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Widespread and Functional RNA Circularization in Localized Prostate Cancer.

Cell | 2019

The cancer transcriptome is remarkably complex, including low-abundance transcripts, many not polyadenylated. To fully characterize the transcriptome of localized prostate cancer, we performed ultra-deep total RNA-seq on 144 tumors with rich clinical annotation. This revealed a linear transcriptomic subtype associated with the aggressive intraductal carcinoma sub-histology and a fusion profile that differentiates localized from metastatic disease. Analysis of back-splicing events showed widespread RNA circularization, with the average tumor expressing 7,232 circular RNAs (circRNAs). The degree of circRNA production was correlated to disease progression in multiple patient cohorts. Loss-of-function screening identified 11.3% of highly abundant circRNAs as essential for cell proliferation; for ∼90% of these, their parental linear transcripts were not essential. Individual circRNAs can have distinct functions, with circCSNK1G3 promoting cell growth by interacting with miR-181. These data advocate for adoption of ultra-deep RNA-seq without poly-A selection to interrogate both linear and circular transcriptomes.

Pubmed ID: 30735634 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

Associated grants

  • Agency: CIHR, Canada
    Id: 146586
  • Agency: CIHR, Canada
    Id: 142246
  • Agency: CIHR, Canada
    Id: 152863
  • Agency: CIHR, Canada
    Id: 152864
  • Agency: CIHR, Canada
    Id: 159567

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This is a list of tools and resources that we have found mentioned in this publication.


RSeQC (tool)

RRID:SCR_005275

Software package to comprehensively evaluate different aspects of RNA-seq experiments, such as sequence quality, GC bias, polymerase chain reaction bias, nucleotide composition bias, sequencing depth, strand specificity, coverage uniformity and read distribution over the genome structure. RSeQC takes both SAM and BAM files as input, which can be produced by most RNA-seq mapping tools as well as BED files, which are widely used for gene models.

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New England Biolabs (tool)

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DDEF1 (P7Q) (antibody)

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PSD3 antibody (antibody)

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GAPDH Antibody (0411) (antibody)

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GOLPH3 antibody (antibody)

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RPS6KC1 Polyclonal Antibody (antibody)

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CKI gamma 3 antibody - Carboxyterminal end (antibody)

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edgeR (software resource)

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GenomicFeatures (software resource)

RRID:SCR_016960

Software R package for making and manipulating transcript centric annotations. Used to download the genomic locations of the transcripts, exons and cds of a given organism, from either the UCSC Genome Browser or a BioMart database.

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FusionCatcher (software resource)

RRID:SCR_000060

Software that searches for novel/known fusion genes, translocations, and chimeras in RNA-seq data (paired-end reads from Illumina NGS platforms like Solexa and HiSeq) from diseased samples.

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clusterProfiler (software resource)

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Software R package for statistical analysis and visualization of functional profiles for genes and gene clusters.

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ggplot2 (data processing software)

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Open source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.

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FastQC (software resource)

RRID:SCR_014583

Quality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.

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ConsensusClusterPlus (software resource)

RRID:SCR_016954

Software written in R for determining cluster count and membership by stability evidence in unsupervised analysis. Provides quantitative and visual stability evidence for estimating the number of unsupervised classes in a dataset with item tracking, item consensus and cluster consensus plots.

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22Rv1 (cell line)

RRID:CVCL_1045

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HCT 116 (cell line)

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TopHat-Fusion (software resource)

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An algorithm for Discovery of Novel Fusion Transcripts with the ability to align reads across fusion points, which results from the breakage and re-joining of two different chromosomes, or from rearrangements within a chromosome.

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RSEM (software resource)

RRID:SCR_013027

Software package for quantifying gene and isoform abundances from single end or paired end RNA Seq data. Accurate transcript quantification from RNA Seq data with or without reference genome. Used for accurate quantification of gene and isoform expression from RNA-Seq data.

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STAR (software resource)

RRID:SCR_015899

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TopHat (software resource)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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CIRCexplorer (data analysis software)

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View all literature mentions

ggplot2 (data processing software)

RRID:SCR_014601

Open source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.

View all literature mentions

R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions

RandomForest Package in R (software resource)

RRID:SCR_015718

Software package for classification and regression based on a forest of trees using random inputs.

View all literature mentions

clusterProfiler (software resource)

RRID:SCR_016884

Software R package for statistical analysis and visualization of functional profiles for genes and gene clusters.

View all literature mentions

CIRCexplorer (data analysis software)

RRID:SCR_016893

Software tool as a combined strategy to identify junction reads from back spliced exons and intron lariats. Computational pipeline to precisely identify junction reads from Circularized Exons. Used to identify circular RNAs (circRNAs and ciRNAs).

View all literature mentions

ConsensusClusterPlus (software resource)

RRID:SCR_016954

Software written in R for determining cluster count and membership by stability evidence in unsupervised analysis. Provides quantitative and visual stability evidence for estimating the number of unsupervised classes in a dataset with item tracking, item consensus and cluster consensus plots.

View all literature mentions

TopHat-Fusion (software resource)

RRID:SCR_011899

An algorithm for Discovery of Novel Fusion Transcripts with the ability to align reads across fusion points, which results from the breakage and re-joining of two different chromosomes, or from rearrangements within a chromosome.

View all literature mentions

TopHat (software resource)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

View all literature mentions

FastQC (software resource)

RRID:SCR_014583

Quality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.

View all literature mentions

FusionCatcher (software resource)

RRID:SCR_000060

Software that searches for novel/known fusion genes, translocations, and chimeras in RNA-seq data (paired-end reads from Illumina NGS platforms like Solexa and HiSeq) from diseased samples.

View all literature mentions

GenomicFeatures (software resource)

RRID:SCR_016960

Software R package for making and manipulating transcript centric annotations. Used to download the genomic locations of the transcripts, exons and cds of a given organism, from either the UCSC Genome Browser or a BioMart database.

View all literature mentions

edgeR (software resource)

RRID:SCR_012802

Bioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.

View all literature mentions

STAR (software resource)

RRID:SCR_015899

Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.

View all literature mentions

RSEM (software resource)

RRID:SCR_013027

Software package for quantifying gene and isoform abundances from single end or paired end RNA Seq data. Accurate transcript quantification from RNA Seq data with or without reference genome. Used for accurate quantification of gene and isoform expression from RNA-Seq data.

View all literature mentions

HCT 116 (cell line)

RRID:CVCL_0291

Cell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

PC-3 (cell line)

RRID:CVCL_0035

Cell line PC-3 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

LNCaP clone FGC (cell line)

RRID:CVCL_1379

Cell line LNCaP clone FGC is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions