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@@ -29,6 +29,9 @@
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% Allow landscape pages
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% Allow landscape pages
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\usepackage{pdflscape}
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\usepackage{pdflscape}
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+% Allow doing things after the end of the current page
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+% (to avoid landscape figures breaking up text)
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+\usepackage{afterpage}
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% This one breaks subfigs so it's disabled
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% This one breaks subfigs so it's disabled
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% https://tex.stackexchange.com/questions/65680/automatically-bold-first-sentence-of-a-floats-caption
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% https://tex.stackexchange.com/questions/65680/automatically-bold-first-sentence-of-a-floats-caption
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@@ -57,7 +60,7 @@ todonotes
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\graphics default
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\graphics default
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\default_output_format pdf4
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\default_output_format pdf4
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\output_sync 0
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\output_sync 0
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-\bibtex_command default
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+\bibtex_command biber
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\index_command default
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\index_command default
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\paperfontsize 12
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\paperfontsize 12
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\spacing double
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\spacing double
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@@ -83,9 +86,11 @@ todonotes
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\use_package stackrel 1
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\use_package stackrel 1
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\use_package stmaryrd 1
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\use_package stmaryrd 1
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\use_package undertilde 1
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\use_package undertilde 1
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-\cite_engine basic
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-\cite_engine_type default
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+\cite_engine biblatex
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+\cite_engine_type authoryear
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\biblio_style plain
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\biblio_style plain
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+\biblatex_bibstyle authoryear
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+\biblatex_citestyle numeric
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\use_bibtopic false
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\use_bibtopic false
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\use_indices false
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\use_indices false
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\paperorientation portrait
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\paperorientation portrait
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@@ -251,6 +256,43 @@ On final pass: Check all figures to make sure they fit on the page with
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Abstract
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Abstract
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\end_layout
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\end_layout
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+\begin_layout Standard
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+\begin_inset Note Note
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+status open
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+
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+\begin_layout Plain Layout
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+It is included as an integral part of the thesis and should immediately
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+ precede the introduction.
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+\end_layout
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+
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+\begin_layout Plain Layout
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+Preparing your Abstract.
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+ Your abstract (a succinct description of your work) is limited to 350 words.
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+ UMI will shorten it if they must; please do not exceed the limit.
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+\end_layout
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+
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+\begin_layout Itemize
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+Include pertinent place names, names of persons (in full), and other proper
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+ nouns.
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+ These are useful in automated retrieval.
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+\end_layout
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+
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+\begin_layout Itemize
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+Display symbols, as well as foreign words and phrases, clearly and accurately.
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+ Include transliterations for characters other than Roman and Greek letters
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+ and Arabic numerals.
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+ Include accents and diacritical marks.
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+\end_layout
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+
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+\begin_layout Itemize
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+Do not include graphs, charts, tables, or illustrations in your abstract.
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+\end_layout
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+
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+\end_inset
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+
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+
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+\end_layout
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+
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\begin_layout Chapter
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\begin_layout Chapter
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Introduction
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Introduction
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\end_layout
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\end_layout
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@@ -982,7 +1024,7 @@ RNA-seq has a large confounding batch effect
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\begin_inset Float figure
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\begin_inset Float figure
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wide false
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wide false
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sideways false
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sideways false
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-status collapsed
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+status open
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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\begin_inset Flex TODO Note (inline)
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\begin_inset Flex TODO Note (inline)
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@@ -1805,7 +1847,14 @@ MOFA recovers biologically relevant variation from blind analysis by correlating
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\begin_layout Standard
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\begin_layout Standard
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\begin_inset ERT
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\begin_inset ERT
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-status collapsed
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+status open
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+
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+\begin_layout Plain Layout
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+
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+
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+\backslash
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+afterpage{
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+\end_layout
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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@@ -1960,7 +2009,7 @@ MOFA latent factors separate technical confounders from
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\begin_layout Standard
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\begin_layout Standard
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\begin_inset ERT
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\begin_inset ERT
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-status collapsed
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+status open
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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@@ -1969,6 +2018,11 @@ status collapsed
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end{landscape}
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end{landscape}
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\end_layout
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\end_layout
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+\begin_layout Plain Layout
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+
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+}
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+\end_layout
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+
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\end_inset
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\end_inset
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@@ -2923,507 +2977,215 @@ RNA-seq and H3K4 methylation patterns in naive and memory show convergence
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\end_layout
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\end_layout
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\begin_layout Standard
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\begin_layout Standard
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-\begin_inset Float figure
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-placement p
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-wide false
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-sideways false
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-status open
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-
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-\begin_layout Plain Layout
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-\align center
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-\begin_inset Float figure
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-wide false
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-sideways false
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-status collapsed
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-
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-\begin_layout Plain Layout
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-\align center
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-\begin_inset Graphics
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- filename graphics/CD4-csaw/ChIP-seq/H3K4me2-promoter-PCA-group-CROP.png
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- lyxscale 25
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- width 45col%
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- groupId pcoa-prom-subfig
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-
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-\end_inset
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-
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\end_layout
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\end_layout
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-\begin_layout Plain Layout
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-\begin_inset Caption Standard
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+\begin_layout Standard
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+\begin_inset ERT
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+status open
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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-\series bold
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-\begin_inset CommandInset label
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-LatexCommand label
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-name "fig:PCoA-H3K4me2-prom"
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-
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-\end_inset
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-PCoA plot of H3K4me2 promoters, after subtracting surrogate variables
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+\backslash
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+afterpage{
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\end_layout
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\end_layout
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-\end_inset
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+\begin_layout Plain Layout
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+\backslash
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+begin{landscape}
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\end_layout
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\end_layout
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\end_inset
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\end_inset
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-\begin_inset space \hfill{}
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-\end_inset
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-
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+\end_layout
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-\begin_inset Float figure
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+\begin_layout Standard
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+\begin_inset Float table
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wide false
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wide false
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sideways false
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sideways false
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status collapsed
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status collapsed
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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\align center
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\align center
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-\begin_inset Graphics
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- filename graphics/CD4-csaw/ChIP-seq/H3K4me3-promoter-PCA-group-CROP.png
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- lyxscale 25
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- width 45col%
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- groupId pcoa-prom-subfig
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-
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-\end_inset
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-
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-
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-\end_layout
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-
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-\begin_layout Plain Layout
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-\begin_inset Caption Standard
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+\begin_inset Tabular
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+<lyxtabular version="3" rows="6" columns="7">
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+<features tabularvalignment="middle">
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+<column alignment="center" valignment="top">
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+<column alignment="center" valignment="top">
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+<column alignment="center" valignment="top">
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+<column alignment="center" valignment="top">
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+<column alignment="center" valignment="top">
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+<column alignment="center" valignment="top">
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+<column alignment="center" valignment="top">
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+<row>
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+<cell alignment="center" valignment="top" usebox="none">
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+\begin_inset Text
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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-\series bold
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-\begin_inset CommandInset label
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-LatexCommand label
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-name "fig:PCoA-H3K4me3-prom"
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+\end_layout
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\end_inset
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\end_inset
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+</cell>
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+<cell multicolumn="1" alignment="center" valignment="top" topline="true" leftline="true" rightline="true" usebox="none">
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+\begin_inset Text
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-PCoA plot of H3K4me3 promoters, after subtracting surrogate variables
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+\begin_layout Plain Layout
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+Number of significant promoters
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\end_layout
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\end_layout
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\end_inset
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\end_inset
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+</cell>
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+<cell multicolumn="2" alignment="center" valignment="top" topline="true" leftline="true" usebox="none">
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+\begin_inset Text
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+\begin_layout Plain Layout
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\end_layout
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\end_layout
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\end_inset
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\end_inset
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+</cell>
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+<cell multicolumn="2" alignment="center" valignment="top" topline="true" leftline="true" rightline="true" usebox="none">
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+\begin_inset Text
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+\begin_layout Plain Layout
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\end_layout
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\end_layout
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-\begin_layout Plain Layout
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-\align center
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-\begin_inset Float figure
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-wide false
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-sideways false
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-status collapsed
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+\end_inset
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+</cell>
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+<cell multicolumn="1" alignment="center" valignment="top" topline="true" leftline="true" rightline="true" usebox="none">
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+\begin_inset Text
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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-\align center
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-\begin_inset Graphics
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- filename graphics/CD4-csaw/ChIP-seq/H3K27me3-promoter-PCA-group-CROP.png
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- lyxscale 25
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- width 45col%
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- groupId pcoa-prom-subfig
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+Est.
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+ differentially modified promoters
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+\end_layout
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\end_inset
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\end_inset
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+</cell>
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+<cell multicolumn="2" alignment="center" valignment="top" topline="true" leftline="true" usebox="none">
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+\begin_inset Text
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+\begin_layout Plain Layout
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\end_layout
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\end_layout
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-\begin_layout Plain Layout
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-\begin_inset Caption Standard
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+\end_inset
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+</cell>
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+<cell multicolumn="2" alignment="center" valignment="top" topline="true" leftline="true" rightline="true" usebox="none">
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+\begin_inset Text
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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-\series bold
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-\begin_inset CommandInset label
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-LatexCommand label
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-name "fig:PCoA-H3K27me3-prom"
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+\end_layout
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\end_inset
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\end_inset
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+</cell>
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+</row>
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+<row>
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+<cell alignment="center" valignment="top" topline="true" bottomline="true" leftline="true" usebox="none">
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+\begin_inset Text
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-PCoA plot of H3K27me3 promoters, after subtracting surrogate variables
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+\begin_layout Plain Layout
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+Time Point
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\end_layout
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\end_layout
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\end_inset
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\end_inset
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+</cell>
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+<cell alignment="center" valignment="top" topline="true" bottomline="true" leftline="true" usebox="none">
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+\begin_inset Text
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-
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+\begin_layout Plain Layout
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+H3K4me2
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\end_layout
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\end_layout
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\end_inset
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\end_inset
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+</cell>
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+<cell alignment="center" valignment="top" topline="true" bottomline="true" leftline="true" usebox="none">
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+\begin_inset Text
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+\begin_layout Plain Layout
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+H3K4me3
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+\end_layout
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-\begin_inset space \hfill{}
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\end_inset
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\end_inset
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+</cell>
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+<cell alignment="center" valignment="top" topline="true" bottomline="true" leftline="true" rightline="true" usebox="none">
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+\begin_inset Text
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+\begin_layout Plain Layout
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+H3K27me3
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+\end_layout
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-\begin_inset Float figure
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-wide false
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-sideways false
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-status collapsed
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+\end_inset
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+</cell>
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+<cell alignment="center" valignment="top" topline="true" bottomline="true" leftline="true" usebox="none">
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+\begin_inset Text
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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-\align center
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-\begin_inset Graphics
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- filename graphics/CD4-csaw/RNA-seq/PCA-final-23-CROP.png
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- lyxscale 25
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- width 45col%
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- groupId pcoa-prom-subfig
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+H3K4me2
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+\end_layout
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\end_inset
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\end_inset
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+</cell>
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+<cell alignment="center" valignment="top" topline="true" bottomline="true" leftline="true" usebox="none">
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+\begin_inset Text
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-
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+\begin_layout Plain Layout
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+H3K4me3
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\end_layout
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\end_layout
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-\begin_layout Plain Layout
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-\begin_inset Caption Standard
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+\end_inset
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+</cell>
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+<cell alignment="center" valignment="top" topline="true" bottomline="true" leftline="true" rightline="true" usebox="none">
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+\begin_inset Text
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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-
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-\series bold
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-\begin_inset CommandInset label
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- This is consistent with the counts of significantly differentially modified
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- 3 histone marks and RNA expression for naive and memory cells are most
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- similar at day 14, the furthest time point after activation.
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@@ -3697,19 +3459,312 @@ literal "false"
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|
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|
+ filename graphics/CD4-csaw/ChIP-seq/H3K4me2-promoter-PCA-group-CROP.png
|
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+ lyxscale 25
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|
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|
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|
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+
|
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|
+\end_inset
|
|
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+
|
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|
+PCoA plot of H3K4me2 promoters, after subtracting surrogate variables
|
|
|
|
+\end_layout
|
|
|
|
+
|
|
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|
+\end_inset
|
|
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|
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|
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|
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+\begin_layout Plain Layout
|
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+\align center
|
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+\begin_inset Graphics
|
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+ filename graphics/CD4-csaw/ChIP-seq/H3K4me3-promoter-PCA-group-CROP.png
|
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+ lyxscale 25
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+ width 45col%
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|
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|
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|
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+\begin_layout Plain Layout
|
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+name "fig:PCoA-H3K4me3-prom"
|
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+
|
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+\end_inset
|
|
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|
+
|
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|
+PCoA plot of H3K4me3 promoters, after subtracting surrogate variables
|
|
|
|
+\end_layout
|
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|
|
+
|
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|
+\end_inset
|
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|
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+\end_layout
|
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+\begin_layout Plain Layout
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+\align center
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+wide false
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+
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+\begin_layout Plain Layout
|
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+\align center
|
|
|
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+\begin_inset Graphics
|
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+ filename graphics/CD4-csaw/ChIP-seq/H3K27me3-promoter-PCA-group-CROP.png
|
|
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|
+ lyxscale 25
|
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|
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+ width 45col%
|
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+ groupId pcoa-prom-subfig
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+
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|
+\end_inset
|
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+
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+
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+\end_layout
|
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+
|
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|
+\begin_layout Plain Layout
|
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+\begin_inset Caption Standard
|
|
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+
|
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|
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+\begin_layout Plain Layout
|
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+
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+\series bold
|
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+\begin_inset CommandInset label
|
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+LatexCommand label
|
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+name "fig:PCoA-H3K27me3-prom"
|
|
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|
+
|
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|
+\end_inset
|
|
|
|
+
|
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|
|
+PCoA plot of H3K27me3 promoters, after subtracting surrogate variables
|
|
|
|
+\end_layout
|
|
|
|
+
|
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|
|
+\end_inset
|
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+
|
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+
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|
+\end_layout
|
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+
|
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|
+\end_inset
|
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+
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+
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|
+\begin_inset space \hfill{}
|
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|
+\end_inset
|
|
|
|
+
|
|
|
|
+
|
|
|
|
+\begin_inset Float figure
|
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|
|
+wide false
|
|
|
|
+sideways false
|
|
|
|
+status collapsed
|
|
|
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+
|
|
|
|
+\begin_layout Plain Layout
|
|
|
|
+\align center
|
|
|
|
+\begin_inset Graphics
|
|
|
|
+ filename graphics/CD4-csaw/RNA-seq/PCA-final-23-CROP.png
|
|
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|
+ lyxscale 25
|
|
|
|
+ width 45col%
|
|
|
|
+ groupId pcoa-prom-subfig
|
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|
+
|
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|
+\end_inset
|
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+
|
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+
|
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|
+\end_layout
|
|
|
|
+
|
|
|
|
+\begin_layout Plain Layout
|
|
|
|
+\begin_inset Caption Standard
|
|
|
|
+
|
|
|
|
+\begin_layout Plain Layout
|
|
|
|
+
|
|
|
|
+\series bold
|
|
|
|
+\begin_inset CommandInset label
|
|
|
|
+LatexCommand label
|
|
|
|
+name "fig:RNA-PCA-group"
|
|
|
|
+
|
|
|
|
+\end_inset
|
|
|
|
+
|
|
|
|
+RNA-seq PCoA showing principal coordiantes 2 and 3.
