---
title: "curatedTCGAData"
date: "`r BiocStyle::doc_date()`"
vignette: |
  %\VignetteIndexEntry{curatedTCGAData}
  %\VignetteEngine{knitr::rmarkdown}
  %\VignetteEncoding{UTF-8}
output:
  BiocStyle::html_document:
    toc_float: true
package: curatedTCGAData
bibliography: ../inst/REFERENCES.bib
---

# Installation

```{r, eval=FALSE}
if (!requireNamespace("BiocManager", quietly = TRUE))
    install.packages("BiocManager")

BiocManager::install("curatedTCGAData")
```

Load packages:

```{r,include=TRUE,results="hide",message=FALSE,warning=FALSE}
library(curatedTCGAData)
library(MultiAssayExperiment)
library(TCGAutils)
```

# Citing `curatedTCGAData`

Your citations are important to the project and help us secure funding. Please
refer to the [References](#references) section to see the @Ramos2020-ya and
@Ramos2017-og citations. For the BibTeX entries, run the `citation` function
(after installation):

```{r,eval=FALSE}
citation("curatedTCGAData")
citation("MultiAssayExperiment")
```

`curatedTCGAData` uses `MultiAssayExperiment` to coordinate and represent the
data. Please cite the `MultiAssayExperiment` [Cancer Research][1] publication.
You can see the PDF of our public data publication on
[JCO Clinical Cancer Informatics][2].

[1]: https://cancerres.aacrjournals.org/content/77/21/e39
[2]: https://ascopubs.org/doi/pdf/10.1200/CCI.19.00119

# Data versions

`curatedTCGAData` now has a version `2.0.1` set of data with a number of
improvements and bug fixes. To access the previous data release,
please use version `1.1.38`. This can be added to the
`curatedTCGAData` function as:

```{r}
head(
    curatedTCGAData(
        diseaseCode = "COAD", assays = "*", version = "1.1.38"
    )
)
```

## Version 2.0.1

Here is a list of changes to the data provided in version `2.0.1`

* provides `RNASeq2Gene` assays with RSEM gene expression values
* Genomic information is present in `RaggedExperiment` objects as `GRCh37`
rather than `37`
* Assays coming from the same platform are now merged and provided as one
(e.g., in `OV` and `GBM`)
* `mRNAArray` data now returns `matrix` data instead of `DataFrame`

# Data source

These data were processed by Broad Firehose pipelines and accessed using
`r BiocStyle::Biocpkg("RTCGAToolbox")`. For details on the preprocessing
methods used, see the
[Broad GDAC documentation](https://broadinstitute.atlassian.net/wiki/spaces/GDAC/pages/844334346/Documentation).

# Downloading datasets

To get a neat table of cancer data available in `curatedTCGAData`, see
the `diseaseCodes` dataset from `TCGAutils`. Availability is indicated by the
`Available` column in the dataset.

```{r}
data('diseaseCodes', package = "TCGAutils")
head(diseaseCodes)
```

Alternatively, you can get the full table of data available using wildcards
`'*'` in the `diseaseCode` argument of the main function:

```{r,eval=FALSE}
curatedTCGAData(
    diseaseCode = "*", assays = "*", version = "2.0.1"
)
```

To see what assays are available for a particular TCGA disease code, leave the
`assays` argument as a wildcard (`'*'`):

```{r}
head(
    curatedTCGAData(
        diseaseCode = "COAD", assays = "*", version = "2.0.1"
    )
)
```

# Caveats for working with TCGA data

Not all TCGA samples are cancer, there are a mix of samples in each of the
33 cancer types. Use `sampleTables` on the `MultiAssayExperiment` object
along with `data(sampleTypes, package = "TCGAutils")` to see what samples are
present in the data. There may be tumors that were used to create multiple
contributions leading to technical replicates. These should be resolved using
the appropriate helper functions such as `mergeReplicates`. Primary tumors
should be selected using `TCGAutils::TCGAsampleSelect` and used as input
to the subsetting mechanisms. See the "Samples in Assays" section of this
vignette.

