DeepSAGE Reveals Genetic Variants Associated with Alternative Polyadenylation and Expression of Coding and Non-coding Transcripts
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{"title"=>"DeepSAGE Reveals Genetic Variants Associated with Alternative Polyadenylation and Expression of Coding and Non-coding Transcripts", "type"=>"journal", "authors"=>[{"first_name"=>"Daria V.", "last_name"=>"Zhernakova", "scopus_author_id"=>"57196003566"}, {"first_name"=>"Eleonora", "last_name"=>"de Klerk", "scopus_author_id"=>"55391175200"}, {"first_name"=>"Harm Jan", "last_name"=>"Westra", "scopus_author_id"=>"57194920285"}, {"first_name"=>"Anastasios", "last_name"=>"Mastrokolias", "scopus_author_id"=>"54896405200"}, {"first_name"=>"Shoaib", "last_name"=>"Amini", "scopus_author_id"=>"55780784800"}, {"first_name"=>"Yavuz", "last_name"=>"Ariyurek", "scopus_author_id"=>"6507445299"}, {"first_name"=>"Rick", "last_name"=>"Jansen", "scopus_author_id"=>"56596168300"}, {"first_name"=>"Brenda W.", "last_name"=>"Penninx", "scopus_author_id"=>"55800249300"}, {"first_name"=>"Jouke J.", "last_name"=>"Hottenga", "scopus_author_id"=>"6508277910"}, {"first_name"=>"Gonneke", "last_name"=>"Willemsen", "scopus_author_id"=>"6701522277"}, {"first_name"=>"Eco J.", "last_name"=>"de Geus", "scopus_author_id"=>"7006594888"}, {"first_name"=>"Dorret I.", "last_name"=>"Boomsma", "scopus_author_id"=>"35378012400"}, {"first_name"=>"Jan H.", "last_name"=>"Veldink", "scopus_author_id"=>"6603240539"}, {"first_name"=>"Leonard H.", "last_name"=>"van den Berg", "scopus_author_id"=>"7101946205"}, {"first_name"=>"Cisca", "last_name"=>"Wijmenga", "scopus_author_id"=>"7005273061"}, {"first_name"=>"Johan T.", "last_name"=>"den Dunnen", "scopus_author_id"=>"55599147900"}, {"first_name"=>"Gert Jan B.", "last_name"=>"van Ommen", "scopus_author_id"=>"35411955100"}, {"first_name"=>"Peter A.C.", "last_name"=>"'t Hoen", "scopus_author_id"=>"55909479400"}, {"first_name"=>"Lude", "last_name"=>"Franke", "scopus_author_id"=>"56310093600"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"23818875", "sgr"=>"84879674031", "doi"=>"10.1371/journal.pgen.1003594", "scopus"=>"2-s2.0-84879674031", "pui"=>"369235369", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "issn"=>"15537390"}, "id"=>"306415a8-32e5-3a16-901b-a0b290864937", "abstract"=>"Many disease-associated variants affect gene expression levels (expression quantitative trait loci, eQTLs) and expression profiling using next generation sequencing (NGS) technology is a powerful way to detect these eQTLs. We analyzed 94 total blood samples from healthy volunteers with DeepSAGE to gain specific insight into how genetic variants affect the expression of genes and lengths of 3'-untranslated regions (3'-UTRs). We detected previously unknown cis-eQTL effects for GWAS hits in disease- and physiology-associated traits. Apart from cis-eQTLs that are typically easily identifiable using microarrays or RNA-sequencing, DeepSAGE also revealed many cis-eQTLs for antisense and other non-coding transcripts, often in genomic regions containing retrotransposon-derived elements. We also identified and confirmed SNPs that affect the usage of alternative polyadenylation sites, thereby potentially influencing the stability of messenger RNAs (mRNA). We then combined the power of RNA-sequencing with DeepSAGE by performing a meta-analysis of three datasets, leading to the identification of many more cis-eQTLs. Our results indicate that DeepSAGE data is useful for eQTL mapping of known and unknown transcripts, and for identifying SNPs that affect alternative polyadenylation. Because of the inherent differences between DeepSAGE and RNA-sequencing, our complementary, integrative approach leads to greater insight into the molecular consequences of many disease-associated variants.", "link"=>"http://www.mendeley.com/research/deepsage-reveals-genetic-variants-associated-alternative-polyadenylation-expression-coding-noncoding", "reader_count"=>90, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>6, "Student > Doctoral Student"=>4, "Researcher"=>22, "Student > Ph. D. Student"=>32, "Student > Postgraduate"=>2, "Student > Master"=>10, "Other"=>1, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>6, "Student > Doctoral Student"=>4, "Researcher"=>22, "Student > Ph. D. Student"=>32, "Student > Postgraduate"=>2, "Student > Master"=>10, "Other"=>1, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>17, "Agricultural and Biological Sciences"=>56, "Medicine and Dentistry"=>8, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>1, "Psychology"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>56}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>17}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Netherlands"=>2, "Belgium"=>1, "United States"=>1, "China"=>1, "Brazil"=>1, "Denmark"=>1, "Italy"=>1, "United Kingdom"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1095783"], "description"=>"<p>The ratio between the abundance of transcripts with proximal and distal 3′-UTR RT-qPCR products in <i>IRF5</i> (left) and <i>HPS1</i> (right) depends on the genotypes of <i>cis-</i>regulating SNPs rs10488630 and rs11189600, respectively. N denotes the number of individuals included in the analysis. These results indicate allele-specific preference for use of a proximal and distal polyadenlyation site.