--- title: "RaggedExperiment" author: - name: Martin Morgan affiliation: Roswell Park Comprehensive Cancer Center, Buffalo, NY - name: Marcel Ramos affiliation: Roswell Park Comprehensive Cancer Center, Buffalo, NY date: "`r BiocStyle::doc_date()`" vignette: | %\VignetteIndexEntry{RaggedExperiment} %\VignetteEngine{knitr::rmarkdown} %\VignetteEncoding{UTF-8} output: BiocStyle::html_document: toc_float: true Package: RaggedExperiment bibliography: ../inst/REFERENCES.bib --- # Introduction The `r BiocStyle::Biocpkg("RaggedExperiment")` package provides a flexible data representation for copy number, mutation and other ragged array schema for genomic location data. It aims to provide a framework for a set of samples that have differing numbers of genomic ranges. The `RaggedExperiment` class derives from a `GRangesList` representation and provides a semblance of a rectangular dataset. The row and column dimensions of the `RaggedExperiment` correspond to the number of ranges in the entire dataset and the number of samples represented in the data, respectively. # Installation ```{r, eval = FALSE} if (!require("BiocManager")) install.packages("BiocManager") BiocManager::install("RaggedExperiment") ``` Loading the package: ```{r,include=TRUE,results="hide",message=FALSE,warning=FALSE} library(RaggedExperiment) library(GenomicRanges) ``` # Citing RaggedExperiment Your citations are crucial in keeping our software free and open source. To cite our package see the citation (@Ramos2023-og) in the Reference section. You may also browse to the publication at the link [here][1]. [1]: https://doi.org/10.1093/bioinformatics/btad330 # `RaggedExperiment` class overview A schematic showing the class geometry and supported transformations of the `RaggedExperiment` class is show below. There are three main operations for transforming the `RaggedExperiment` representation: 1) `sparseAssay` 2) `compactAssay` 3) `qreduceAssay` ```{r, echo = FALSE, fig.cap = "RaggedExperiment object schematic. Rows and columns represent genomic ranges and samples, respectively. Assay operations can be performed with (from left to right) compactAssay, qreduceAssay, and sparseAssay.", out.width = "\\maxwidth"} knitr::include_graphics("RaggedExperiment.svg") ``` # Constructing a `RaggedExperiment` object We start with a couple of `GRanges` objects, each representing an individual sample: ```{r} sample1 <- GRanges( c(A = "chr1:1-10:-", B = "chr1:8-14:+", C = "chr2:15-18:+"), score = 3:5) sample2 <- GRanges( c(D = "chr1:1-10:-", E = "chr2:11-18:+"), score = 1:2) ``` Include column data `colData` to describe the samples: ```{r} colDat <- DataFrame(id = 1:2) ``` ## Using `GRanges` objects ```{r} ragexp <- RaggedExperiment( sample1 = sample1, sample2 = sample2, colData = colDat ) ragexp ``` ## Using a `GRangesList` instance ```{r} grl <- GRangesList(sample1 = sample1, sample2 = sample2) RaggedExperiment(grl, colData = colDat) ``` ## Using a `list` of `GRanges` ```{r} rangeList <- list(sample1 = sample1, sample2 = sample2) RaggedExperiment(rangeList, colData = colDat) ``` ## Using a `List` of `GRanges` with metadata __Note__: In cases where a `SimpleGenomicRangesList` is provided along with accompanying metadata (accessed by `mcols`), the metadata is used as the `colData` for the `RaggedExperiment`. ```{r} grList <- List(sample1 = sample1, sample2 = sample2) mcols(grList) <- colDat RaggedExperiment(grList) ``` # Accessors ## Range data ```{r} rowRanges(ragexp) ``` ## Dimension names ```{r} dimnames(ragexp) ``` ## `colData` ```{r} colData(ragexp) ``` # Subsetting ## by dimension Subsetting a `RaggedExperiment` is akin to subsetting a `matrix` object. Rows correspond to genomic ranges and columns to samples or specimen. It is possible to subset using `integer`, `character`, and `logical` indices. ## by genomic ranges The `overlapsAny` and `subsetByOverlaps` functionalities are available for use for `RaggedExperiment`. Please see the corresponding documentation in `RaggedExperiment` and `GenomicRanges`. # *Assay functions `RaggedExperiment` package provides several different functions for representing ranged data in a rectangular