|
|
|
|
+\end_layout
|
|
|
|
+
|
|
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|
+\end_inset
|
|
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+
|
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|
+
|
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|
+\end_layout
|
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+
|
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|
+\end_inset
|
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+
|
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|
+
|
|
|
|
+\end_layout
|
|
|
|
+
|
|
|
|
+\begin_layout Plain Layout
|
|
|
|
+\begin_inset Caption Standard
|
|
|
|
+
|
|
|
|
+\begin_layout Plain Layout
|
|
|
|
+
|
|
|
|
+\series bold
|
|
|
|
+\begin_inset CommandInset label
|
|
|
|
+LatexCommand label
|
|
|
|
+name "fig:PCoA-promoters"
|
|
|
|
+
|
|
|
|
+\end_inset
|
|
|
|
+
|
|
|
|
+PCoA plots for promoter ChIP-seq and expression RNA-seq data
|
|
|
|
+\end_layout
|
|
|
|
+
|
|
|
|
+\end_inset
|
|
|
|
+
|
|
|
|
+
|
|
|
|
+\end_layout
|
|
|
|
+
|
|
|
|
+\end_inset
|
|
|
|
+
|
|
|
|
+
|
|
|
|
+\end_layout
|
|
|
|
+
|
|
|
|
+\begin_layout Standard
|
|
|
|
+\begin_inset Flex TODO Note (inline)
|
|
|
|
+status open
|
|
|
|
+
|
|
|
|
+\begin_layout Plain Layout
|
|
|
|
+Check up on figure refs in this paragraph
|
|
|
|
+\end_layout
|
|
|
|
+
|
|
|
|
+\end_inset
|
|
|
|
+
|
|
|
|
+
|
|
|
|
+\end_layout
|
|
|
|
+
|
|
|
|
+\begin_layout Standard
|
|
|
|
+Figure
|
|
|
|
+\begin_inset CommandInset ref
|
|
|
|
+LatexCommand ref
|
|
|
|
+reference "fig:PCoA-promoters"
|
|
|
|
+plural "false"
|
|
|
|
+caps "false"
|
|
|
|
+noprefix "false"
|
|
|
|
|
|
-\begin_layout Plain Layout
|
|
|
|
|
|
+\end_inset
|
|
|
|
|
|
|
|
+ shows the patterns of variation in all 3 histone marks in the promoter
|
|
|
|
+ regions of the genome using principal coordinate analysis.
|
|
|
|
+ All 3 marks show a noticeable convergence between the naive and memory
|
|
|
|
+ samples at day 14, visible as an overlapping of the day 14 groups on each
|
|
|
|
+ plot.
|
|
|
|
+ This is consistent with the counts of significantly differentially modified
|
|
|
|
+ promoters and estimates of the total numbers of differentially modified
|
|
|
|
+ promoters shown in Table
|
|
|
|
+\begin_inset CommandInset ref
|
|
|
|
+LatexCommand ref
|
|
|
|
+reference "tab:Number-signif-promoters"
|
|
|
|
+plural "false"
|
|
|
|
+caps "false"
|
|
|
|
+noprefix "false"
|
|
|
|
|
|
-\backslash
|
|
|
|
-end{landscape}
|
|
|
|
-\end_layout
|
|
|
|
|
|
+\end_inset
|
|
|
|
+
|
|
|
|
+.
|
|
|
|
+ For all histone marks, evidence of differential modification between naive
|
|
|
|
+ and memory samples was detected at every time point except day 14.
|
|
|
|
+ The day 14 convergence pattern is also present in the RNA-seq data (Figure
|
|
|
|
+
|
|
|
|
+\begin_inset CommandInset ref
|
|
|
|
+LatexCommand ref
|
|
|
|
+reference "fig:RNA-PCA-group"
|
|
|
|
+plural "false"
|
|
|
|
+caps "false"
|
|
|
|
+noprefix "false"
|
|
|
|
|
|
\end_inset
|
|
\end_inset
|
|
|
|
|
|
|
|
+), albiet in the 2nd and 3rd principal coordinates, indicating that it is
|
|
|
|
+ not the most dominant pattern driving gene expression.