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "polyadenylation", "genes", "depends", "genotypes", "rs10488630"], "article_id"=>727244, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.g005", "stats"=>{"downloads"=>5, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_choice_of_proximal_distal_polyadenylation_site_in_genes_IRF5_and_HPS1_depends_on_the_genotypes_of_rs10488630_and_rs11189600_respectively_/727244", "title"=>"The choice of proximal/distal polyadenylation site in genes <i>IRF5</i> and <i>HPS1</i> depends on the genotypes of rs10488630 and rs11189600, respectively.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-20 02:00:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095780"], "description"=>"<p>For each dataset, all genes were sorted by their mean gene expression levels, and divided into ten equal bins. The X-axis reflects these bins, which are sorted by increasing mean gene expression levels. The Y-axis reflects the fraction of <i>cis</i>-regulated genes that fall into each bin.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "genes", "bins", "deepsage", "affymetrix"], "article_id"=>727241, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.g002", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fraction_of_cis_regulated_genes_in_bins_by_mean_gene_expression_levels_for_DeepSAGE_and_Affymetrix_data_/727241", "title"=>"Fraction of <i>cis-</i>regulated genes in bins by mean gene expression levels for DeepSAGE and Affymetrix data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-20 02:00:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095778"], "description"=>"<p>A) DeepSAGE data preparation consists of the following basic steps: after RNA extraction the polyadenylated mRNA fraction is captured with oligo-dT beads. While RNA is still bound to the beads, double-stranded cDNA synthesis is performed. Next, cDNA is digested by NlaIII restriction enzyme (an anchoring enzyme), which cuts the DNA at CATG recognition sequences, leaving only the fragment with the most distal (3′) CATG site associated with the beads. Subsequently, a GEX adapter is attached to the 5′ end. This adapter contains a recognition sequence for the MmeI restriction enzyme that cuts the sequence 17 bp downstream of CATG site. After ligation of a second GEX adapter, fragments containing 21 bp tags (17 unknown nucleotides + CATG) are ready for sequencing. B) A typical protocol for RNA-seq data preparation has the following steps: after RNA extraction the polyadenylated mRNA fraction is captured with oligo-dT beads. Captured RNA is fragmented and for each fragment cDNA synthesis is performed using random hexamer primers. Sequencing adapters are then ligated to each fragment. This is followed by size selection of the DNA fragments and PCR amplification. Then one end of the fragment is sequenced (single-end sequencing) or both ends (paired-end sequencing).</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "deepsage", "rna-seq"], "article_id"=>727240, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_typical_DeepSAGE_and_RNA_seq_data_generation_steps_/727240", "title"=>"Comparison of typical DeepSAGE and RNA-seq data generation steps.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-20 02:00:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095792"], "description"=>"<p>Trait-associated SNPs affecting DeepSAGE tags of 94 peripheral blood samples, but not detected in an array-based eQTL dataset of 1,469 peripheral blood samples.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "snps", "affecting", "deepsage", "tags", "94", "peripheral", "array-based", "eqtl", "dataset"], "article_id"=>727253, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.t002", "stats"=>{"downloads"=>2, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Trait_associated_SNPs_affecting_DeepSAGE_tags_of_94_peripheral_blood_samples_but_not_detected_in_an_array_based_eQTL_dataset_of_1_469_peripheral_blood_samples_/727253", "title"=>"Trait-associated SNPs affecting DeepSAGE tags of 94 peripheral blood samples, but not detected in an array-based eQTL dataset of 1,469 peripheral blood samples.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-20 02:00:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095791"], "description"=>"<p>Number of <i>cis-</i>regulated tags mapping to different genomic regions in tag-wise DeepSAGE eQTL mapping.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "tags", "genomic", "regions", "tag-wise", "deepsage", "eqtl"], "article_id"=>727252, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.t001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_cis_regulated_tags_mapping_to_different_genomic_regions_in_tag_wise_DeepSAGE_eQTL_mapping_/727252", "title"=>"Number of <i>cis-</i>regulated tags mapping to different genomic regions in tag-wise DeepSAGE eQTL mapping.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-20 02:00:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095788"], "description"=>"<p>Description of RNA next generation sequencing datasets.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "rna", "sequencing"], "article_id"=>727249, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.t005", "stats"=>{"downloads"=>3, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Description_of_RNA_next_generation_sequencing_datasets_/727249", "title"=>"Description of RNA next generation sequencing datasets.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-20 02:00:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095787"], "description"=>"*<p>This SNP was reported in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003594#pgen.1003594-CunninghameGraham1\" target=\"_blank\">[27]</a> and is validated by our data.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "polyadenylation"], "article_id"=>727248, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.t004", "stats"=>{"downloads"=>4, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SNPs_that_likely_affect_polyadenylation_due_to_a_change_in_the_polyadenylation_signal_/727248", "title"=>"SNPs that likely affect polyadenylation due to a change in the polyadenylation signal.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-20 02:00:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095785"], "description"=>"<p>The y-axis represents the number of counts for the deepSAGE tags. Two samples with different genotypes for SNP rs12934747, CC (reference allele) and TT (alternative allele), are shown as different traces. Below the coverage tracks, the position of rs12934747 is shown, together with the position of all reported polyadenylation sites from polyA_DB. An enlargement of the region containing the SNP is shown below. rs12934747 is located at the beginning of the 3′-untranslated region (3′-UTR) of <i>LPCAT2</i>, 27 nucleotides upstream a reported and experimentally validated polyadenylation site. This SNP changes the sequence, creating a polyadenylation signal that leads to the usage of the reported polyadenylation site. The square block indicates the sequence of the polyadenylation signal created by rs12934747. The creation of this signal shortens the 3′-UTR, as indicated by the higher abundance of the proximal DeepSAGE just upstream of the polyadenylation signal, and the nearly absent distal DeepSAGE, in the sample with the TT genotype (both tags indicated by arrows). Tag 2 was filtered out because it was expressed in less than 90% of individuals. There is an additional tag 3 in-between the proximal and distal tags, which is not <i>cis</i>-regulated.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "creates", "leads", "polyadenylation"], "article_id"=>727246, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.g006", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_rs12934747_T_creates_a_poly_A_signal_in_LPCAT2_and_leads_to_alternative_polyadenylation_site_usage_/727246", "title"=>"rs12934747*T creates a poly(A) signal in <i>LPCAT2</i> and leads to alternative polyadenylation site usage.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-20 02:00:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095782"], "description"=>"<p>The percentages of cis-regulated tags mapping into the same gene are indicated (781 genes overall). For nearly half of the genes (48%) only one tag shows an eQTL effect. If multiple tags map within the same gene, only one eQTL tag should pass the FDR<0.05 significance threshold while the other tag could be less significant. For these eQTLs the allelic direction is shown: same allelic direction (multiple tags within the same gene are cis-regulated by a SNP in the same direction), significantly opposite allelic direction (multiple tags within the same gene are cis-regulated by a SNP but with opposite directions and the difference between the correlation coefficients is significant), or opposite allelic direction but not significant (if the difference between correlation coefficients is not significant).</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "tags"], "article_id"=>727243, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.g004", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_number_of_cis_regulated_tags_per_gene_/727243", "title"=>"The number of <i>cis-</i>regulated tags per gene.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-20 02:00:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095796", "https://ndownloader.figshare.com/files/1095798", "https://ndownloader.figshare.com/files/1095799", "https://ndownloader.figshare.com/files/1095801", "https://ndownloader.figshare.com/files/1095802", "https://ndownloader.figshare.com/files/1095803", "https://ndownloader.figshare.com/files/1095804", "https://ndownloader.figshare.com/files/1095805", "https://ndownloader.figshare.com/files/1095806", "https://ndownloader.figshare.com/files/1095807", "https://ndownloader.figshare.com/files/1095808"], "description"=>"<div><p>Many disease-associated variants affect gene expression levels (expression quantitative trait loci, eQTLs) and expression profiling using next generation sequencing (NGS) technology is a powerful way to detect these eQTLs. We analyzed 94 total blood samples from healthy volunteers with DeepSAGE to gain specific insight into how genetic variants affect the expression of genes and lengths of 3′-untranslated regions (3′-UTRs). We detected previously unknown <i>cis</i>-eQTL effects for GWAS hits in disease- and physiology-associated traits. Apart from <i>cis</i>-eQTLs that are typically easily identifiable using microarrays or RNA-sequencing, DeepSAGE also revealed many <i>cis</i>-eQTLs for antisense and other non-coding transcripts, often in genomic regions containing retrotransposon-derived elements. We also identified and confirmed SNPs that affect the usage of alternative polyadenylation sites, thereby potentially influencing the stability of messenger RNAs (mRNA). We then combined the power of RNA-sequencing with DeepSAGE by performing a meta-analysis of three datasets, leading to the identification of many more <i>cis</i>-eQTLs. Our results indicate that DeepSAGE data is useful for eQTL mapping of known and unknown transcripts, and for identifying SNPs that affect alternative polyadenylation. Because of the inherent differences between DeepSAGE and RNA-sequencing, our complementary, integrative approach leads to greater insight into the molecular consequences of many disease-associated variants.