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@@ -79,6 +79,24 @@ InsetLayout "Flex:Glossary Term (Capital)"
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CustomPars false
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End
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+InsetLayout "Flex:Glossary Term (pl)"
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+ LyxType custom
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+ LabelString glspl
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+ LatexType command
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+ LatexName glspl*
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+ InToc true
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+ CustomPars false
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+End
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+
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+InsetLayout "Flex:Glossary Term (Capital, pl)"
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+ LyxType custom
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+ LabelString Glspl
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+ LatexType command
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+ LatexName Glspl*
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+ InToc true
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+ CustomPars false
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+End
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+
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InsetLayout "Flex:Glossary Term (glstext)"
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LyxType custom
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LabelString glstext
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@@ -180,9 +198,10 @@ End
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\use_package stmaryrd 1
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\use_package undertilde 1
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\cite_engine biblatex
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-\cite_engine_type authoryear
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+\cite_engine_type numerical
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\biblio_style plain
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-\biblatex_bibstyle authoryear
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+\biblio_options sorting=none
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+\biblatex_bibstyle numeric
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\biblatex_citestyle numeric
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\use_bibtopic false
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\use_indices false
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@@ -269,6 +288,27 @@ in partial fulfillment of the requirements for the degree of
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October 2019
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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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+To remove TODOs and watermark: Add
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+\begin_inset Quotes eld
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+\end_inset
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+
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+final
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+\begin_inset Quotes erd
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+\end_inset
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+
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+ to the document class custom options.
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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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[Copyright notice]
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\end_layout
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@@ -583,7 +623,7 @@ Structure of the thesis
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status open
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\begin_layout Plain Layout
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-This section might even go before the Chapter 1 header
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+Put at end up intro
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\end_layout
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\end_inset
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@@ -698,7 +738,7 @@ literal "false"
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of immune memory.
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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Diagnosis and treatment of allograft rejection is a major challenge
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\end_layout
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@@ -799,7 +839,7 @@ for cause
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biopsies
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\begin_inset CommandInset citation
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LatexCommand cite
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-key "Wilkinson2006,Salomon2002,Patel2018,Zachariah2018"
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+key "Salomon2002,Wilkinson2006,Patel2018,Zachariah2018"
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literal "false"
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\end_inset
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@@ -864,7 +904,7 @@ literal "false"
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on the scale of days to weeks, rather than months.
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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Memory cells are resistant to immune suppression
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\end_layout
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@@ -960,22 +1000,32 @@ literal "false"
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and regulation is required.
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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MSC infusion to improve transplant outcomes (prevent/delay rejection)
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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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+One promising experimental treatment for transplant rejection involves the
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+ infusion of
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+\begin_inset Flex Glossary Term (pl)
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status open
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\begin_layout Plain Layout
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-Do I still talk about this? It's the motivation for chapter 4, but I don't
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- actually present any work related to MSCs.
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+MSC
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\end_layout
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\end_inset
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+\begin_inset CommandInset nomenclature
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+LatexCommand nomenclature
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+symbol "MSC"
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+description "mesenchymal stem cell"
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+literal "true"
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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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\begin_layout Itemize
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@@ -1013,10 +1063,23 @@ RNA-seq
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at serial time points
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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Investigate dynamics of histone marks in CD4 T-cell activation and memory
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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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+Put this at end of intro as part of a description to structure of thesis
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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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Previous studies have looked at single snapshots of histone marks
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\end_layout
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@@ -1025,10 +1088,23 @@ Previous studies have looked at single snapshots of histone marks
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Instead, look at changes in histone marks across activation and memory
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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High-throughput sequencing and microarray technologies
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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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+This will serve as transition to bioinf
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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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Powerful methods for assaying gene expression and epigenetics across entire
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genomes
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@@ -1052,19 +1128,6 @@ Overview of bioinformatic analysis methods
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\begin_inset Flex TODO Note (inline)
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status open
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-\begin_layout Plain Layout
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-Some kind of transition into bioinformatics would be good here
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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 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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Also cite somewhere: R, Bioconductor
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\end_layout
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@@ -4059,14 +4122,11 @@ TSS
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.
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For genes with multiple annotated
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-\begin_inset ERT
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+\begin_inset Flex Glossary Term (pl)
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status open
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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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-glspl*{TSS}
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+TSS
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\end_layout
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\end_inset
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@@ -4082,14 +4142,11 @@ TSS
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\end_inset
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individually, and any promoters that overlapped (due to multiple
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-\begin_inset ERT
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+\begin_inset Flex Glossary Term (pl)
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status open
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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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-glspl*{TSS}
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+TSS
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\end_layout
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\end_inset
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@@ -4813,14 +4870,11 @@ noprefix "false"
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.
