wide detection of copy number variants (CNVs) is essential for understanding human genomic variation, genome-wide CNV association type studies, cytogenetics research and diagnostics, and independent validation of CNVs identified from sequencing based technologies. Numerous, array-based platforms for CNV detection exist utilizing array Comparative Genome Hybridization (aCGH), Single Nucleotide Polymorphism (SNP) genotyping or both. We have quantitatively assessed the abilities of twelve leading genome-wide CNV detection platforms to accurately detect Gold Standard sets of CNVs in the genome of HapMap CEU sample NA12878, and found significant differences in performance. The technologies analyzed were the NimbleGen 4.2 M, 2.1 M and 3×720 K Whole Genome and CNV focused arrays, the Agilent 1×1 M CGH and High Resolution and 2×400 K CNV and SNP+CGH arrays, the Illumina Human Omni1Quad array and the Affymetrix SNP 6.0 array. The Gold Standards used were a 1000 Genomes Project sequencing-based set of 3997 validated CNVs and an ultra high-resolution aCGH-based set of 756 validated CNVs. We found that sensitivity, total number, size range and breakpoint resolution of CNV calls were highest for CNV focused arrays. Our results are important for cost effective CNV detection and validation for both basic and clinical applications.</p> </div>", "links"=>[], "tags"=>["genome-wide", "comparative", "platforms"], "article_id"=>131135, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Rajini R. Haraksingh", "Alexej Abyzov", "Mark Gerstein", "Alexander E. Urban", "Michael Snyder"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0027859.s001", "https://dx.doi.org/10.1371/journal.pone.0027859.s002", "https://dx.doi.org/10.1371/journal.pone.0027859.s003"], "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genome_Wide_Mapping_of_Copy_Number_Variation_in_Humans_Comparative_Analysis_of_High_Resolution_Array_Platforms/131135", "title"=>"Genome-Wide Mapping of Copy Number Variation in Humans: Comparative Analysis of High Resolution Array Platforms", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-11-30 00:18:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/708066"], "description"=>"<p>Depicted are the log<sub>2</sub> ratios of NA12878 to the control genome and locations along the chromosome for each probe (blue dot) in this region. Gene, 1000 Genomes Project Gold Standard CNVs (1000GP CNVs) and Segmental Duplication (SD) tracks are shown. The CNV highlighted in the red box was called by both replicates for all twelve platforms using the manufacturer-recommended software and parameters. Red arrows indicate examples of additional array-specific CNV calls. A. NimbleGen 4.2 M Whole Genome, B. NimbleGen 4.2 M CNV, C. NimbleGen 2.1 M Whole Genome, D. NimbleGen 2.1 M CNV, E. NimbleGen 3×720 K Whole Genome, F. NimbleGen 3×720 K CNV, G. Agilent 1×1 M CGH, H. Agilent 1×1 M High Resolution, I. Agilent 2×400 K CNV, J. Agilent 2×400 K CGH+SNP, K. Illumina Human Omni1Quad, L. Affymetrix SNP 6.0.</p>", "links"=>[], "tags"=>["57", "kb", "cnv", "chromosome", "1q44"], "article_id"=>378419, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Rajini R. Haraksingh", "Alexej Abyzov", "Mark Gerstein", "Alexander E. Urban", "Michael Snyder"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027859.g001", "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Detection_of_a_known_57_kb_CNV_on_chromosome_1q44_by_twelve_different_array_platforms_/378419", "title"=>"Detection of a known 57 kb CNV on chromosome 1q44 by twelve different array platforms.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-30 02:20:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/708591"], "description"=>"<p>Summary of CNV detection platforms and experiments.</p>", "links"=>[], "tags"=>["cnv", "detection", "platforms"], "article_id"=>378948, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Rajini R. Haraksingh", "Alexej Abyzov", "Mark Gerstein", "Alexander E. Urban", "Michael Snyder"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027859.t001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_CNV_detection_platforms_and_experiments_/378948", "title"=>"Summary of CNV detection platforms and experiments.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-11-30 02:29:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/708135"], "description"=>"<p>Data include CNVs from all replicates of the fourteen different experiments listed in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027859#pone-0027859-t001\" target=\"_blank\">table 1</a> (twelve different platforms and two different conditions for NimbleGen 2.1 M arrays). The size distributions of the two Gold Standards are overlaid for reference. The apparent frequency spikes are results of the changing bin size.</p>", "links"=>[], "tags"=>["distributions", "cnv"], "article_id"=>378497, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Rajini R. Haraksingh", "Alexej Abyzov", "Mark Gerstein", "Alexander E. Urban", "Michael Snyder"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027859.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Size_distributions_of_CNV_call_sets_/378497", "title"=>"Size distributions of CNV call sets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-30 02:21:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/708387"], "description"=>"<p>(a) Venn diagram showing overlap of CNV calls from a single platform (NimbleGen 2.1 M CNV) with the detectable 1000 Genomes Gold Standard. (b) The percentage of Gold Standard CNVs that were detected by at least one technical replicate of each platform is shown for all platforms (including twelve different platforms and two conditions for the NimbleGen 2.1 M arrays). Blue bars indicated percentage of 1000GP GS CNVs and pink bars indicate percentage of 42 M GS CNVs. (c) Platform distribution of all Gold Standard CNVs that are detected by only one platform.</p>", "links"=>[], "tags"=>["detectable"], "article_id"=>378751, "categories"=>["Biological Sciences", "Genetics"], "users"=>["Rajini R. Haraksingh", "Alexej Abyzov", "Mark Gerstein", "Alexander E. Urban", "Michael Snyder"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027859.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Array_detectable_Gold_Standard_CNVs_/378751", "title"=>"Array detectable Gold Standard CNVs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-30 02:25:51"}

PMC Usage Stats | Further Information

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Relative Metric

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