## ACC dataset example

```{r, message=FALSE}
(accmae <- curatedTCGAData(
    "ACC", c("CN*", "Mutation"), version = "2.0.1", dry.run = FALSE
))
```

**Note**. For more on how to use a `MultiAssayExperiment` please see the
`MultiAssayExperiment` vignette.

### Subtype information

Some cancer datasets contain associated subtype information within the
clinical datasets provided. This subtype information is included in the
metadata of `colData` of the `MultiAssayExperiment` object. To obtain these
variable names, use the `getSubtypeMap` function from TCGA utils:

```{r}
head(getSubtypeMap(accmae))
```

### Typical clinical variables

Another helper function provided by TCGAutils allows users to obtain a set
of consistent clinical variable names across several cancer types.
Use the `getClinicalNames` function to obtain a character vector of common
clinical variables such as vital status, years to birth, days to death, etc.

```{r}
head(getClinicalNames("ACC"))

colData(accmae)[, getClinicalNames("ACC")][1:5, 1:5]
```

### Identifying samples in Assays

The `sampleTables` function gives an overview of sample types / codes
present in the data:

```{r}
sampleTables(accmae)
```

You can use the reference dataset (`sampleTypes`) from the `TCGAutils` package
to interpret the TCGA sample codes above. The dataset provides clinically
meaningful descriptions:

```{r}
data(sampleTypes, package = "TCGAutils")
head(sampleTypes)
```

### Separating samples

Often, an analysis is performed comparing two groups of samples to each other.
To facilitate the separation of samples, the `TCGAsplitAssays` function from
`TCGAutils` identifies all sample types in the assays and moves each into its
own assay. By default, all discoverable sample types are separated into a
separate experiment. In this case we requested only solid tumors and blood
derived normal samples as seen in the `sampleTypes` reference dataset:

```{r}
sampleTypes[sampleTypes[["Code"]] %in% c("01", "10"), ]

TCGAsplitAssays(accmae, c("01", "10"))
```

To obtain a logical vector that could be used for subsetting a
`MultiAsssayExperiment`, refer to `TCGAsampleSelect`. To select only primary
tumors, use the function on the colnames of the `MultiAssayExperiment`:

```{r}
tums <- TCGAsampleSelect(colnames(accmae), "01")
```

### TCGAprimaryTumors convenience

If interested in only the primary tumor samples, `TCGAutils` provides a
convenient operation to extract primary tumors from the MultiAssayExperiment
representation. The `TCGAprimaryTumors` function will return only
samples with primary tumor (either solid tissue or blood) samples using
the above operations in the background:

```{r}
(primaryTumors <- TCGAprimaryTumors(accmae))
```

To view the results, run `sampleTables` again on the output:

```{r}
sampleTables(primaryTumors)
```

### Keeping colData in an extracted Assay

When extracting a single assay from the `MultiAssayExperiment` the user
can conveniently choose to keep the `colData` from the `MultiAssayExperiment`
in the extracted assay **given** that the class of the extracted assay
supports `colData` storage and operations. `SummarizedExperiment` and its
derived data representations support this operation. In this example, we
extract the mutation data as represented by a `RaggedExperiment` which was
designed to have `colData` functionality. The default replacement method
is to 'append' the `MultiAssayExperiment` `colData` to the `RaggedExperiment`
assay. The `mode` argument can also completely replace the `colData` when set
to 'replace'.

```{r}
(accmut <- getWithColData(accmae, "ACC_Mutation-20160128", mode = "append"))
head(colData(accmut)[, 1:4])
```

### Example use of RaggedExperiment

The RaggedExperiment representation provides a matrix view of a `GRangesList`
internal representation. Typical use of a RaggedExperiment involves a number of
functions to reshape 'ragged' measurements into a matrix-like format. These
include `sparseAssay`, `compactAssay`, `disjoinAssay`, and `qreduceAssay`.
See the `RaggedExperiment` vignette for details. In this example, we convert
entrez gene identifiers to numeric in order to show how we can create a sparse
matrix representation of any numeric metadata column in the `RaggedExperiment`.

```{r}
ragex <- accmae[["ACC_Mutation-20160128"]]
## convert score to numeric
mcols(ragex)$Entrez_Gene_Id <- as.numeric(mcols(ragex)[["Entrez_Gene_Id"]])
sparseAssay(ragex, i = "Entrez_Gene_Id", sparse=TRUE)[1:6, 1:3]
```

Users who would like to use the internal `GRangesList` representation can
invoke the coercion method:

```{r}
as(ragex, "GRangesList")
```

## Exporting Data

MultiAssayExperiment provides users with an integrative representation of
multi-omic TCGA data at the convenience of the user. For those users who
wish to use alternative environments, we have provided an export function to
extract all the data from a MultiAssayExperiment instance and write them
to a series of files:

```{r}
td <- tempdir()
tempd <- file.path(td, "ACCMAE")
if (!dir.exists(tempd))
    dir.create(tempd)

exportClass(accmae, dir = tempd, fmt = "csv", ext = ".csv")
```

This works for all data classes stored (e.g., `RaggedExperiment`, `HDF5Matrix`,
`SummarizedExperiment`) in the `MultiAssayExperiment` via the `assays` method
which converts classes to `matrix` format (using individual `assay` methods).

# Session Information {.unnumbered}

<details> <summary> Click here to expand </summary>

```{r}
sessionInfo()
```

</details>

# References {.unnumbered}