|
|
|
|
+ Taken together, the data show that promoter histone methylation for these
|
|
|
|
+ 3 histone marks and RNA expression for naive and memory cells are most
|
|
|
|
+ similar at day 14, the furthest time point after activation.
|
|
|
|
+ MOFA was also able to capture this day 14 convergence pattern in latent
|
|
|
|
+ factor 5 (Figure
|
|
|
|
+\begin_inset CommandInset ref
|
|
|
|
+LatexCommand ref
|
|
|
|
+reference "fig:mofa-lf-scatter"
|
|
|
|
+plural "false"
|
|
|
|
+caps "false"
|
|
|
|
+noprefix "false"
|
|
|
|
+
|
|
|
|
+\end_inset
|
|
|
|
|
|
|
|
+), which accounts for shared variation across all 3 histone marks and the
|
|
|
|
+ RNA-seq data, confirming that this is a coordinated pattern across all
|
|
|
|
+ 4 data sets.
|
|
\end_layout
|
|
\end_layout
|
|
|
|
|
|
\begin_layout Subsection
|
|
\begin_layout Subsection
|
|
@@ -3733,7 +3788,14 @@ For the figures in this section, the group labels are arbitrary, so if time
|
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\begin_layout Standard
|
|
\begin_layout Standard
|
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\begin_inset ERT
|
|
\begin_inset ERT
|
|
-status collapsed
|
|
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+status open
|
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+
|
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|
+\begin_layout Plain Layout
|
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+
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+
|
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|
+\backslash
|
|
|
|
+afterpage{
|
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|
+\end_layout
|
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\begin_layout Plain Layout
|
|
\begin_layout Plain Layout
|
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@@ -4164,7 +4226,7 @@ shape
|
|
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|
\begin_layout Standard
|
|
\begin_layout Standard
|
|
\begin_inset ERT
|
|
\begin_inset ERT
|
|
-status collapsed
|
|
|
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|
+status open
|
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\begin_layout Plain Layout
|
|
\begin_layout Plain Layout
|
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|
@@ -4173,6 +4235,11 @@ status collapsed
|
|
end{landscape}
|
|
end{landscape}
|
|
\end_layout
|
|
\end_layout
|
|
|
|
|
|
|
|
+\begin_layout Plain Layout
|
|
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+
|
|
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|
+}
|
|
|
|
+\end_layout
|
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+
|
|
\end_inset
|
|
\end_inset
|
|
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|
@@ -4245,7 +4312,7 @@ status collapsed
|
|
\begin_inset Graphics
|
|
\begin_inset Graphics
|
|
filename graphics/CD4-csaw/LaMere2016_fig8.pdf
|
|
filename graphics/CD4-csaw/LaMere2016_fig8.pdf
|
|
lyxscale 50
|
|
lyxscale 50
|
|
- width 50col%
|
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+ width 100col%
|
|
groupId colwidth
|
|
groupId colwidth
|
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\end_inset
|
|
\end_inset
|
|
@@ -4326,7 +4393,14 @@ Workflow
|
|
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|
\begin_layout Standard
|
|
\begin_layout Standard
|
|
\begin_inset ERT
|
|
\begin_inset ERT
|
|
-status collapsed
|
|
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+status open
|
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+
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+\begin_layout Plain Layout
|
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+
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+
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+\backslash
|
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|
+afterpage{
|
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+\end_layout
|
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\begin_layout Plain Layout
|
|
\begin_layout Plain Layout
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@@ -4386,7 +4460,7 @@ Dependency graph of steps in reproducible workflow
|
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\begin_layout Standard
|
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\begin_layout Standard
|
|
\begin_inset ERT
|
|
\begin_inset ERT
|
|
-status collapsed
|
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+status open
|
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|
\begin_layout Plain Layout
|
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\begin_layout Plain Layout
