Recounting the FANTOM CAGE-Associated Transcriptome

Imada, Eddie Luidy; Sánchez, Diego F.; Collado‐Torres, Leonardo; Wilks, Christopher; Matam, Tejasvi; Dinalankara, Wikum; Stupnikov, Alexey; Lobo-Pereira, Francisco; Yip, Chi Wai; Yasuzawa, Kayoko; Kondo, Naoto; Itoh, Masayoshi; Suzuki, Harukazu; Kasukawa, Takeya; Hon, Chung-Chau; Hoon, Michiel de; Shin, Jay W.; Carninci, Piero; Jaffe, Andrew E.; Leek, Jeffrey T.; Favorov, Alexander V.; Franco, Glória Regina; Langmead, Ben; Marchionni, Luigi

doi:10.1101/gr.254656.119

Cited by 26 publications

(35 citation statements)

References 49 publications

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“…As these results indicated a potential role of ZNF213-AS1 in cell growth and migration, we used FANTOM CAT Recount 2 atlas (Imada et al 2020), which incorporates The Cancer Genome Atlas (TCGA) data set (Collado-Torres et al 2017), and found relatively higher expression of ZNF213-AS1 in acute myeloid leukemia (LAML) and in low-grade gliomas (LGG) as compared to other cancers (Supplemental Fig. S6A).…”

Section: Znf213-as1 Is Associated With Cell Growth and Migrationmentioning

confidence: 99%

Functional annotation of human long noncoding RNAs via molecular phenotyping

et al. 2020

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Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-todate lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.

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Section: Znf213-as1 Is Associated With Cell Growth and Migrationmentioning

confidence: 99%

Functional annotation of human long noncoding RNAs via molecular phenotyping

et al. 2020

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“…We recently developed a comprehensive expression atlas based on the FANTOM-CAT annotations. This meta-assembly is currently the broadest collection of the human transcriptome (21,36). These gene models include many novel lncRNA categories such as enhancers and promoters, allowing the signature to be further expanded beyond the coding repertoire.…”

Section: Extending the Pten-loss Signaturementioning

confidence: 99%

“…Overall, this PTEN-loss signature was associated with cellular processes associated with aggressive tumor behavior (e.g., increased motility and proliferation) and, surprisingly, with increases in gene sets related to the immune response. In addition, through our recently developed FANTOM-CAT/recount2 (FC-R2) resource (21) and copy-number-variation data, we expanded this signature beyond coding genes and report the non-coding RNA repertory resulting from PTEN loss.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional landscape of PTEN loss in primary prostate cancer

Imada

Sánchez

Dinalankara

et al. 2020

Preprint

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PTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. Here, we applied a meta-analysis approach, leveraging two large PCa cohorts with experimentally validated PTEN and ERG status, to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. Strikingly, the signature indicates a strong activation of both innate and adaptive immune systems upon PTEN loss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. With this resource, we analyzed the TCGA-PRAD cohort, creating a comprehensive transcriptomic landscape of PTEN loss in PCa that comprises both the coding and an extensive non-coding counterpart.

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“…The FANTOM5 project also used CAGE to annotate TSSs in mammalian genomes (Andersson et al, 2014; Forrest et al, 2014b; Imada et al, 2020). The FANTOM5 data release contained putative TSSs for human, mouse, chicken, rhesus monkey and dog (https://fantom.gsc.riken.jp/5/data/).…”

Section: Resultsmentioning

confidence: 99%

Global analysis of transcription start sites in the new ovine reference genome (Oar rambouillet v1.0)

Salavati

Caulton

Clark

et al. 2020

Preprint

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AbstractThe overall aim of the Ovine FAANG project is to provide a comprehensive annotation of the new highly contiguous sheep reference genome sequence (Oar rambouillet v1.0). Mapping of transcription start sites (TSS) is a key first step in understanding transcript regulation and diversity. Using 56 tissue samples collected from the reference ewe Benz2616 we have performed a global analysis of TSS and TSS-Enhancer clusters using Cap Analysis Gene Expression (CAGE) sequencing. CAGE measures RNA expression by 5’ cap-trapping and has been specifically designed to allow the characterization of TSS within promoters to single-nucleotide resolution. We have adapted an analysis pipeline that uses TagDust2 for clean-up and trimming, Bowtie2 for mapping, CAGEfightR for clustering and the Integrative Genomics Viewer (IGV) for visualization. Mapping of CAGE tags indicated that the expression levels of CAGE tag clusters varied across tissues. Expression profiles across tissues were validated using corresponding polyA+ mRNA-Seq data from the same samples. After removal of CAGE tags with < 10 read counts, 39.3% of TSS overlapped with 5’ ends of transcripts, as annotated previously by NCBI. A further 14.7% mapped to within 50bp of annotated promoter regions. Intersecting these predicted TSS regions with annotated promoter regions (±50bp) revealed 46% of the predicted TSS were ‘novel’ and previously un-annotated. Using whole genome bisulphite sequencing data from the same tissues we were able to determine that a proportion of these ‘novel’ TSS were hypo-methylated (32.2%) indicating that they are likely to be reproducible rather than ‘noise’. This global analysis of TSS in sheep will significantly enhance the annotation of gene models in the new ovine reference assembly. Our analyses provide one of the highest resolution annotations of transcript regulation and diversity in a livestock species to date.

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Recounting the FANTOM CAGE-Associated Transcriptome

Cited by 26 publications

References 49 publications

Functional annotation of human long noncoding RNAs via molecular phenotyping

Functional annotation of human long noncoding RNAs via molecular phenotyping

Transcriptional landscape of PTEN loss in primary prostate cancer

Global analysis of transcription start sites in the new ovine reference genome (Oar rambouillet v1.0)

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