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@@ -3686,6 +3686,19 @@ RNA-seq
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of unwanted globin transcripts.
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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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+Add a sentence about Ch5 once written
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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_inset CommandInset label
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LatexCommand label
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@@ -3725,10 +3738,10 @@ glsresetall
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\begin_inset Note Note
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-status collapsed
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+status open
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\begin_layout Plain Layout
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-Reintroduce all abbreviations
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+This causes all abbreviations to be reintroduced.
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\end_layout
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\end_inset
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@@ -3740,23 +3753,6 @@ Reintroduce all abbreviations
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Introduction
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\end_layout
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-\begin_layout Section
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-Approach
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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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-
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-\begin_layout Plain Layout
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-Split Introduction out from Approach for each chapter
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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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CD4
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\begin_inset Formula $^{+}$
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@@ -3832,6 +3828,10 @@ deactivating
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involves positive and negative feedback loops between the two.
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\end_layout
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+\begin_layout Section
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+Approach
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+\end_layout
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+
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\begin_layout Standard
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In order to investigate the relationship between gene expression and these
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histone modifications in the context of naïve and memory CD4
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@@ -11582,15 +11582,29 @@ In this study, a convergence between naïve and memory cells was observed
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\begin_inset Formula $^{+}$
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\end_inset
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- samples at day 14 do not resemble the memory samples at day 0, indicating
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+ samples at day 14 do not resemble the memory samples at day 0, indicating
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that in the specific model of activation used for this experiment, the
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cells are not guaranteed to return to their original pre-activation state,
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or perhaps this process takes substantially longer than 14 days.
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- This is a challenge for the convergence hypothesis because the ideal comparison
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+ This difference is expected, as the cell cultures in this experiment were
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+ treated with IL2 from day 5 onward
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+\begin_inset CommandInset citation
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+LatexCommand cite
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+key "LaMere2016"
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+literal "false"
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+
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+\end_inset
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+
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+, so the signalling environments in which the cells are cultured are different
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+ at day 0 and day 14.
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+\end_layout
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+
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+\begin_layout Standard
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+This is a challenge for the convergence hypothesis because the ideal comparison
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to prove that naïve cells are converging to a resting memory state would
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be to compare the final naïve time point to the Day 0 memory samples, but
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- this comparison is only meaningful if memory cells generally return to
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- the same
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+ this comparison is much more conclusive if memory cells generally return
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+ to the same
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\begin_inset Quotes eld
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\end_inset
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@@ -11661,48 +11675,21 @@ MOFA
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can then be used to identify coordinated patterns of regulation shared
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across many epigenetic marks.
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- If possible, some
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-\begin_inset Quotes eld
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-\end_inset
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-
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-negative control
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-\begin_inset Quotes erd
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-\end_inset
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-
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- marks should be included that are known
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-\emph on
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-not
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-\emph default
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- to be involved in T-cell activation or memory formation.
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Of course, CD4
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\begin_inset Formula $^{+}$
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\end_inset
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- T-cells are not the only adaptive immune cells with memory.
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+ T-cells are not the only adaptive immune cells that exhibit memory formation.
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A similar study could be designed for CD8
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\begin_inset Formula $^{+}$
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\end_inset
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- T-cells, B-cells, and even specific subsets of CD4
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+ T-cells, B-cells, and even specific subsets of CD4
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\begin_inset Formula $^{+}$
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\end_inset
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- T-cells, such as Th1, Th2, Treg, and Th17 cells.
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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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-
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-\begin_layout Plain Layout
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-Sarah: I'm not sure such negative controls exist.
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- Even marks that haven't been linked to T cell differentiation are probably
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- just understudied.
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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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+ T-cells, such as Th1, Th2, Treg, and Th17 cells, to determine whether these
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+ also show convergence.
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\end_layout
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\begin_layout Subsection
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@@ -11956,6 +11943,10 @@ Introduction
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Arrays for diagnostics
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\end_layout
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+\begin_layout Standard
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+Arrays are an attractive platform for diagnostics
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+\end_layout
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+
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\begin_layout Subsection
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Proper pre-processing is essential for array data
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\end_layout
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@@ -11965,10 +11956,10 @@ Microarrays, bead arrays, and similar assays produce raw data in the form
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of fluorescence intensity measurements, with each intensity measurement
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proportional to the abundance of some fluorescently labelled target DNA
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or RNA sequence that base pairs to a specific probe sequence.
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- However, these measurements for each probe are also affected my many technical
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- confounding factors, such as the concentration of target material, strength
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- of off-target binding, the sensitivity of the imaging sensor, and visual
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- artifacts in the image.
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+ However, the fluorescence measurements for each probe are also affected
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+ my many technical confounding factors, such as the concentration of target
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+ material, strength of off-target binding, the sensitivity of the imaging
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+ sensor, and visual artifacts in the image.
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Some array designs also use multiple probe sequences for each target.
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Hence, extensive pre-processing of array data is necessary to normalize
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out the effects of these technical factors and summarize the information
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@@ -11985,23 +11976,6 @@ literal "false"
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.
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\end_layout
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-\begin_layout Section
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-Approach
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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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-
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-\begin_layout Plain Layout
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-Some of this probably goes in intro
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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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The choice of pre-processing algorithms used in the analysis of an array
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data set can have a large effect on the results of that analysis.
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@@ -12014,6 +11988,10 @@ The choice of pre-processing algorithms used in the analysis of an array
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normalization methods tailored to the specific goals of the current analysis.
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\end_layout
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+\begin_layout Section
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+Approach
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+\end_layout
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+
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\begin_layout Subsection
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Clinical diagnostic applications for microarrays require single-channel
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normalization
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@@ -12367,7 +12345,7 @@ M-value
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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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+status collapsed
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\begin_layout Plain Layout
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\align center
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@@ -12518,9 +12496,9 @@ RNA-seq
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be modeled as a smooth curve.
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Hence, the method is sufficiently general to model the mean-variance relationsh
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ip in methylation array data.
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- However, the standard implementation of voom assumes that the input is
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- given in raw read counts, and it must be adapted to run on methylation
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-
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+ However, while the method does not require count data as input, the standard
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+ implementation of voom assumes that the input is given in raw read counts,
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+ and it must be adapted to run on methylation
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\begin_inset Flex Glossary Term (pl)
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status open
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@@ -23012,6 +22990,23 @@ If there are any chapter-independent future directions, put them here.
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Closing remarks
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\end_layout
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+\begin_layout Standard
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+\align center
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+\begin_inset ERT
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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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+addcontentsline{toc}{chapter}{Test}
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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 ERT
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status collapsed
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