Methods in computational epigenetics

# Methods in computational epigenetics

Nathan Sheffield

<span style="font-size:0.6em"><a href="http://www.databio.org/slides">www.databio.org/slides</a></span>

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# Mission statement

We develop and apply computational methods<br/>
to organize, analyze, and understand large epigenomic data.<br/><br/>
<img src="/_modules/mission-statement/understand.svg" width="695">
<br> <img src="/_modules/mission-statement/logo_databio.svg" width="195">
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# Biological motivation

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<br><br>
<img src="/_modules/bio-motivation-regulatory-dna/dna_folding_diversity.svg" width="400"><br/>
Cells alter phenotype by using DNA differently. <br>
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<div class="col2 fragment">
<img src="/_modules/bio-motivation-regulatory-dna/differentation_gone_awry.svg" width="500"><br/>
Breakdowns lead to disease
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# Full-stack bioinformatics

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# Full-stack bioinformatics

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# Full-stack bioinformatics

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# Full-stack bioinformatics

<div class="col2">
<img src="/_modules/full-stack-bioinformatics/pyramid_algorithms.svg" width="500"><br>
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<div class="col2">
Augmented Interval List
<img src="/_modules/full-stack-bioinformatics/ailist_summary.svg" width="450"><br>
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# Full-stack bioinformatics

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# Full-stack bioinformatics

<div class="col2">
<img src="/_modules/full-stack-bioinformatics/pyramid_analysis.svg" width="500"><br>
</div>
<div class="col2">
Analysis of DNA methylation  
in Ewing sarcoma<br/>
<img src="/_modules/full-stack-bioinformatics/analysis_ews.svg" height="450"><br>
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# Full-stack bioinformatics

<div class="col2">
<img src="/_modules/full-stack-bioinformatics/pyramid_yellow.svg" width="500"><br>
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<div class="col2">
<img src="/_modules/full-stack-bioinformatics/integration.svg" width="500"><br>
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### Locus Overlap Analysis

<div class="small">
<a href="http://code.databio.org/LOLA/">http://code.databio.org/LOLA/</a><br>
</div>
<span class="small bullet"><img src="/_modules/lola-intro/paper.svg" height="25" class="bullet">Sheffield and Bock (2016). <i>Bioinformatics</i>.</span><br/>
<span class="small bullet"><img src="/_modules/lola-intro/paper.svg" height="25" class="bullet">Nagraj, Magee, and Sheffield (2018). <i>Nucleic Acids Research</i>.</span>
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<div class="small">
<a href="http://code.databio.org/LOLA/">http://code.databio.org/LOLA/</a><br>
</div>

<span style="font-size: 0.8em;"><img src="/shorts/lola/paper.svg" height="25" style="vertical-align: text-bottom; margin-right: 5px;">Sheffield and Bock (2016). *Bioinformatics*.</span><br/>
<span style="font-size: 0.8em;"><img src="/shorts/lola/paper.svg" height="25" style="vertical-align: text-bottom; margin-right: 5px;">Nagraj, Magee, and Sheffield (2018). *Nucleic Acids Research*.</span>

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![New data](/shorts/lola/01-new-data.svg)

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![New data connection](/shorts/lola/02-new-data-connection.svg)

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![GSEA](/shorts/lola/03-gsea.svg)

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![HTS](/shorts/lola/04-hts.svg)

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![Convert](/shorts/lola/05-convert.svg)

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![Introducing LOLA](/shorts/lola/06-introducing-lola.svg)

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![LOLA 1](/shorts/lola/07-lola1.svg)

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![LOLA 2](/shorts/lola/08-lola2.svg)

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![Test](/shorts/lola/09-test.svg)

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![Results](/shorts/lola/10-results.svg)

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![EWS vs others 2](/shorts/lola/ews_vs_others2.svg)

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![EWS vs others 3](/shorts/lola/ews_vs_others3.svg)

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## LOLAweb

A shiny app and server for interactive LOLA analysis.

