Transcriptome and proteome quantification of a tumor model provides novel insights into post‐transcriptional gene regulation

Jüschke, Christoph; Dohnal, Ilse; Pichler, Peter; Harzer, Heike; Swart, Remco; Ammerer, Gustav; Mechtler, Karl; Knoblich, Juergen A.

doi:10.1186/gb-2013-14-11-r133

Cited by 48 publications

(50 citation statements)

References 77 publications

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“…A recent study by Jüschke et al (2013) reported similar results in Drosophila spp. : about 82% of all Kyoto Encyclopedia of Genes and Genomes annotated transcripts were expressed in fly heads, while 18% were not expressed.…”

Section: Discussionsupporting

confidence: 73%

Digital Inventory of Arabidopsis Transcripts Revealed by 61 RNA Sequencing Samples

et al. 2014

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Alternative splicing is an essential biological process to generate proteome diversity and phenotypic complexity. Recent improvements in RNA sequencing accuracy and computational algorithms have provided unprecedented opportunities to examine the expression levels of Arabidopsis (Arabidopsis thaliana) transcripts. In this article, we analyzed 61 RNA sequencing samples from 10 totally independent studies of Arabidopsis and calculated the transcript expression levels in different tissues, treatments, developmental stages, and varieties. These data provide a comprehensive profile of Arabidopsis transcripts with single-base resolution. We quantified the expression levels of 40,745 transcripts annotated in The Arabidopsis Information Resource 10, comprising 73% common transcripts, 15% rare transcripts, and 12% nondetectable transcripts. In addition, we investigated diverse common transcripts in detail, including ubiquitous transcripts, dominant/subordinate transcripts, and switch transcripts, in terms of their expression and transcript ratio. Interestingly, alternative splicing was the highly enriched function for the genes related to dominant/subordinate transcripts and switch transcripts. In addition, motif analysis revealed that TC motifs were enriched in dominant transcripts but not in subordinate transcripts. These motifs were found to have a strong relationship with transcription factor activity. Our results shed light on the complexity of alternative splicing and the diversity of the contributing factors.

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Section: Discussionsupporting

confidence: 73%

Digital Inventory of Arabidopsis Transcripts Revealed by 61 RNA Sequencing Samples

et al. 2014

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“…50,53 Reliable quantification of post-transcriptional regulation remains a significant computational challenge. Here, we developed a resampling-based regression method to reliably quantify differential post-transcriptional regulation associated with MSI status.…”

Section: Resultsmentioning

confidence: 99%

Integrative Omics Analysis Reveals Post-Transcriptionally Enhanced Protective Host Response in Colorectal Cancers with Microsatellite Instability

Liu

Zhang

2015

J. Proteome Res.

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Microsatellite instability (MSI) is a frequent and clinically relevant molecular phenotype in colorectal cancer. MSI cancers have favorable survival compared with microsatellite stable cancers (MSS), possibly due to the pronounced tumor-infiltrating lymphocytes observed in MSI cancers. Consistent with the strong immune response that MSI cancers trigger in the host, previous transcriptome expression studies have identified mRNA signatures characteristic of immune response in MSI cancers. However, proteomics features of MSI cancers and the extent to which the mRNA signatures are reflected at the protein level remain largely unknown. Here, we performed a comprehensive comparison of global proteomics profiles between MSI and MSS colorectal cancers in The Cancer Genome Atlas (TCGA) cohort. We found that protein signatures of MSI are also associated with increased immunogenicity. To reliably quantify post-transcription regulation in MSI cancers, we developed a resampling-based regression method by integrative modeling of transcriptomics and proteomics data sets. Compared with the popular simple method, which detects post-transcriptional regulation by either identifying genes differentially expressed at the mRNA level but not at the protein level or vice versa, our method provided a quantitative, more sensitive, and accurate way to identify genes subject to differential post-transcriptional regulation. With this method, we demonstrated that post-transcriptional regulation, coordinating protein expression with key players, initiates de novo and enhances protective host response in MSI cancers.

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“…In addition to studying steady state mRNA and protein abundance, there are increasing research activities on the alterations of mRNA and protein abundance due to changing conditions or genetic variations, and dynamic changes in response to perturbations . Comparative analyses of proteomic and transcriptomic alterations provide a great opportunity to (1) investigate whether changing transcript abundance mediates protein alterations; (2) identify genes and functional categories with discordant mRNA‐protein alterations, suggesting potential protein‐level regulations; (3) discover the underlying regulators responsible for the protein‐level regulations.…”

Section: Integrative Analysis Of Mrna and Protein Abundancementioning

confidence: 99%

Leveraging the complementary nature of RNA‐Seq and shotgun proteomics data

2014

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RNA sequencing (RNA-Seq) and mass spectrometry-based shotgun proteomics are powerful high-throughput technologies for identifying and quantifying RNA transcripts and proteins respectively. With the increasing affordability of these technologies, many projects have started to apply both to the same samples to achieve a more comprehensive understanding of biological systems. A major analytical challenge for such integrative projects is how to effectively leverage the complementary nature of RNA-Seq and shotgun proteomics data. RNA-Seq provides comprehensive information on mRNA abundance, alternative splicing, nucleotide variation and structure alteration. Sample-specific protein databases derived from RNA-Seq data can better approximate the real protein pools in cell and tissue samples and thus improve protein identification. Meanwhile, proteomics data provides essential confirmation of the validity and functional relevance of novel findings from RNA-Seq data. At the quantitative level, mRNA and protein levels are only modestly correlated, suggesting strong involvement of post-transcriptional regulation in controlling gene expression. Here we review recent studies at the interface of RNA-Seq and proteomics data. We discuss goals, accomplishments and challenges in RNA-Seq-based proteogenomics. We also examine the current status and future potential of parallel transcriptome and proteome quantification in revealing post-transcriptional regulatory mechanisms.

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Transcriptome and proteome quantification of a tumor model provides novel insights into post‐transcriptional gene regulation

Cited by 48 publications

References 77 publications

Digital Inventory of Arabidopsis Transcripts Revealed by 61 RNA Sequencing Samples

Digital Inventory of Arabidopsis Transcripts Revealed by 61 RNA Sequencing Samples

Integrative Omics Analysis Reveals Post-Transcriptionally Enhanced Protective Host Response in Colorectal Cancers with Microsatellite Instability

Leveraging the complementary nature of RNA‐Seq and shotgun proteomics data

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