---
title: 'Use case: leukemia signatures (Den Boer, 2009)'
author: "Jacques van Helden"
date: '`r Sys.Date()`'
output:
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    fig_width: 7
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    slide_level: 2
    theme: Montpellier
    toc: yes
  ioslides_presentation:
    colortheme: dolphin
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font-import: http://fonts.googleapis.com/css?family=Risque
subtitle: Analyse Statistique des données Génomiques (ASG)
font-family: Garamond
transition: linear
---

```{r include=FALSE, echo=FALSE, eval=TRUE}
library(knitr)
options(width=300)
knitr::opts_chunk$set(
  fig.width = 7, fig.height = 5, 
  fig.path='figures',
  fig.align = "center", 
  size = "tiny", 
  echo = FALSE, eval=TRUE, 
  warning = FALSE, message = FALSE, 
  results = TRUE, comment = "")
# knitr::asis_output("\\footnotesize")

```

## Study case

We present here a dataset that will be used as study case to apply different approaches of multivariate analysis:

- data exploration
- multidimensional scaling
- differential analysis
- clustering (unsupervised classification)
- supervised classification

**Reference:** Den Boer ML *et al.* (2009). A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol. 2009 10:125-34. [[doi: 10.1016/S1470-2045(08)70339-5](http://doi.org/10.1016/S1470-2045(08)70339-5)], 
[[PMID 19138562](https://www.ncbi.nlm.nih.gov/pubmed/19138562)]. Data available at Gene Expression Omnibus, series [[GSE13425](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13425)]


## Identification of signatures for subtypes of leukemia

```{r denboer_procedure, out.height="40%", out.width="40%", fig.cap="Figure 1 from Den Boer et al. (2009). "}
include_graphics("images/Den_Boer_2009_Fig1_signature_identification.png") 
```

## Hierarchical clustering of genes and samples

```{r denboer_hclust, out.height="70%", out.width="70%", fig.cap="Figure 2 from Den Boer et al. (2009). "}
include_graphics("images/Den_Boer_2009_Fig2_hierarchical_clustering.png") 
```

## Survival curves


```{r denboer_survival, out.height="80%", out.width="80%", fig.cap="Figure 3 from Den Boer et al. (2009). "}
include_graphics("images/Den_Boer_2009_Fig3_survival.png") 
```