</p></div>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "reveals", "variants", "polyadenylation", "coding", "non-coding"], "article_id"=>727257, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003594.s001", "https://dx.doi.org/10.1371/journal.pgen.1003594.s002", "https://dx.doi.org/10.1371/journal.pgen.1003594.s003", "https://dx.doi.org/10.1371/journal.pgen.1003594.s004", "https://dx.doi.org/10.1371/journal.pgen.1003594.s005", "https://dx.doi.org/10.1371/journal.pgen.1003594.s006", "https://dx.doi.org/10.1371/journal.pgen.1003594.s007", "https://dx.doi.org/10.1371/journal.pgen.1003594.s008", "https://dx.doi.org/10.1371/journal.pgen.1003594.s009", "https://dx.doi.org/10.1371/journal.pgen.1003594.s010", "https://dx.doi.org/10.1371/journal.pgen.1003594.s011"], "stats"=>{"downloads"=>59, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DeepSAGE_Reveals_Genetic_Variants_Associated_with_Alternative_Polyadenylation_and_Expression_of_Coding_and_Non_coding_Transcripts_/727257", "title"=>"DeepSAGE Reveals Genetic Variants Associated with Alternative Polyadenylation and Expression of Coding and Non-coding Transcripts", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-06-20 02:00:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095781"], "description"=>"<p>The gene biotypes and exon/intron locations of unique <i>cis</i>-regulated tags, according to Ensembl v.69 annotation, are shown. The numbers indicate the number of tags mapping in the genes of the corresponding type.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "regions"], "article_id"=>727242, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.g003", "stats"=>{"downloads"=>6, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mapping_regions_of_cis_regulated_tags_/727242", "title"=>"Mapping regions of <i>cis-</i>regulated tags.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-20 02:00:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095793"], "description"=>"*<p>Only significant eQTLs with FDR<0.05 for both <i>cis-</i>regulated tags were used.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "snps", "affecting", "tags"], "article_id"=>727254, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.t003", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cis_regulating_SNPs_significantly_affecting_multiple_tags_of_the_same_gene_in_opposite_directions_/727254", "title"=>"<i>Cis-</i>regulating SNPs significantly<sup>*</sup> affecting multiple tags of the same gene in opposite directions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-20 02:00:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095790"], "description"=>"<p>Trait-associated SNPs detected in the sequencing-based transcript-wise meta-analysis, but not detected in array-based eQTL dataset of 1,469 peripheral blood samples.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "snps", "sequencing-based", "transcript-wise", "array-based", "eqtl", "dataset", "peripheral"], "article_id"=>727251, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.t007", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Trait_associated_SNPs_detected_in_the_sequencing_based_transcript_wise_meta_analysis_but_not_detected_in_array_based_eQTL_dataset_of_1_469_peripheral_blood_samples_/727251", "title"=>"Trait-associated SNPs detected in the sequencing-based transcript-wise meta-analysis, but not detected in array-based eQTL dataset of 1,469 peripheral blood samples.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-20 02:00:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1095789"], "description"=>"<p>Number of detected <i>cis-</i>eQTLs in transcript-wise analysis of three harmonized RNA NGS datasets.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome expression analysis", "Genome analysis tools", "transcriptomes", "transcript-wise", "harmonized", "rna", "ngs"], "article_id"=>727250, "categories"=>["Biological Sciences"], "users"=>["Daria V. Zhernakova", "Eleonora de Klerk", "Harm-Jan Westra", "Anastasios Mastrokolias", "Shoaib Amini", "Yavuz Ariyurek", "Rick Jansen", "Brenda W. Penninx", "Jouke J. Hottenga", "Gonneke Willemsen", "Eco J. de Geus", "Dorret I. Boomsma", "Jan H. Veldink", "Leonard H. van den Berg", "Cisca Wijmenga", "Johan T. den Dunnen", "Gert-Jan B. van Ommen", "Peter A. C. 't Hoen", "Lude Franke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003594.t006", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_detected_cis_eQTLs_in_transcript_wise_analysis_of_three_harmonized_RNA_NGS_datasets_/727250", "title"=>"Number of detected <i>cis-</i>eQTLs in transcript-wise analysis of three harmonized RNA NGS datasets.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-20 02:00:50"}

PMC Usage Stats | Further Information

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Relative Metric

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