PEREpigenomics

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# PEREpigenomics
## Profile Explorer of Roadmap Epigenomics data
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[@G_Devailly](https://twitter.com/G_Devailly) 
Guillaume Devailly 
useR!2019 
2019/07/09
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![:img_scale 80%](img/genphyse_inra_logo.png)
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# One genome, many cell types

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![](img/bioRender.png)
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Differential gene expression =  
cellular environment + epigenetics
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# Epigenetics data

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Many existing datasets and databases.
## Dataset: ![](img/RoadmapEpigenomics.png)
- RNA-seq
- DNAse1
- WGBS,
- 10 different histone methylations
- 17 different histone acetylations

in 33 human cell lines & tissues, uniformly processed.
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![](img/main_illustration.png)
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# What to do with big dataset?

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Build a data portal:
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![:img_scale 80%](img/data_portal_roadmap.png)
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# What to do with big dataset?

Link data to genome browser:
.center[![:img_scale 65%](img/browser_2.png)]

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# What to do with big dataset?

Machine learning:
![](img/ml_re.png)

.right[.font60[Kundaje, Meuleman, Ernst, Bilenky et al., 2015, [10.1038/nature14248](https://doi.org/10.1038/nature14248)]]

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# Objectives

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- Visualisation of marks, sorted by **gene** transcription level:
  - at TSS (gene start)
  - at TTS (gene end)
- Visualisation of marks at **middle exons** starts, sorted by:
  - transcription level
  - inclusion ratio
- For **all** genes/exons in **each** cell type.
- For **each** gene/exon in **all** cell types.
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![:img_scale 85%](img/h3k4me3_SI.png)
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# H3K4me3, TSS, small intestine

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![:img_scale 47%](img/h3k4me3_SI.png)
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# Different gene types, different associations
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lincRNA  
![:img_scale 75%](img/h3k4me3_SI_lincRNA.png)
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processed pseudogenes  
![:img_scale 75%](img/h3k4me3_SI_propseudo.png)
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# Position of signal matters
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DNAse 1 (accessible chromatin)  
![:img_scale 75%](img/DNAse_SI.png)
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H3K27ac  
![:img_scale 75%](img/h3k27ac_SI.png)
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# Exonic mark: H3K36me3, fetal large intestine

![:img_scale 45%](img/H3K36me3.png)

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# DNA methylation: ratio *and* density

![:img_scale 100%](img/dname_ex1.png)

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# Exonic DNA methylation

WGBS, pancreas  
![:img_scale 60%](img/wgbs_panc_E098_all.png)

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# Cell by cell *vs* gene by gene

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WGBS, adult liver
![](img/wgbs_TSS_gene_FPKM_E066_all.png)
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]

---
# Repressing and activating marks

.pull-left[
### mCpG ratio
![:img_scale 80%](img/all_genes_wgbs.png)
]

.pull-right[
### H3K4me3
![:img_scale 80%](img/all_genes_h3k4.png)
]

---
class: inverse, center

# Too many plots?

.center[
![:img_scale 75%](img/explosion.png)
]

---
# PEREpigenomics

*P*rofile *E*xplorer of *R*oadmap *Epigenomic* data  
[www.perepigenomics.roslin.ed.ac.uk](http://www.perepigenomics.roslin.ed.ac.uk/)

.center[
![:img_scale 50%](img/perepigenomics.png)
]

---
# Summary of results

.pull-left[
<table class="table table-striped" style="font-size: 14px; width: auto !important; margin-left: auto; margin-right: auto;">
 <thead>
 <tr>
 <th style="text-align:left;"> mark </th>
 <th style="text-align:left;"> cell type by cell type </th>
 <th style="text-align:left;"> gene by gene </th>
 <th style="text-align:left;"> center on TSS </th>
 </tr>
 </thead>
<tbody>
 <tr>
 <td style="text-align:left;"> WGBS </td>
 <td style="text-align:left;"> negative </td>
 <td style="text-align:left;"> negative </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> DNAse </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H2A.Z </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> balanced </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K4me1 </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K4me2 </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K4me3 </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K9me3 </td>
 <td style="text-align:left;"> unclear </td>
 <td style="text-align:left;"> unclear </td>
 <td style="text-align:left;"> no </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K23me2 </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> NA </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K27me3 </td>
 <td style="text-align:left;"> negative – variable </td>
 <td style="text-align:left;"> negative </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K36me3 </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> no </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K79me1 </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> no </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K79me2 </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> balanced </td>
 <td style="text-align:left;"> no </td>
 </tr>
</tbody>
</table>
]

.pull-right[
<table class="table table-striped" style="font-size: 14px; width: auto !important; margin-left: auto; margin-right: auto;">
 <thead>
 <tr>
 <th style="text-align:left;"> mark </th>
 <th style="text-align:left;"> cell type by cell type </th>
 <th style="text-align:left;"> gene by gene </th>
 <th style="text-align:left;"> center on TSS </th>
 </tr>
 </thead>
<tbody>
 <tr>
 <td style="text-align:left;"> H2AK5ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H2BK120ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H2BK12ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H2BK15ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> balanced </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H2BK20ac </td>
 <td style="text-align:left;"> neutral </td>
 <td style="text-align:left;"> NA </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H2BK5ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K4ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K9ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K14ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K18ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K23ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K27ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H3K56ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> NA </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H4K8ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H4K12ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> NA </td>
 <td style="text-align:left;"> </td>
 </tr>
 <tr>
 <td style="text-align:left;"> H4K91ac </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> positive </td>
 <td style="text-align:left;"> </td>
 </tr>
</tbody>
</table>

]

---
class: font180

## Conclusions

PEREpigenomics offers interesting visualisations of epigenetic data gathered by
Roadmap Epigenomics.

## Perspectives

- update with new annotation data (ongoing)
- preprint & source code available soon
- develop similar approach for [FAANG](http://data.faang.org/home) (Functional Annotation of the Animal Genomes) data

---
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class: font180
# Thanks

.pull-left[
Anagha Joshi

Anna Mantsoki

Deepti Vipin
]

.pull-right[
![:img_scale 100%](img/logo_all.png)
]