%\VignetteIndexEntry{Neve 2006: combined CGH and expression data}
%\VignetteDepends{Biobase,hgu133a.db,annotate}
%\VignetteKeywords{Expression Analysis, CGH}
%\VignettePackage{Neve2006}


%
% NOTE -- ONLY EDIT THE .Rnw FILE!!!  The .tex file is
% likely to be overwritten.
%
\documentclass[12pt]{article}

\usepackage{amsmath,pstricks}
\usepackage[authoryear,round]{natbib}
\usepackage{hyperref}


\textwidth=6.2in
\textheight=8.5in
%\parskip=.3cm
\oddsidemargin=.1in
\evensidemargin=.1in
\headheight=-.3in

\newcommand{\scscst}{\scriptscriptstyle}
\newcommand{\scst}{\scriptstyle}


\newcommand{\Rfunction}[1]{{\texttt{#1}}}
\newcommand{\Robject}[1]{{\texttt{#1}}}
\newcommand{\Rpackage}[1]{{\textit{#1}}}
\newcommand{\Rmethod}[1]{{\texttt{#1}}}
\newcommand{\Rfunarg}[1]{{\texttt{#1}}}
\newcommand{\Rclass}[1]{{\textit{#1}}}

\textwidth=6.2in

\bibliographystyle{plainnat} 
 
\begin{document}
%\setkeys{Gin}{width=0.55\textwidth}


\title{Combining expression and CGH data on breast cancer
cell lines: Neve2006}
\author{VJ Carey, package maintainer, \texttt{<stvjc@channing.harvard.edu>}}
\maketitle

\tableofcontents

\section{Introduction}

The basic source information is obtainable by
interrogating objects in the package.
<<lkm>>=
library(Neve2006)
data(neveRMAmatch)
neveRMAmatch
experimentData(neveRMAmatch)
data(neveCGHmatch)
neveCGHmatch
all.equal(sampleNames(neveRMAmatch), sampleNames(neveCGHmatch))
@

We can see that there are 50 arrays from the U133A platform
and 50 CGH samples, and the sample names match.  The PMID for
the primary manuscript is provided; additional information on
URLs where the base data can be found should be added.

\section{CGH feature data}

Let's look at metadata provided on the first five clones in the
CGH platform:
<<lkc>>=
featureData(neveCGHmatch)[1:5,]
@
The genomic location of clone sequence is tied completely
to the build of the genome used to compute the location.
This information is not provided in the data sources.
We know from the paper that scanning and OncoBAC arrays
were used, but no information about the details of annotation
are immediately available.

Figure 5 of the main paper associates clone RP11-265K5
with a number of genes, including PROSC and BRF2.  Let's
see where this clone lives:
<<lkrp>>=
pData(featureData(neveCGHmatch))[grep("RP11-265K5", 
  featureNames(neveCGHmatch)),]
@
If we use Map Viewer at NCBI for Homo sapiens build 36.2,
we find this clone located at about 37180K, in the vicinity
of genes WHSC1L1, LETM2, FGFR1, PPADPC1B, DDHD2, BAG4, LSM1,
STAR, ASH2L.  Some of these are noted in Figure 5.
The cytoband is 8p12.

\section{Gene expression data in relation to copy number}

Let's identify probe sets annotated to 8p12.
<<doid>>=
library(hgu133a.db)
library(annotate)
cb = as.list(hgu133aMAP)
G8p12ind = grep("8p12", unlist(cb))
ps8p12 = names(unlist(cb)[G8p12ind])
nevex = exprs(neveRMAmatch)[ps8p12,]
syms = as.character(unlist(lookUp(rownames(nevex), "hgu133a", "SYMBOL")))
@

The logratios that measure copy number will be used 'raw'.
<<getlr>>=
nevlr = as.numeric(logRatios(neveCGHmatch)["RP11-265K5",])
@
<<dopl,fig=TRUE>>=
par(mfrow=c(2,2))
for (i in c(2,8,11,20))
 plot( nevlr, nevex[i,], xlab="logratio", ylab="RMA expression",
   main=syms[i])
par(mfrow=c(1,1))
@

Also of interest is the expression distribution for SFRP1.

Connection of these associations to phenotype is straightforward
with proper use of phenoData components of the ExpressionSet
and cghSet objects.  A unified representation of the
two assays that includes
support for linking clone and probe set is in development.

\end{document}


