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DNA Methylation introduction section #956

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merged 35 commits into from
Aug 1, 2019
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brockclarke
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final draft of introduction to the DNA methylation section here. There's a nice review on methylation age clocks to potentially cite that will be in press at genome biology likely in a few weeks

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cgreene commented Jul 18, 2019

final draft of introduction to the DNA methylation section here. There's a nice review on methylation age clocks to potentially cite that will be in press at genome biology likely in a few weeks

Not sure if you want to update for this, but I'm reminding here in case it has come out in the meantime.

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A few minor things. The largest comments center on helping a computer scientist / ML researcher get to relevant literature quickly by adding a few citations. I'm happy to quickly re-review and merge after you take a look. Thanks!


DNA Methylation (DNAm), is the process of adding a methyl group to a cytosine in the context of a CpG dinucleotide.
This DNA-level epigenetic modification regulates gene transcription, is critical in development, and alterations to DNA methylation are well-established as contributing to pathophysiology of many diseases including cancers.
Studies of DNA methylation have also shed light on the processes involving initial differentiation of stem cells, aging and pathogenesis in response to environmental exposures.
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References would help here, again - over-reference the bio side to help ML people get to relevant literature quickly.

This DNA-level epigenetic modification regulates gene transcription, is critical in development, and alterations to DNA methylation are well-established as contributing to pathophysiology of many diseases including cancers.
Studies of DNA methylation have also shed light on the processes involving initial differentiation of stem cells, aging and pathogenesis in response to environmental exposures.

Traditional analytic approaches to DNA methylation data often focus on estimating differential DNA methylation between groups or related with an outcome using linear mixed effects models.
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add a ref or two

Studies of DNA methylation have also shed light on the processes involving initial differentiation of stem cells, aging and pathogenesis in response to environmental exposures.

Traditional analytic approaches to DNA methylation data often focus on estimating differential DNA methylation between groups or related with an outcome using linear mixed effects models.
In addition, a growing application of DNA methylation measures is to infer cellular or subject phenotypes from samples and either examine the relation of these phenotypes with outcomes or disease states directly, and/or include them in models as covariates.
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another ref or two for examples

Importantly, reference DNA methylation profiles of leukocytes are available to infer immune cell type proportions with measures of DNA methylation in peripheral blood DNA [@tag:Houseman2012],[@tag:Salas2018], a novel approach to immunophenotyping that only requires.
Cell type inference is important for adjusting for cell-type composition in epigenome-wide association studies [@tag:Teschendorff2017].
While utilizing reference-based libraries demonstrates strong predictive value for immune cell type estimation, these methods severely restrict the amount of underlying biology that can be understood and correlated with disease manifestations and phenotypes. When a referenced-based library is not available for use, unsupervised methods are able to estimate these immune profiles [@tag:Titus2017].
Methods that do not rely on these reference libraries [@tag:Houseman2016], are limited by being unable to fully capture the nonlinearity of the methylation data.
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Suggested change
Methods that do not rely on these reference libraries [@tag:Houseman2016], are limited by being unable to fully capture the nonlinearity of the methylation data.
However, methods that do not rely on reference libraries [@tag:Houseman2016] are unable to fully capture the nonlinearity of methylation data.

I think I understood this correctly. Check before committing the suggestion 😁

@jlevy44 jlevy44 mentioned this pull request Jul 22, 2019
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@brockclarke
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final draft of introduction to the DNA methylation section here. There's a nice review on methylation age clocks to potentially cite that will be in press at genome biology likely in a few weeks

Not sure if you want to update for this, but I'm reminding here in case it has come out in the meantime.

not out yet unfortunately..

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cgreene commented Jul 23, 2019

I'm guessing you didn't mean to close the PR. Reopening.

@cgreene cgreene reopened this Jul 23, 2019
brockclarke and others added 5 commits July 26, 2019 09:23
Co-Authored-By: Casey Greene <[email protected]>
Co-Authored-By: Casey Greene <[email protected]>
Co-Authored-By: Casey Greene <[email protected]>
Co-Authored-By: Casey Greene <[email protected]>
Co-Authored-By: Casey Greene <[email protected]>
@@ -47,6 +47,28 @@ Deep learning applied to gene expression data is still in its infancy, but the f
Many previously untestable hypotheses can now be interrogated as deep learning enables analysis of increasing amounts of data generated by new technologies.
For example, the effects of cellular heterogeneity on basic biology and disease etiology can now be explored by single-cell RNA-seq and high-throughput fluorescence-based imaging, techniques we discuss below that will benefit immensely from deep learning approaches.