Public server: [http://lolaweb.databio.org](http://lolaweb.databio.org)

GitHub: [https://github.com/databio/LOLAweb](https://github.com/databio/LOLAweb)

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### DEMO

<video controls width="800">
  <source src="lw.webm" type="video/webm">
Your browser does not support the video tag.
</video>
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## Methylation-based Inference of Regulatory Activity (MIRA)

<div class="small">
<a href="http://code.databio.org/MIRA/">http://code.databio.org/MIRA/</a><br>
</div>
<span class="small bullet"><img src="/_modules/mira/icons/paper.svg" height="25" class="bullet">Lawson et al. (2018). <i>Bioinformatics</i>.</span>
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<div class="small">
<a href="{{project_url}}">{{project_url}}</a><br>
</div>
<span class="small bullet"><img src="/_modules/project-cover/icons/paper.svg" height="25" class="bullet" style="vertical-align: text-bottom; margin-right: 5px;">{{project_citations}}</span>
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## MIRA concept

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## MIRA workflow

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## MIRA analysis

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## MIRA results: Differential activity

<span class="small bullet"><img src="/_modules/mira/icons/paper.svg" height="25" class="bullet">Sheffield et al. (2017). <i>Nature Medicine</i>.</span>

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## MIRA results: Activity scores

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## MIRA results: Enrichment analysis

<img src="/_modules/mira/ews_pat/MIRA_result_3.svg" width="800"/>
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## Coordinate Covariation Analysis (COCOA)

<div class="small">
<a href="http://code.databio.org/COCOA/">http://code.databio.org/COCOA/</a><br>
</div>

<span class="small bullet"><img src="/_modules/genomicdistributions/paper.svg" height="25" class="bullet">Lawson et al. (2020). <i>Genome Biology</i>.</span>
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# Methods in computational epigenetics

Nathan Sheffield

<span style="font-size:0.6em"><a href="http://www.databio.org/slides">www.databio.org/slides</a></span>

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@title

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@cocoa

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## Acknowledgments

**Collaborators**
- Fran Garrett-Bakelman
- Stefan Bekiranov

</div>

**Sheffield lab**
- **John Lawson**
- **Jason Smith**
- Jianglin Feng
- Michal Stolarczyk
- Kristyna Kupkova
- Aaron Gu
- Jose Verdezoto
- Tessa Danehy

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**Funding:**

UVA Cancer Center

</div>
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## Acknowledgments

**Collaborators**
- Fran Garrett-Bakelman
- Stefan Bekiranov

</div>

**Sheffield lab**
- **John Lawson**
- **Jason Smith**
- Jianglin Feng
- Michal Stolarczyk
- Kristyna Kupkova
- Aaron Gu
- Jose Verdezoto
- Tessa Danehy

</div>

**Funding:**

UVA Cancer Center

</div>
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## Acknowledgments

**Collaborators**
<br>Vince Reuter
<br>Andre Rendeiro
<br>Levi Waldron

<br><br>
**Alumni**
<br>Aaron Gu
<br>Jianglin Feng
<br>Ognen Duzlevski
<br>Tessa Danehy
</div>

**Sheffield lab**
<br>Erfaneh Gharavi
<br>Michal Stolarczyk
<br>John Lawson
<br>Jason Smith
<br>Kristyna Kupkova
<br>John Stubbs
<br>Bingjie Xue
<br>Jose Verdezoto
<br>Nathan LeRoy
<br>Oleksandr Khoroshevskyi
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<div class="col3" style="font-size:.6em">
<b>Funding:</b><br>
<br><img src="/_modules/ack-generic/University_of_Virginia_Rotunda_logo.svg" height="40"><img src="/_modules/ack-generic/University_of_Virginia_logo_white.svg" height="40">
<br><img src="/_modules/ack-generic/NIH_logo_black.svg" height="80"><br>NIGMS R35-GM128636
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# Thank You

<span class="small bullet"><img src="/images/external/github_bug_black.svg" height="20" class="bullet"><a href="http://github.com/nsheff">nsheff</a></span> &middot;
<span class="small bullet"><img src="/images/icons/web.svg" height="25" class="bullet"><a href="http://databio.org">databio.org</a></span> &middot;
<span class="small bullet"><img src="/images/icons/letter.svg" height="25" class="bullet"><a href="mailto:nsheffield@virginia.edu">nsheffield@virginia.edu</a></span>

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