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@@ -383,11 +383,14 @@ Background & Significance
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Biological motivation
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Biological motivation
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\end_layout
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\end_layout
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-\begin_layout Itemize
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+\begin_layout Subsubsection
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Rejection is the major long-term threat to organ and tissue grafts
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Rejection is the major long-term threat to organ and tissue grafts
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\end_layout
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\end_layout
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-\begin_deeper
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+\begin_layout Standard
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+Organ and tissue transplants are a life-saving
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+\end_layout
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+
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\begin_layout Itemize
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\begin_layout Itemize
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Common mechanisms of rejection
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Common mechanisms of rejection
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\end_layout
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\end_layout
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@@ -405,12 +408,10 @@ Current tests for rejection (tissue biopsy) are invasive and biased
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A blood test based on microarrays would be less biased and invasive
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A blood test based on microarrays would be less biased and invasive
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\end_layout
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\end_layout
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-\end_deeper
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-\begin_layout Itemize
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+\begin_layout Subsubsection
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Memory cells are resistant to immune suppression
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Memory cells are resistant to immune suppression
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\end_layout
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\end_layout
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-\begin_deeper
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\begin_layout Itemize
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\begin_layout Itemize
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Mechanisms of resistance in memory cells are poorly understood
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Mechanisms of resistance in memory cells are poorly understood
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\end_layout
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\end_layout
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@@ -419,13 +420,11 @@ Mechanisms of resistance in memory cells are poorly understood
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A better understanding of immune memory formation is needed
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A better understanding of immune memory formation is needed
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\end_layout
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\end_layout
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-\end_deeper
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-\begin_layout Itemize
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+\begin_layout Subsubsection
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Mesenchymal stem cell infusion is a promising new treatment to prevent/delay
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Mesenchymal stem cell infusion is a promising new treatment to prevent/delay
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rejection
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rejection
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\end_layout
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\end_layout
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-\begin_deeper
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\begin_layout Itemize
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\begin_layout Itemize
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Demonstrated in mice, but not yet in primates
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Demonstrated in mice, but not yet in primates
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\end_layout
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\end_layout
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@@ -434,7 +433,6 @@ Demonstrated in mice, but not yet in primates
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Mechanism currently unknown, but MSC are known to be immune modulatory
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Mechanism currently unknown, but MSC are known to be immune modulatory
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\end_layout
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\end_layout
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-\end_deeper
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\begin_layout Subsection
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\begin_layout Subsection
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Overview of bioinformatic analysis methods
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Overview of bioinformatic analysis methods
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\end_layout
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\end_layout
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@@ -444,11 +442,24 @@ An overview of all the methods used, including what problem they solve,
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what assumptions they make, and a basic description of how they work.
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what assumptions they make, and a basic description of how they work.
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\end_layout
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\end_layout
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-\begin_layout Itemize
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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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+Many of these points are also addressed in the approach sections of the
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+ following chapters? Redundant?
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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 Subsubsection
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ChIP-seq Peak calling
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ChIP-seq Peak calling
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\end_layout
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\end_layout
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-\begin_deeper
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\begin_layout Itemize
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\begin_layout Itemize
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Cross-correlation analysis to determine fragment size
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Cross-correlation analysis to determine fragment size
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\end_layout
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\end_layout
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@@ -458,7 +469,7 @@ Broad vs narrow peaks
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\end_layout
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\end_layout
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\begin_layout Itemize
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\begin_layout Itemize
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-SICER for broad peaks
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+MACS for narrow, SICER for broad peaks
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\end_layout
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\end_layout
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\begin_layout Itemize
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\begin_layout Itemize
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@@ -469,12 +480,10 @@ IDR for biologically reproducible peaks
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csaw peak filtering guidelines for unbiased downstream analysis
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csaw peak filtering guidelines for unbiased downstream analysis
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\end_layout
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\end_layout
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-\end_deeper
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-\begin_layout Itemize
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+\begin_layout Subsubsection
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Normalization is non-trivial and application-dependant
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Normalization is non-trivial and application-dependant
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\end_layout
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\end_layout
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-\begin_deeper
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\begin_layout Itemize
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\begin_layout Itemize
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Expression arrays: RMA & fRMA; why fRMA is needed
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Expression arrays: RMA & fRMA; why fRMA is needed
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\end_layout
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\end_layout
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@@ -493,12 +502,10 @@ ChIP-seq: complex with many considerations, dependent on experimental methods,
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biological system, and analysis goals
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biological system, and analysis goals
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\end_layout
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\end_layout
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-\end_deeper
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-\begin_layout Itemize
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+\begin_layout Subsubsection
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Limma: The standard linear modeling framework for genomics
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Limma: The standard linear modeling framework for genomics
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\end_layout
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\end_layout
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-\begin_deeper
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\begin_layout Itemize
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\begin_layout Itemize
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empirical Bayes variance modeling: limma's core feature
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empirical Bayes variance modeling: limma's core feature
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\end_layout
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\end_layout
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@@ -516,26 +523,19 @@ voom: Extend with precision weights to model mean-variance trend
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arrayWeights and duplicateCorrelation to handle complex variance structures
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arrayWeights and duplicateCorrelation to handle complex variance structures
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\end_layout
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\end_layout
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-\end_deeper
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-\begin_layout Itemize
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+\begin_layout Subsubsection
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sva and ComBat for batch correction
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sva and ComBat for batch correction
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\end_layout
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\end_layout
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-\begin_layout Itemize
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+\begin_layout Subsubsection
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Factor analysis: PCA, MDS, MOFA
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Factor analysis: PCA, MDS, MOFA
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\end_layout
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\end_layout
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-\begin_deeper
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\begin_layout Itemize
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\begin_layout Itemize
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Batch-corrected PCA is informative, but careful application is required
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Batch-corrected PCA is informative, but careful application is required
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to avoid bias
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to avoid bias
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\end_layout
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\end_layout
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-\end_deeper
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-\begin_layout Itemize
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-Gene set analysis: camera and SPIA
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-\end_layout
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-
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\begin_layout Section
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\begin_layout Section
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Innovation
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Innovation
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\end_layout
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\end_layout
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@@ -11754,11 +11754,10 @@ Currently, the source of these unwanted systematic variations in the data
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to maximize the chance that the training algorithm will be able to identify
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to maximize the chance that the training algorithm will be able to identify
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highly predictive probes from those remaining.
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highly predictive probes from those remaining.
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Lastly, it is possible that some of this unwanted variation is a result
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Lastly, it is possible that some of this unwanted variation is a result
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- of the assay being used.
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- Assaying DNA methylation using bisulphite sequencing may sidestep the issue
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- in this case, although this carries the risk that the sequencing assay
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- will have its own set of biases that must be corrected for in a different
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- way.
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+ of the array-based assay being used and would be eliminated by switching
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+ to assaying DNA methylation using bisulphite sequencing.
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+ However, this carries the risk that the sequencing assay will have its
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+ own set of biases that must be corrected for in a different way.
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\end_layout
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\end_layout
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\begin_layout Chapter
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\begin_layout Chapter
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