### DNA Methylation
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Suggested change
### DNA Methylation
### DNA methylation

With the change coming in from @agitter ths will line up the headers.

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cgreene commented Jul 28, 2019

I think there are still a few things to correct. I resolved the merge conflicts. Tag me when you are ready for a re-review!

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cgreene commented Jul 31, 2019

Let me know when you want me to take another look - it seems you are addressing the comments now 👍

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Let me know when you want me to take another look - it seems you are addressing the comments now 👍

I have addressed the comments and added refs. etc. you can take a look whenever you can! thanks

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A few more minor changes. After these go in I'll merge - thanks!

brockclarke and others added 2 commits July 31, 2019 16:08
Co-Authored-By: Casey Greene <[email protected]>
Co-Authored-By: Casey Greene <[email protected]>
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I think these refs got lost on a merge. Can you add them back to fix the build?

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agitter commented Aug 1, 2019

The build failed because there are missing tag definitions:

## ERROR
CSL JSON Data retrieval failed for:
tag:Levy-Jurgenson2018
tag:Levy2019
tag:Momeni2018
tag:Ni2018
tag:Roberston2005

The tag file does have Robertson2005, is that what tag:Roberston2005 should match?

correcting spelling error for Roberston
@brockclarke
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The build failed because there are missing tag definitions:

## ERROR
CSL JSON Data retrieval failed for:
tag:Levy-Jurgenson2018
tag:Levy2019
tag:Momeni2018
tag:Ni2018
tag:Roberston2005

The tag file does have Robertson2005, is that what tag:Roberston2005 should match?

Robertson2005 doi:10.1038/nrg1655
pushed spelling error correction

@brockclarke
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The build failed because there are missing tag definitions:

## ERROR
CSL JSON Data retrieval failed for:
tag:Levy-Jurgenson2018
tag:Levy2019
tag:Momeni2018
tag:Ni2018
tag:Roberston2005

The tag file does have Robertson2005, is that what tag:Roberston2005 should match?

Robertson2005 doi:10.1038/nrg1655
pushed spelling error correction

also, > > tag:Levy-Jurgenson2018

tag:Levy2019
tag:Momeni2018
tag:Ni2018 are in jlevy44's section

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agitter commented Aug 1, 2019

@brockclarke can you please commit the rest of @cgreene's suggestions? We don't have the ability to directly commit to this pull request branch. His edits should fix the rest of the deleted tags.

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Approving based on the build passing and the extra files being removed from the pull request. I didn't review the content in full. I'll likely make a separate minor pull request for stylistic changes after we merge this.

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agitter commented Aug 1, 2019

Please disregard my detailed comments on specific lines above. I was going to make style suggestions in this pull request but now think that should be done separately.

@cgreene cgreene merged commit 7813077 into greenelab:master Aug 1, 2019
dhimmel pushed a commit that referenced this pull request Aug 1, 2019
This build is based on
7813077.

This commit was created by the following Travis CI build and job:
https://travis-ci.org/greenelab/deep-review/builds/566537173
https://travis-ci.org/greenelab/deep-review/jobs/566537174

[ci skip]

The full commit message that triggered this build is copied below:

DNA Methylation introduction section (#956)

* First few edits

* final draft

* Update citation-tags.tsv

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* changes in response to review here

added refs and revised some language

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update 04.study.md

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Anthony Gitter <[email protected]>

* delete Rhistory

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Restore webpage files

* Update 04.study.md

correcting spelling error for Roberston

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>
dhimmel pushed a commit that referenced this pull request Aug 1, 2019
This build is based on
7813077.

This commit was created by the following Travis CI build and job:
https://travis-ci.org/greenelab/deep-review/builds/566537173
https://travis-ci.org/greenelab/deep-review/jobs/566537174

[ci skip]

The full commit message that triggered this build is copied below:

DNA Methylation introduction section (#956)

* First few edits

* final draft

* Update citation-tags.tsv

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* changes in response to review here

added refs and revised some language

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update content/04.study.md

Co-Authored-By: Casey Greene <[email protected]>

* Update 04.study.md

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Anthony Gitter <[email protected]>

* delete Rhistory

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Restore webpage files

* Update 04.study.md

correcting spelling error for Roberston

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>

* Update content/citation-tags.tsv

Co-Authored-By: Casey Greene <[email protected]>
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4 participants