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A little work on Ch3 results

Ryan C. Thompson 6 years ago
parent
commit
a38f1720c3
1 changed files with 114 additions and 16 deletions
  1. 114 16
      thesis.lyx

+ 114 - 16
thesis.lyx

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