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-\begin_inset ERT
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+\begin_inset Flex Glossary Term (Capital, pl)
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status open
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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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-Glspl*{LF}
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+LF
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\end_layout
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\end_inset
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@@ -6982,6 +7036,131 @@ end{landscape}
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\end_layout
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+\begin_layout Standard
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+We hypothesized that if naïve cells had differentiated into memory cells
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+ by Day 14, then their patterns of expression and histone modification should
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+ converge with those of memory cells at Day 14.
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+ Figure
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+\begin_inset CommandInset ref
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+LatexCommand ref
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+reference "fig:PCoA-promoters"
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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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+ shows the patterns of variation in all 3 histone marks in the promoter
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+ regions of the genome using
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+\begin_inset Flex Glossary Term
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+status open
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+
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+\begin_layout Plain Layout
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+PCoA
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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 CommandInset nomenclature
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+LatexCommand nomenclature
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+symbol "PCoA"
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+description "principal coordinate analysis"
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+literal "false"
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+
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+\end_inset
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+
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+.
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+ All 3 marks show a noticeable convergence between the naïve and memory
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+ samples at day 14, visible as an overlapping of the day 14 groups on each
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+ plot.
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+ This is consistent with the counts of significantly differentially modified
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+ promoters and estimates of the total numbers of differentially modified
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+ promoters shown in Table
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+\begin_inset CommandInset ref
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+LatexCommand ref
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+reference "tab:Number-signif-promoters"
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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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+.
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+ For all histone marks, evidence of differential modification between naïve
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+ and memory samples was detected at every time point except day 14.
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+ The day 14 convergence pattern is also present in the
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+\begin_inset Flex Glossary Term
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+status open
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+
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+\begin_layout Plain Layout
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+RNA-seq
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+\end_layout
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+
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+\end_inset
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+
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+ data (Figure
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+\begin_inset CommandInset ref
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+LatexCommand ref
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+reference "fig:RNA-PCA-group"
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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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+), albeit in the 2nd and 3rd principal coordinates, indicating that it is
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+ not the most dominant pattern driving gene expression.
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+ Taken together, the data show that promoter histone methylation for these
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+ 3 histone marks and RNA expression for naïve and memory cells are most
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+ similar at day 14, the furthest time point after activation.
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+
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+\begin_inset Flex Glossary Term
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+status open
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+
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+\begin_layout Plain Layout
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+MOFA
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+\end_layout
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+
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+\end_inset
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+
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+ was also able to capture this day 14 convergence pattern in
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+\begin_inset Flex Glossary Term
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+status open
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+
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+\begin_layout Plain Layout
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+LF
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+\end_layout
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+
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+\end_inset
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+
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+5 (Figure
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+\begin_inset CommandInset ref
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+LatexCommand ref
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+reference "fig:mofa-lf-scatter"
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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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+), which accounts for shared variation across all 3 histone marks and the
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+
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+\begin_inset Flex Glossary Term
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+status open
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+
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+\begin_layout Plain Layout
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+RNA-seq
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+\end_layout
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+
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+\end_inset
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+
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+ data, confirming that this convergence is a coordinated pattern across
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+ all 4 data sets.
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+ While this observation does not prove that the naïve cells have differentiated
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+ into memory cells at Day 14, it is consistent with that hypothesis.
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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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placement p
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@@ -6994,7 +7173,7 @@ status open
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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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@@ -7039,7 +7218,7 @@ PCoA plot of H3K4me2 promoters, after subtracting surrogate variables
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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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@@ -7129,7 +7308,7 @@ PCoA plot of H3K27me3 promoters, after subtracting surrogate variables
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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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@@ -7194,131 +7373,6 @@ PCoA plots for promoter ChIP-seq and expression RNA-seq data
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\end_layout
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-\begin_layout Standard
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-We hypothesized that if naïve cells had differentiated into memory cells
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- by Day 14, then their patterns of expression and histone modification should
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- converge with those of memory cells at Day 14.
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- Figure
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-\begin_inset CommandInset ref
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-LatexCommand ref
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-reference "fig:PCoA-promoters"
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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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- shows the patterns of variation in all 3 histone marks in the promoter
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- regions of the genome using
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-\begin_inset Flex Glossary Term
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-status open
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-
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-\begin_layout Plain Layout
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-PCoA
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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 CommandInset nomenclature
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-LatexCommand nomenclature
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-symbol "PCoA"
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-description "principal coordinate analysis"
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-literal "false"
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-
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-\end_inset
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-
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-.
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- All 3 marks show a noticeable convergence between the naïve and memory
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- samples at day 14, visible as an overlapping of the day 14 groups on each
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- plot.