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@@ -4395,6 +4469,11 @@ status collapsed
|
|
end{landscape}
|
|
end{landscape}
|
|
\end_layout
|
|
\end_layout
|
|
|
|
|
|
|
|
+\begin_layout Plain Layout
|
|
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|
+
|
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|
+}
|
|
|
|
+\end_layout
|
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+
|
|
\end_inset
|
|
\end_inset
|
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|
@@ -4644,7 +4723,7 @@ status collapsed
|
|
\begin_inset Graphics
|
|
\begin_inset Graphics
|
|
filename graphics/methylvoom/sigmoid.pdf
|
|
filename graphics/methylvoom/sigmoid.pdf
|
|
lyxscale 50
|
|
lyxscale 50
|
|
- width 50col%
|
|
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|
+ width 100col%
|
|
groupId colwidth
|
|
groupId colwidth
|
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\end_inset
|
|
\end_inset
|
|
@@ -5491,7 +5570,7 @@ status collapsed
|
|
\begin_inset Graphics
|
|
\begin_inset Graphics
|
|
filename graphics/PAM/predplot.pdf
|
|
filename graphics/PAM/predplot.pdf
|
|
lyxscale 50
|
|
lyxscale 50
|
|
- width 50col%
|
|
|
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|
+ width 100col%
|
|
groupId colwidth
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|
groupId colwidth
|
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|
\end_inset
|
|
\end_inset
|
|
@@ -5562,6 +5641,13 @@ fRMA and SCAN achieve maintain classification performance while eliminating
|
|
|
|
|
|
\begin_layout Standard
|
|
\begin_layout Standard
|
|
\begin_inset Float figure
|
|
\begin_inset Float figure
|
|
|
|
+wide false
|
|
|
|
+sideways false
|
|
|
|
+status open
|
|
|
|
+
|
|
|
|
+\begin_layout Plain Layout
|
|
|
|
+\align center
|
|
|
|
+\begin_inset Float figure
|
|
placement tb
|
|
placement tb
|
|
wide false
|
|
wide false
|
|
sideways false
|
|
sideways false
|
|
@@ -5572,8 +5658,75 @@ status collapsed
|
|
\begin_inset Graphics
|
|
\begin_inset Graphics
|
|
filename graphics/PAM/ROC-TXvsAR-internal.pdf
|
|
filename graphics/PAM/ROC-TXvsAR-internal.pdf
|
|
lyxscale 50
|
|
lyxscale 50
|
|
- width 50col%
|
|
|
|
- groupId colwidth
|
|
|
|
|
|
+ height 40theight%
|
|
|
|
+ groupId roc-pam
|
|
|
|
+
|
|
|
|
+\end_inset
|
|
|
|
+
|
|
|
|
+
|
|
|
|
+\end_layout
|
|
|
|
+
|
|
|
|
+\begin_layout Plain Layout
|
|
|
|
+\begin_inset Caption Standard
|
|
|
|
+
|
|
|
|
+\begin_layout Plain Layout
|
|
|
|
+\begin_inset CommandInset label
|
|
|
|
+LatexCommand label
|
|
|
|
+name "fig:ROC-PAM-int"
|
|
|
|
+
|
|
|
|
+\end_inset
|
|
|
|
+
|
|
|
|
+ROC curves for PAM on internal validation data
|
|
|
|
+\end_layout
|
|
|
|
+
|
|
|
|
+\end_inset
|
|
|
|
+
|
|
|
|
+
|
|
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+ lyxscale 50
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@@ -5588,12 +5741,11 @@ status collapsed
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-name "fig:ROC-PAM-int"
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-ROC curves for PAM on internal validation data using different normalization
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- strategies
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+ROC curves for PAM using different normalization strategies
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@@ -6219,52 +6371,6 @@ noprefix "false"
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more jagged appearance.
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more jagged appearance.
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\begin_layout Standard
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\begin_layout Standard
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For external validation, as expected, all the AUC values are lower than
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For external validation, as expected, all the AUC values are lower than
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the internal validations, ranging from 0.642 to 0.750 (Table
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the internal validations, ranging from 0.642 to 0.750 (Table
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@@ -6309,7 +6415,7 @@ fRMA with custom-generated vectors enables normalization on hthgu133pluspm
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@@ -6980,6 +7086,13 @@ status open
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@@ -7048,7 +7161,6 @@ name "fig:meanvar-basic"
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Mean-variance trend for analysis A.
|
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Mean-variance trend for analysis A.