matrix via the `*Assay` methods. ## sparseAssay The most straightforward matrix representation of a `RaggedExperiment` will return a matrix of dimensions equal to the product of the number of ranges and samples. ```{r} dim(ragexp) Reduce(`*`, dim(ragexp)) sparseAssay(ragexp) length(sparseAssay(ragexp)) ``` ### Support for sparse matrix output We provide sparse matrix representations with the help of the `Matrix` package. To obtain a sparse representation, the user can use the `sparse = TRUE` argument. ```{r} sparseAssay(ragexp, sparse = TRUE) ``` This representation is of class `dgCMatrix` see the `Matrix` documentation for more details. ## compactAssay Samples with identical ranges are placed in the same row. Non-disjoint ranges are **not** collapsed. ```{r} compactAssay(ragexp) ``` Similarly, to `sparseAssay` the `compactAssay` function provides the option to obtain a sparse matrix representation with the `sparse = TRUE` argument. This will return a `dgCMatrix` class from the `Matrix` package. ```{r} compactAssay(ragexp, sparse = TRUE) ``` ## disjoinAssay This function returns a matrix of disjoint ranges across all samples. Elements of the matrix are summarized by applying the `simplifyDisjoin` functional argument to assay values of overlapping ranges. ```{r} disjoinAssay(ragexp, simplifyDisjoin = mean) ``` ## qreduceAssay The `qreduceAssay` function works with a `query` parameter that highlights a window of ranges for the resulting matrix. The returned matrix will have dimensions `length(query)` by `ncol(x)`. Elements contain assay values for the _i_ th query range and the _j_ th sample, summarized according to the `simplifyReduce` functional argument. For demonstration purposes, we can have a look at the original `GRangesList` and the associated scores from which the current `ragexp` object is derived: ```{r} unlist(grl, use.names = FALSE) ``` This data is represented as `rowRanges` and `assays` in `RaggedExperiment`: ```{r} rowRanges(ragexp) assay(ragexp, "score") ``` Here we provide the "query" region of interest: ```{r} (query <- GRanges(c("chr1:1-14:-", "chr2:11-18:+"))) ``` The `simplifyReduce` argument in `qreduceAssay` allows the user to summarize overlapping regions with a custom method for the given "query" region of interest. We provide one for calculating a weighted average score per query range, where the weight is proportional to the overlap widths between overlapping ranges and a query range. _Note_ that there are three arguments to this function. See the documentation for additional details. ```{r} weightedmean <- function(scores, ranges, qranges) { isects <- pintersect(ranges, qranges) sum(scores * width(isects)) / sum(width(isects)) } ``` A call to `qreduceAssay` involves the `RaggedExperiment`, the `GRanges` query and the `simplifyReduce` functional argument. ```{r} qreduceAssay(ragexp, query, simplifyReduce = weightedmean) ``` See the schematic for a visual representation.

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# Coercion The `RaggedExperiment` provides a family of parallel functions for coercing to the `SummarizedExperiment` class. By selecting a particular assay index (`i`), a parallel assay coercion method can be achieved. Here is the list of function names: * `sparseSummarizedExperiment` * `compactSummarizedExperiment` * `disjoinSummarizedExperiment` * `qreduceSummarizedExperiment` See the documentation for details. ## from dgCMatrix to RaggedExperiment In the special case where the rownames of a `sparseMatrix` are coercible to `GRanges`, `RaggedExperiment` provides the facility to convert sparse matrices into `RaggedExperiment`. This can be done using the `as` coercion method. The example below first creates an example sparse `dgCMatrix` class and then shows the `as` method usage to this end. ```{r} library(Matrix) sm <- Matrix::sparseMatrix( i = c(2, 3, 4, 3, 4, 3, 4), j = c(1, 1, 1, 3, 3, 4, 4), x = c(2L, 4L, 2L, 2L, 2L, 4L, 2L), dims = c(4, 4), dimnames = list( c("chr2:1-10", "chr2:2-10", "chr2:3-10", "chr2:4-10"), LETTERS[1:4] ) ) as(sm, "RaggedExperiment") ``` # Session Information ```{r} sessionInfo() ``` # References