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- This is consistent with the counts of significantly differentially modified
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- promoters and estimates of the total numbers of differentially modified
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- promoters shown in Table
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-\begin_inset CommandInset ref
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-LatexCommand ref
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-reference "tab:Number-signif-promoters"
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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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-.
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- For all histone marks, evidence of differential modification between naïve
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- and memory samples was detected at every time point except day 14.
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- The day 14 convergence pattern is also present in the
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-\begin_inset Flex Glossary Term
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-status open
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-
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-\begin_layout Plain Layout
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-RNA-seq
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-\end_layout
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-
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-\end_inset
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-
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- data (Figure
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-\begin_inset CommandInset ref
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-LatexCommand ref
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-reference "fig:RNA-PCA-group"
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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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-), albeit in the 2nd and 3rd principal coordinates, indicating that it is
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- not the most dominant pattern driving gene expression.
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- Taken together, the data show that promoter histone methylation for these
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- 3 histone marks and RNA expression for naïve and memory cells are most
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- similar at day 14, the furthest time point after activation.
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-
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-
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-
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- was also able to capture this day 14 convergence pattern in
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-
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-
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-5 (Figure
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-\begin_inset CommandInset ref
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-LatexCommand ref
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-reference "fig:mofa-lf-scatter"
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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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-
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-), which accounts for shared variation across all 3 histone marks and the
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-status open
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-RNA-seq
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-\end_layout
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-
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- data, confirming that this convergence is a coordinated pattern across
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- all 4 data sets.
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- While this observation does not prove that the naïve cells have differentiated
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- into memory cells at Day 14, it is consistent with that hypothesis.
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-\end_layout
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-
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\begin_layout Subsection
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Effect of H3K4me2 and H3K4me3 promoter coverage upstream vs downstream of
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TSS
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@@ -8637,14 +8691,11 @@ TSS
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(Cluster 6).
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Referring to these opposing pairs of clusters as axes of variation is justified
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, because they correspond precisely to the first 3
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-\begin_inset ERT
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-status collapsed
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+\begin_inset Flex Glossary Term (pl)
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+status open
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\begin_layout Plain Layout
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-
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-\backslash
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-glspl*{PC}
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+PC
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\end_layout
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\end_inset
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@@ -9071,14 +9122,11 @@ LF
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5.
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Like all the
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-\begin_inset ERT
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+\begin_inset Flex Glossary Term (pl)
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status open
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\begin_layout Plain Layout
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-
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-\backslash
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-glspl*{LF}
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+LF
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\end_layout
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\end_inset
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@@ -16802,14 +16850,11 @@ RNA-seq
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\end_inset
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in primate blood samples that uses complimentary
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-\begin_inset ERT
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+\begin_inset Flex Glossary Term (pl)
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status open
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\begin_layout Plain Layout
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-
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-\backslash
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-glspl*{oligo}
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+oligo
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\end_layout
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\end_inset
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@@ -17035,14 +17080,11 @@ literal "false"
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.
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In the present report, we evaluated globin reduction using custom blocking
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-\begin_inset ERT
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+\begin_inset Flex Glossary Term (pl)
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status open
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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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-glspl*{oligo}
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+oligo
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\end_layout
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\end_inset
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@@ -17136,14 +17178,11 @@ Globin Blocking
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\begin_layout Standard
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Four
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-\begin_inset ERT
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+\begin_inset Flex Glossary Term (pl)
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status open
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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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-glspl*{oligo}
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+oligo
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\end_layout
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\end_inset
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@@ -17156,14 +17195,11 @@ glspl*{oligo}
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two hybridization sites for HBB and 2 sites for HBA (the chosen sites were
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identical in both HBA genes).
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All
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-\begin_inset ERT
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+\begin_inset Flex Glossary Term (pl)
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status open
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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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-glspl*{oligo}
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+oligo
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\end_layout
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\end_inset
|
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@@ -17263,14 +17299,11 @@ mRNA
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PolyA selected RNA was then combined with 8 pmol of HBA1/2 (site 1), 8
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pmol of HBA1/2 (site 2), 12 pmol of HBB (site 1) and 12 pmol of HBB (site
|
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2)
|
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-\begin_inset ERT
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+\begin_inset Flex Glossary Term (pl)
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status open
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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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-glspl*{oligo}
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+oligo
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\end_layout
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\end_inset
|
|
@@ -17288,14 +17321,11 @@ glspl*{oligo}
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sher).
|
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A second “unblocked” library was prepared in the same way for each sample
|
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|
but replacing the blocking
|
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|
-\begin_inset ERT
|
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+\begin_inset Flex Glossary Term (pl)
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status open
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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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-glspl*{oligo}
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+oligo
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\end_layout
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\end_inset
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@@ -18524,14 +18554,11 @@ GB
|
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\end_inset
|
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-\begin_inset ERT
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+\begin_inset Flex Glossary Term (pl)
|
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status open
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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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-glspl*{oligo}
|
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+oligo
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\end_layout
|
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\end_inset
|
|
@@ -19322,28 +19349,22 @@ noprefix "false"
|
|
|
).
