Article

GENCODE: The reference human genome annotation for The ENCODE Project.

Wellcome Trust Sanger Institute, Wellcome Trust Campus, Hinxton, Cambridge CB10 1SA, United Kingdom
Genome Research (Impact Factor: 13.85). 01/2012; 22:1760-74. DOI: 10.1101/gr.135350.111

ABSTRACT The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq. It also has the most comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA-seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers

0 Followers
 · 
236 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Current prostate cancer (PCa) biomarkers such as PSA are not optimal in distinguishing cancer from benign prostate diseases and predicting disease outcome. To discover additional biomarkers, we investigated PCa-specific expression of novel unannotated transcripts. Using the unique probe design of Affymetrix Human Exon Arrays, we identified 334 candidates (EPCATs), of which 15 were validated by RT-PCR. Combined into a diagnostic panel, 11 EPCATs classified 80% of PCa samples correctly, while maintaining 100% specificity. High specificity was confirmed by in situ hybridization for EPCAT4R966 and EPCAT2F176 (SChLAP1) on extensive tissue microarrays. Besides being diagnostic, EPCAT2F176 and EPCAT4R966 showed significant association with pT-stage and were present in PIN lesions. We also found EPCAT2F176 and EPCAT2R709 to be associated with development of metastases and PCa-related death, and EPCAT2F176 to be enriched in lymph node metastases. Functional significance of expression of 9 EPCATs was investigated by siRNA transfection, revealing that knockdown of 5 different EPCATs impaired growth of LNCaP and 22RV1 PCa cells. Only the minority of EPCATs appear to be controlled by androgen receptor or ERG. Although the underlying transcriptional regulation is not fully understood, the novel PCa-associated transcripts are new diagnostic and prognostic markers with functional relevance to prostate cancer growth.
    Oncotarget 01/2015; · 6.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: DNase I hypersensitive sites (DHSs) define the accessible chromatin landscape and have revolutionised the discovery of distinct cis-regulatory elements in diverse organisms. Here, we report the first comprehensive map of human transcription factor binding site (TFBS)-clustered regions using Gaussian kernel density estimation based on genome-wide mapping of the TFBSs in 133 human cell and tissue types. Approximately 1.6 million distinct TFBS-clustered regions, collectively spanning 27.7% of the human genome, were discovered. The TFBS complexity assigned to each TFBS-clustered region was highly correlated with genomic location, cell selectivity, evolutionary conservation, sequence features, and functional roles. An integrative analysis of these regions using ENCODE data revealed transcription factor occupancy, transcriptional activity, histone modification, DNA methylation, and chromatin structures that varied based on TFBS complexity. Furthermore, we found that we could recreate lineage-branching relationships by simple clustering of the TFBS-clustered regions from terminally differentiated cells. Based on these findings, a model of transcriptional regulation determined by TFBS complexity is proposed.
    Scientific Reports 02/2015; 5:8465. DOI:10.1038/srep08465 · 5.08 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: // René Böttcher1,3, A. Marije Hoogland2, Natasja Dits1, Esther I. Verhoef2, Charlotte Kweldam2, Piotr Waranecki1, Chris H. Bangma1, Geert J.L.H. van Leenders2, Guido Jenster1 1Dept. of Urology, Erasmus MC, Rotterdam, The Netherlands 2Dept. of Pathology, Erasmus MC, Rotterdam, The Netherlands 3Dept. of Bioinformatics, Technical University of Applied Sciences Wildau, Wildau, Germany Correspondence to: Guido Jenster, e-mail: g.jenster@erasmusmc.nl Keywords: Long non-coding RNA, prostate cancer, in situ hybridization, exon array, biomarkers Received: August 22, 2014 Accepted: December 08, 2014 Published: January 22, 2015 ABSTRACT Current prostate cancer (PCa) biomarkers such as PSA are not optimal in distinguishing cancer from benign prostate diseases and predicting disease outcome. To discover additional biomarkers, we investigated PCa-specific expression of novel unannotated transcripts. Using the unique probe design of Affymetrix Human Exon Arrays, we identified 334 candidates (EPCATs), of which 15 were validated by RT-PCR. Combined into a diagnostic panel, 11 EPCATs classified 80% of PCa samples correctly, while maintaining 100% specificity. High specificity was confirmed by in situ hybridization for EPCAT4R966 and EPCAT2F176 (SChLAP1) on extensive tissue microarrays. Besides being diagnostic, EPCAT2F176 and EPCAT4R966 showed significant association with pT-stage and were present in PIN lesions. We also found EPCAT2F176 and EPCAT2R709 to be associated with development of metastases and PCa-related death, and EPCAT2F176 to be enriched in lymph node metastases. Functional significance of expression of 9 EPCATs was investigated by siRNA transfection, revealing that knockdown of 5 different EPCATs impaired growth of LNCaP and 22RV1 PCa cells. Only the minority of EPCATs appear to be controlled by androgen receptor or ERG. Although the underlying transcriptional regulation is not fully understood, the novel PCa-associated transcripts are new diagnostic and prognostic markers with functional relevance to prostate cancer growth.
    Oncotarget 01/2015; 6(6). · 6.63 Impact Factor

Full-text

Download
89 Downloads
Available from
May 26, 2014