R/CellCounts.R

In COMPASS: Combinatorial Polyfunctionality Analysis of Single Cells

globalVariables(c("name","trtLabels","show_colnames","runApp"))


##' Compute Number of Cells Positive for Certain Cytokine Combinations
##'
##' Compute the number of cells expressing a particular
##' combination of markers for each sample.
##'
##' @param data Either a \code{COMPASSContainer}, or a list of matrices.
##'   Each matrix \code{i} is of dimension \code{N_i} cells (rows) by
##'   \code{K} common markers (columns).
##' @param combinations A list of 'combinations', used to denote the
##'   subsets of interest. See the examples for usage.
##' @export
##' @seealso \code{\link{Combinations}}
##' @examples
##' set.seed(123)
##' ## generate 10 simulated matrices of flow data
##' K <- 6 ## number of markers
##' data <- replicate(10, simplify=FALSE, {
##'   m <- matrix( rnorm(1E4 * K, 2000, 1000 ), ncol=K )
##'   m[m < 2500] <- 0
##'   colnames(m) <- c("IL2", "IL4", "IL6", "Mip1B", "IFNg", "TNFa")
##'   return(m)
##' })
##' names(data) <- sample(letters, 10)
##' head( data[[1]] )
##'
##' ## generate counts over all available combinations of markers in data
##' str(CellCounts(data)) ## 64 columns, as all 2^6 combinations expressed
##'
##' ## generate marginal counts
##' combos <- list(1, 2, 3, 4, 5, 6) ## marginal cell counts
##' cc <- CellCounts(data, combos)
##'
##' ## a base R way of doing the same thing
##' f <- function(data) {
##'   do.call(rbind, lapply(data, function(x) apply(x, 2, function(x) sum(x > 0))))
##' }
##' cc2 <- f(data)
##'
##' ## check that they're identical
##' stopifnot(identical( unname(cc), unname(cc2) ))
##'
##' ## We can also generate cell counts by expressing various combinations
##' ## of markers (names) in the data.
##'
##' ## count cells expressing IL2 or IL4
##' CellCounts(data, "IL2|IL4")
##'
##' ## count cells expressing IL2, IL4 or IL6
##' CellCounts(data, "IL2|IL4|IL6")
##'
##' ## counts for each of IL2, IL4, IL6 (marginally)
##' CellCounts(data, c("IL2", "IL4", "IL6"))
##'
##' ## counts for cells that are IL2 positive and IL4 negative
##' CellCounts(data, "IL2 & !IL4")
##'
##' ## expressing the same intent with indices
##' CellCounts(data, list(c(1, -2)))
##'
##' ## all possible combinations
##' str(CellCounts(data, Combinations(6)))
##'
##' ## can also call on COMPASSContainers
##' data(COMPASS)
##' CellCounts(CC, "M1&M2")
CellCounts <- function(data, combinations) {
  UseMethod("CellCounts")
}

##' @export
CellCounts.COMPASSContainer <- function(data, combinations) {
  data <- data$data
  NextMethod("CellCounts")
}

.CellCounts_character <- function(data, combinations) {

  ## Pre-parse the combinations by expanding entries of the form
  ## "A*B*C" to
  ##
  ## A & B & C
  ## A & B & !C
  ## A & !B & C
  ## ...
  ##
  ## TODO: Handle things like A&(B*C)
  combos <- lapply(combinations, function(x) {

    ## Bail if no '*'
    if (!grepl("*", x, fixed=TRUE)) return(x)

    ## Bail if unsupported combination seen
    if (grepl("*", x, fixed=TRUE) && grepl("[&|]", x, perl=TRUE)) {
      stop("currently cannot combine '*' expander with '&' or '|'",
        call.=FALSE)
    }

    ## Generate a matrix of 0s and 1s that forms the same 'structure'
    splat <- unlist(strsplit(x, "*", fixed = TRUE))
    n <- length(splat)
    values <- do.call(
      function(...) {
        expand.grid(..., KEEP.OUT.ATTRS = FALSE)
      },
      replicate(n, c(0, 1), simplify = FALSE)
    )

    ## Replace the 0s and 1s with appropriate names
    for (i in seq_along(values)) {
      values[, i] <- swap(values[, i],
        c(0, 1),
        c(splat[i], paste0("!", splat[i]))
      )
    }

    ## Paste and return the output
    do.call(
      function(...) paste(..., sep = "&"),
      values,

    )

  })

  combos <- unlist(combos)

  output <- .Call(C_COMPASS_CellCounts_character,
    data,
    lapply(combos, function(x) parse(text=x))
  )
  rownames(output) <- names(data)
  colnames(output) <- combos
  return(output)
}

.CellCounts_numeric <- function(data, combinations) {

  cn <- colnames(data[[1]])
  if (any(is.null(cn)) || any(is.na(cn))) {
    warning("The column names of the matrices in your data are NA or NULL;",
      " they need to be set for the output to have sensible names.")
  }

  combinations <- lapply(combinations, function(combo) {
    if (is.character(combo)) {
      splat <- unlist( strsplit(combo, "&", fixed=TRUE) )
      return( sapply(splat, function(y) {
        if (substring(y, 1, 1) == "!") {
          return( match( substring(y, 2, nchar(y)), cn ) )
        } else {
          return( match(y, cn) )
        }
      }))
    } else {
      return(combo)
    }
  })

  names(combinations) <- sapply(combinations, function(x) {
    nm <- cn[ abs(x) ]
    nm[ x < 0 ] <- paste0("!", nm[x < 0])
    return( paste(nm[ order(abs(x)) ], collapse="&") )
  })

  return( .Call(C_COMPASS_CellCounts,
    as.list(data),
    lapply(combinations, as.integer)
  ) )
}

##' @export
CellCounts.default <- function(data, combinations) {

  if (missing(combinations)) {
    combinations <- UniqueCombinations.default(data)
  }

  if (length(unique(sapply(combinations, typeof))) > 1) {
    stop("'combinations' must all be of the same type")
  }

  output <- switch( t <- typeof(combinations[[1]]),
    double=.CellCounts_numeric(data, combinations),
    integer=.CellCounts_numeric(data, combinations),
    character=.CellCounts_character(data, combinations),
    stop ("Unexpected value type for combinations (type == ", t, ")")
  )

  return(output)


}