|
|
|
Other than the 3 designated alpha and beta globin genes, two other genes
|
|
|
stand out as having especially large negative
|
|
|
-\begin_inset ERT
|
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|
+\begin_inset Flex Glossary Term (pl)
|
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status open
|
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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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|
-glspl*{logFC}
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+logFC
|
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|
\end_layout
|
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|
\end_inset
|
|
|
|
|
|
: HBD and LOC1021365.
|
|
|
HBD, delta globin, is most likely targeted by the blocking
|
|
|
-\begin_inset ERT
|
|
|
+\begin_inset Flex Glossary Term (pl)
|
|
|
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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-glspl*{oligo}
|
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+oligo
|
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\end_layout
|
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\end_inset
|
|
@@ -19395,14 +19416,11 @@ GB
|
|
|
\end_inset
|
|
|
|
|
|
|
|
|
-\begin_inset ERT
|
|
|
+\begin_inset Flex Glossary Term (pl)
|
|
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status open
|
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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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|
-glspl*{oligo}
|
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|
+oligo
|
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|
\end_layout
|
|
|
|
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|
\end_inset
|
|
@@ -20269,14 +20287,11 @@ GB
|
|
|
samples.
|
|
|
However, given that both datasets are derived from the same biological
|
|
|
samples and have nearly equal
|
|
|
-\begin_inset ERT
|
|
|
-status collapsed
|
|
|
+\begin_inset Flex Glossary Term (pl)
|
|
|
+status open
|
|
|
|
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|
\begin_layout Plain Layout
|
|
|
-
|
|
|
-
|
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|
-\backslash
|
|
|
-glspl*{BCV}
|
|
|
+BCV
|
|
|
\end_layout
|
|
|
|
|
|
\end_inset
|
|
@@ -20473,14 +20488,11 @@ GB
|
|
|
\end_inset
|
|
|
|
|
|
|
|
|
-\begin_inset ERT
|
|
|
+\begin_inset Flex Glossary Term (pl)
|
|
|
status open
|
|
|
|
|
|
\begin_layout Plain Layout
|
|
|
-
|
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|
-
|
|
|
-\backslash
|
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|
-glspl*{oligo}
|
|
|
+oligo
|
|
|
\end_layout
|
|
|
|
|
|
\end_inset
|
|
@@ -20546,14 +20558,11 @@ RNA-seq
|
|
|
the relative levels of non-globin genes.
|
|
|
Based on these results, globin transcript reduction using sequence-specific,
|
|
|
complementary blocking
|
|
|
-\begin_inset ERT
|
|
|
+\begin_inset Flex Glossary Term (pl)
|
|
|
status open
|
|
|
|
|
|
\begin_layout Plain Layout
|
|
|
-
|
|
|
-
|
|
|
-\backslash
|
|
|
-glspl*{oligo}
|
|
|
+oligo
|
|
|
\end_layout
|
|
|
|
|
|
\end_inset
|
|
@@ -20648,6 +20657,7 @@ Closing remarks
|
|
|
\end_layout
|
|
|
|
|
|
\begin_layout Standard
|
|
|
+\align center
|
|
|
\begin_inset ERT
|
|
|
status collapsed
|
|
|
|
|
@@ -20675,20 +20685,7 @@ bibname}{References}
|
|
|
LatexCommand bibtex
|
|
|
btprint "btPrintCited"
|
|
|
bibfiles "code-refs,refs-PROCESSED"
|
|
|
-options "bibtotoc,unsrt"
|
|
|
-
|
|
|
-\end_inset
|
|
|
-
|
|
|
-
|
|
|
-\end_layout
|
|
|
-
|
|
|
-\begin_layout Standard
|
|
|
-\begin_inset Flex TODO Note (inline)
|
|
|
-status open
|
|
|
-
|
|
|
-\begin_layout Plain Layout
|
|
|
-Check bib entry formatting & sort order
|
|
|
-\end_layout
|
|
|
+options "bibtotoc"
|
|
|
|
|
|
\end_inset
|
|
|
|
|
@@ -20700,8 +20697,9 @@ Check bib entry formatting & sort order
|
|
|
status open
|
|
|
|
|
|
\begin_layout Plain Layout
|
|
|
-Check in-text citation format.
|
|
|
- Probably don't just want [1], [2], etc.
|
|
|
+Reference URLs that span pages have clickable links that include the page
|
|
|
+ numbers and watermark.
|
|
|
+ Try to fix that.
|
|
|
\end_layout
|
|
|
|
|
|
\end_inset
|