# Epigenetic marks and the human transcript diversity

Guillaume Devailly

► To cite this version:

Guillaume Devailly. Epigenetic marks and the human transcript diversity. Genotoul Biostat Bioinfo Day, Dec 2018, Toulouse, France. hal-01956109

HAL Id: hal-01956109

https://hal.science/hal-01956109

Submitted on 4 Jun 2020

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Distributed under a Creative Commons Attribution 4.0 International License
# Epigenetic marks and the human transcript diversity

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GenPhySE

Génétique, Physiologie et Systèmes d'Elevage

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INRA
SCIENCE & IMPACT

GenEpi@Genphyse

Guillaume Devailly - 2018/12/13

@G_Devailly
* Abundant epigenomic data for model organisms.

* Under-utilised?

* Epigenomic data will soon be abundant for agricultural species too.

Dataset:

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* RNA-seq

* DNAse1

* WGBS, 10 different histone methylations, 17 different histone acetylations

* 33 cell lines & tissues
* Systemic correlation of marks and **gene** transcription level:

* at TSS

* at TTS

* Systemic correlation of marks and **exon**:

* transcription level

* inclusion ratio

* For **all** genes/exons in **each** cell type.

* For **each** gene/exon in **all** cell types.

<figure><img src="image_5.png" /></figure>
**Processed data** taken from RoadmapEpigenomics:

* CpG methylation ratios

* DNAse-seq and ChIP-seq coverage

**Reprocessing** of fastq for Gene TPM, exon TPM & exon inclusion ratio (aka %spliced, or $\psi$):

* pseudo-mapping and quantification with Salmon

* exon $\psi$ for exon **e** of gene **g** using *tpm* quantification of transcripts **t**:

$$ \psi_{eg} = \frac{\sum_{t \subset e} tpm_t}{\sum_{t \in g} tpm_t} $$
<figure><img src="image_6.png" /></figure>

Version 22 (October 2014 freeze, GRCh38) - Ensembl 79, 80

General stats

Total No of Genes

60483
# Where is BRCA1's Transcription Start Site (TSS)?

<figure><img src="image_7.png" /></figure>
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CpG density
9 CpG/kb

2 CpG/kb

mCpG ratio
33%

100%

mCpG density
3 mCpG/kb

2 mCpG/kb
DNA methylation: ratio and density

<figure><img src="image_9.png" /><figcaption>CpG
density
mCpG %
mCpG
density
WGBS
coverage
CGI</figcaption></figure>
DNA methylation: ratio *and* density

<figure><img src="image_10.png" /><figcaption>CpG
density

mCpG %

mCpG
density

WGBS
coverage

CGI</figcaption></figure>
# Promoter DNA methylaton

Lung, all genes
Lung, protein coding genes
# Promoter DNA methylaton

<figure><img src="image_11.png" /><figcaption>## Lung, processed pseudogenes</figcaption></figure>

<figure><img src="image_12.png" /></figure>
Activating marks

<figure><img src="image_13.png" /><figcaption>H3K9ac ChIP-seq, all genes, H1-derived mesoderm</figcaption></figure>

<figure><img src="image_14.png" /></figure>
<figure><img src="image_15.png" /><figcaption>H3K27me3, all genes, Thymus</figcaption></figure>
<figure><img src="image_16.png" /><figcaption>H3K27me3, protein coding genes, Thymus</figcaption></figure>

<figure><img src="image_17.png" /></figure>
Assymmetric marks

H3K79me2, protein coding genes, H1-derived mesoderm
Exonic marks

H3K36me3, fetal large intestine
# A role in alternative splicing?

H3K36me3, HUES64 cell line

<figure><img src="image_18.png" /></figure>

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Cell by cell vs gene by gene

<figure><img src="image_20.png" /><figcaption>WGBS, adult liver</figcaption></figure>
Cell by cell vs gene by gene

WGBS, adult liver

<figure><img src="image_21.png" /></figure>

LYL1 (ENSG00000104903)

slope: -2.71

R²: 0.56

<figure><img src="image_22.png" /></figure>
mCpG ratio

<figure><img src="image_23.png" /></figure>
mCpG ratio

<figure><img src="image_24.png" /></figure>

H3K4me3

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# Summary of results

<table><thead><tr><th>mark</th><th>cell type by cell type</th><th>gene by gene</th><th>center on TSS</th></tr></thead><tbody><tr><td>WGBS</td><td>negative</td><td>negative</td><td></td></tr><tr><td>DNAse</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H2A.Z</td><td>positive</td><td>balanced</td><td></td></tr><tr><td>H3K4me1</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H3K4me2</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H3K4me3</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H3K9me3</td><td>unclear</td><td>unclear</td><td>no</td></tr><tr><td>H3K23me2</td><td>positive</td><td>NA</td><td></td></tr><tr><td>H3K27me3</td><td>negative - variable</td><td>negative</td><td></td></tr><tr><td>H3K36me3</td><td>positive</td><td>positive</td><td>no</td></tr><tr><td>H3K79me1</td><td>positive</td><td>positive</td><td>no</td></tr><tr><td>H3K79me2</td><td>positive</td><td>balanced</td><td>no</td></tr></tbody></table>

<table><thead><tr><th>mark</th><th>cell type by cell type</th><th>gene by gene</th><th>center on TSS</th></tr></thead><tbody><tr><td>H2AK5ac</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H2BK120ac</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H2BK12ac</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H2BK15ac</td><td>positive</td><td>balanced</td><td></td></tr><tr><td>H2BK20ac</td><td>neutral</td><td>NA</td><td></td></tr><tr><td>H2BK5ac</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H3K4ac</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H3K9ac</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H3K14ac</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H3K18ac</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H3K23ac</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H3K27ac</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H3K56ac</td><td>positive</td><td>NA</td><td></td></tr><tr><td>H4K8ac</td><td>positive</td><td>positive</td><td></td></tr><tr><td>H4K12ac</td><td>positive</td><td>NA</td><td></td></tr><tr><td>H4K91ac</td><td>positive</td><td>positive</td><td></td></tr></tbody></table>
Combinatorial explosion: > 9000 plots!

<figure><img src="image_26.png" /><figcaption>Figure 1: Epigenetic marks at promoters and transcription level in H1 embryonic stem cells</figcaption></figure>
## Profile Explorer of Roadmap Epigenomic data

www.perepigenomics.roslin.ed.ac.uk

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* More features (mono-, bi-, tri- exonic genes, gene families, etc.)

* More marks

* Causality analysis using perturbation experiments

* FAANG data
Anagha Joshi

Anna Mantsoki

Deepti Vipin

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PROSLIN

THE UNIVERSITY
OF EDINBURGH

THE UNIVERSITY
of EDINBURGH

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BBSRC

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CASCADE-FELLOWS

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Génétique, Physiologie et Systèmes d'Elevage

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INRA
SCIENCE & IMPACT