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-
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@@ -7166,7 +7278,6 @@ The log2(standard deviation) for each probe is plotted against the probe's
|
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Density of points is also indicated by the dark blue contour lines.
|
|
Density of points is also indicated by the dark blue contour lines.
|
|
The prior variance trend estimated by eBayes is shown in light blue, while
|
|
The prior variance trend estimated by eBayes is shown in light blue, while
|
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the lowess trend of the points is shown in red.
|
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the lowess trend of the points is shown in red.
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-
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@@ -7534,7 +7650,7 @@ status collapsed
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|
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filename graphics/methylvoom/unadj.dupcor.sva.voomaw/sample-weights-PAGE3-CROP.pdf
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-), and the mean-variance trend is modeled by scaling the probe's estimated
|
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|
- variance for each observation using the weights computed by voom.
|
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- The difference between these two methods is analogous to the difference
|
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- between a t-test with equal variance and a t-test with unequal variance,
|
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|
- except that the unequal group variances used in the latter test are estimated
|
|
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+), indicating that the mean-variance trend is adequately modeled by scaling
|
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+ the estimated variance for each observation using the weights computed
|
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+ by voom.
|
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+
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+\end_layout
|
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+
|
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+\begin_layout Standard
|
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|
+The difference between the standard empirical Bayes trended variance modeling
|
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|
+ (analysis B) and voom (analysis C) is analogous to the difference between
|
|
|
|
+ a t-test with equal variance and a t-test with unequal variance, except
|
|
|
|
+ that the unequal group variances used in the latter test are estimated
|
|
based on the mean-variance trend from all the probes rather than the data
|
|
based on the mean-variance trend from all the probes rather than the data
|
|
for the specific probe being tested, thus stabilizing the group variance
|
|
for the specific probe being tested, thus stabilizing the group variance
|
|
estimates by sharing information between probes.
|
|
estimates by sharing information between probes.
|
|
- In practice, allowing voom to model the variance using observation weights
|
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- in this manner allows the linear model fit to concentrate statistical power
|
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- where it will do the most good.
|
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+ Allowing voom to model the variance using observation weights in this manner
|
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+ allows the linear model fit to concentrate statistical power where it will
|
|
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+ do the most good.
|
|
For example, if a particular probe's M-values are always at the extreme
|
|
For example, if a particular probe's M-values are always at the extreme
|
|
of the M-value range (e.g.
|
|
of the M-value range (e.g.
|
|
less than -4) for ADNR samples, but the M-values for that probe in TX and
|
|
less than -4) for ADNR samples, but the M-values for that probe in TX and
|
|
@@ -8903,7 +9025,12 @@ noprefix "false"
|
|
other conditions and estimate an intermediate variance for this probe.
|
|
other conditions and estimate an intermediate variance for this probe.
|
|
In practice, analysis B shows that this approach is adequate, but the voom
|
|
In practice, analysis B shows that this approach is adequate, but the voom
|
|
approach in analysis C is at least as good on all model fit criteria and
|
|
approach in analysis C is at least as good on all model fit criteria and
|
|
- yields a larger estimate for the number of differentially methylated genes.
|
|
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+ yields a larger estimate for the number of differentially methylated genes,
|
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+
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+\emph on
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+and
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+\emph default
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+ it matches up better with the theoretical
|
|
\end_layout
|
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\end_layout
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\begin_layout Standard
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\begin_layout Standard
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@@ -9499,7 +9626,7 @@ status collapsed
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@@ -9564,7 +9691,14 @@ Fraction of genic reads in each sample aligned to non-globin genes, with
|
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|
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|
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@@ -10194,7 +10328,7 @@ All values are given as mean ± standard deviation.
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+\begin_layout Plain Layout
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@@ -10276,7 +10415,7 @@ status collapsed
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