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@@ -682,7 +682,6 @@ literal "false"
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\end_inset
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.
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-
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\end_layout
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\begin_layout Itemize
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@@ -3065,21 +3064,6 @@ Averages and log ratios were computed for every probe in each of 20 blood
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Adapting voom to methylation array data improves model fit
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\end_layout
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-\begin_layout Itemize
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-voom, precision weights, and sva improved model fit
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-\end_layout
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-
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-\begin_deeper
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-\begin_layout Itemize
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-Also increased sensitivity for detecting differential methylation
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-\end_layout
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-
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-\end_deeper
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-\begin_layout Itemize
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-Figure showing (a) heteroskedasticy without voom, (b) voom-modeled mean-variance
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- trend, and (c) homoskedastic mean-variance trend after running voom
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-\end_layout
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-
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\begin_layout Standard
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\begin_inset Flex TODO Note (inline)
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status open
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@@ -3263,6 +3247,29 @@ Residual mean-variance trend after modeling with SVA, sample weights, and
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\end_layout
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+\begin_layout Itemize
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+U-shaped mean-var trend visible in data, even after accounting for unobserved
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+ confounders (SVA) and array quality (sample weights)
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+\end_layout
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+
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+\begin_layout Itemize
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+\begin_inset Quotes eld
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+\end_inset
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+
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+vooma
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+\begin_inset Quotes erd
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+\end_inset
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+
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+ models this trend, and after voom, the mean-variance trend is flat and
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+ the median varaiance is approximately 1 (0 on log scale)
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+\end_layout
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+
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+\begin_layout Itemize
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+M-value distribution is bimodal - expected if most CpG methylation states
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+ are homogeneous among cell populations, either all methylated or all unmethylat
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+ed.
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+\end_layout
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+
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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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@@ -3410,6 +3417,72 @@ Association of sample weights with clinical covariates.
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\end_layout
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+\begin_layout Standard
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+\begin_inset Flex TODO Note (inline)
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+status open
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+
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+\begin_layout Plain Layout
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+Redo the sample weight boxplot with notches and without fill colors
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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 Standard
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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 open
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+
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+\begin_layout Plain Layout
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+\begin_inset Graphics
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+ filename graphics/methylvoom/unadj.dupcor.sva.voomaw/sample-weights-PAGE3.pdf
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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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+\begin_layout Plain Layout
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+\begin_inset CommandInset label
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+LatexCommand label
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+name "fig:diabetes-sample-weights"
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+
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+\end_inset
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+
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+
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+\series bold
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+Boxplot of sample quality weights grouped by diabetes diagnosis.
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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 Plain Layout
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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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+\end_layout
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+
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+\begin_layout Itemize
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+Based on estimated sample weights, T2D samples are significantly more variable
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+ than T1D samples (t-test p = 1.06e-3)
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+\end_layout
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+
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+\begin_layout Itemize
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+Should not affect further analysis
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+\end_layout
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+
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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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@@ -3908,6 +3981,31 @@ Re-generate p-value histograms for all relevant contrasts in a single figure.
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\end_layout
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+\begin_layout Itemize
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+Better variance properties in analyses B and C give more significant probes
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+ (10% FDR)
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+\begin_inset CommandInset ref
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+LatexCommand ref
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+reference "tab:methyl-num-signif"
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+plural "false"
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+caps "false"
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+noprefix "false"
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+
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+\end_inset
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+
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+, more probes estimated to be differentially methylated
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+\begin_inset CommandInset ref
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+LatexCommand ref
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+reference "tab:methyl-est-nonnull"
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+plural "false"
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+caps "false"
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+noprefix "false"
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+
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+\end_inset
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+
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+, and better looking p-value distributions [histogram figures].
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+\end_layout
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+
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\begin_layout Section
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Discussion
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\end_layout
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