2018 Fiscal Year Annual Research Report
Role of retrotransposon in genome plasticity and diseases
| Project/Area Number |
18F18721
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| Research Institution | Institute of Physical and Chemical Research |
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| Host Researcher |
Carninci Piero 国立研究開発法人理化学研究所, 生命医科学研究センター, 副センター長 (10333296)
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| Foreign Research Fellow |
ROBBE PAULINE 国立研究開発法人理化学研究所, 生命医科学研究センター, 外国人特別研究員
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| Project Period (FY) |
2018-07-25 – 2021-03-31
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| Keywords | Transcriptomics / Genomics / Cancer / Non-coding RNA / Non-coding mutations |
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| Outline of Annual Research Achievements |
The initial project has been changed since I started my JSPS fellowship, because of recent findings and long discussions with the host lab.
I spent the first two months studying the research of the host lab. I met collaborators working in Hepatocellular carcinoma (HCC) and planed a new project.
Recent findings highlighted examples of non-coding somatic mutations dysregulating enhancers, leading to aggressive cancers. Enhancers are key regulatory elements controlling the transcription of protein-coding genes using enhancer RNA (eRNA). Active enhancers are cell-type-specific and they have no accurate map. Therefore, non-coding mutations dysregulating eRNA expression and target genes cannot be investigated. The aims are to:
1. Construct a map of enhancers in HCC
2. identify HCC specific non-coding somatic mutations in enhancers, affecting their activity and the activity of their target protein coding-genes
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Using hepatocellular carcinoma (HCC) as a model, the aims are to: (1) construct an map of enhancers using Cap Analysis Gene Expression (CAGE); (2) identify non-coding somatic mutations in enhancers affecting their activity (measuring eRNA transcription) and the activity of their target protein coding-genes, using an integrated approach of whole genome sequencing and strand-specific RNA sequencing.
Summary of my progress to date:
- I have completed Aim 1: I have constructed a bioinformatics pipeline to analyze CAGE data and defined a robust and permissive maps of HCC specific enhancers. The results need discussion and revision.
- I have prepared for Aim 2: I prepared a list of non-coding somatic mutations from WGS. I have started to familiarize myself with RNA-seq data.
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| Strategy for Future Research Activity |
Aim 2. Identify non-coding somatic mutations in enhancers affecting their activity and the transcription of their target protein-coding genes in the context of HCC
- Link 1 co-localisation. I will calculate a count table summarising eRNA expression using RNA-seq data. I will select enhancers with both somatic variants and expression change.
- Link 2 co-expression. To link enhancers to target genes two approaches will be used: regulatory networks from public data and co-expression analysis to infer regulatory networks between enhancer and coding-gene expression. The dysregulated enhancers leading to a change of expression in the target gene will be selected.
- Data integration and validation. The impact on patient survival of selected enhancers recurrently dysregulated will be assessed. Experiments will validate the enhancers-gene links.
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