R/get.R

In sigminer: Extract, Analyze and Visualize Mutational Signatures for Genomic Variations

# ========================================================
# internal analysis functions, use get_ as start
# ========================================================

# Get copy number list ----------------------------------------------------

get_cnlist <- function(CopyNumber, ignore_chrs = NULL, add_index = FALSE) {
  if (!inherits(CopyNumber, "CopyNumber") & !data.table::is.data.table(CopyNumber)) {
    stop("Input must be a CopyNumber object or a data.table!")
  }
  if (is.data.frame(CopyNumber)) {
    ## If it is a data.table
    # order by segment start position by each chromosome in each sample
    req_cols <- c("chromosome", "start", "end", "segVal", "sample")
    data <- data.table::copy(CopyNumber)

    if (!all(req_cols %in% colnames(data))) {
      stop(paste0(req_cols, collapse = ","), " are necessary columns!")
    }

    data <- data[, .SD[order(.SD$start, decreasing = FALSE)], by = c("sample", "chromosome")]
    all_cols <- colnames(data)
    data.table::setcolorder(data, neworder = c(req_cols, setdiff(all_cols, req_cols)))
  } else {
    data <- CopyNumber@data
  }

  if (add_index) {
    data$Index <- seq(1, nrow(data))
    send_success("Generated 'Index' column to track the copy number segment location.")
  }

  if (!is.null(ignore_chrs)) {
    chrs_exist <- ignore_chrs %in% unique(data$chromosome)
    if (!any(chrs_exist)) {
      send_info(
        "No chromosome names called ",
        paste(ignore_chrs, collapse = ","), " found in data, skipping filter."
      )
    } else {
      send_info("Filtering out segments in ", paste(ignore_chrs[chrs_exist], collapse = ","))
      data <- data[!chromosome %in% ignore_chrs[chrs_exist]]
    }
  }

  res <- split(data, by = "sample")
  res
}

# Get feature distributions -----------------------------------------------

get_features_wang <- function(CN_data,
                              cores = 1,
                              genome_build = c("hg19", "hg38", "T2T", "mm10", "mm9", "ce11"),
                              feature_setting = sigminer::CN.features) {
  genome_build <- match.arg(genome_build)
  # get chromosome lengths and centromere locations
  chrlen <- get_genome_annotation(data_type = "chr_size", genome_build = genome_build)
  centromeres <- get_genome_annotation(data_type = "centro_loc", genome_build = genome_build)

  oplan <- future::plan()
  future::plan(set_future_strategy(), workers = cores)
  on.exit(future::plan(oplan), add = TRUE)

  features <- unique(feature_setting$feature)

  .get_feature <- function(i) {
    if (i == "SS") {
      send_info("Getting (log10 based) segment size...")
      zz <- getSegsize(CN_data)
      zz$value <- log10(zz$value)
      zz
    } else if (i == "BP10MB") {
      send_info("Getting breakpoint count per 10 Mb...")
      getBPnum(CN_data, chrlen)
    } else if (i == "OsCN") {
      send_info("Getting length of chains of oscillating copy number...")
      getOscilation(CN_data)
    } else if (i == "BPArm") {
      send_info("Getting breakpoint count per chromosome arm...")
      getCentromereDistCounts(CN_data, centromeres)
    } else if (i == "CNCP") {
      send_info("Getting change-point copy number change...")
      getChangepointCN(CN_data)
    } else if (i == "CN") {
      send_info("Getting copy number...")
      getCN(CN_data)
    } else if (i == "BoChr") {
      send_info("Getting burden of chromosome...")
      getBoChr(CN_data, genome_build)
    } else if (i == "NChrV") {
      send_info("Getting number of autosome with CNV...")
      getNChrV(CN_data, genome_build)
    } else if (i == "NC50") {
      send_info("Getting the minimal number of chromosome with 50% CNV...")
      getNC50(CN_data, genome_build)
    }
  }

  res <- furrr::future_map(features, .get_feature,
    .progress = TRUE, .options = furrr::furrr_options(seed = TRUE)
  )
  res <- res %>% setNames(features)
  res
}


# Get copy number length profile ------------------------------------------

get_LengthFraction <- function(CN_data,
                               genome_build = c("hg19", "hg38", "T2T", "mm10", "mm9", "ce11"),
                               seg_cols = c("Chromosome", "Start.bp", "End.bp", "modal_cn"),
                               samp_col = "sample") {
  stopifnot(is.list(CN_data) | is.data.frame(CN_data))
  genome_build <- match.arg(genome_build)

  if (inherits(CN_data, "list")) {
    segTab <- data.table::rbindlist(CN_data, use.names = TRUE, fill = TRUE)
    # segTab = base::Reduce(rbind, CN_data)
    if (!samp_col %in% colnames(segTab)) {
      segTab$sample <- base::rep(
        x = names(CN_data),
        times = sapply(CN_data, function(x) {
          nrow(x)
        })
      )
      samp_col <- "sample"
    }
  } else {
    segTab <- CN_data
  }

  if (inherits(segTab, "data.table")) {
    segTab <- segTab[, c(seg_cols, samp_col), with = FALSE]
  } else {
    segTab <- segTab[, c(seg_cols, samp_col)]
  }

  if (ncol(segTab) == 5) {
    colnames(segTab) <- c("chromosome", "start", "end", "segVal", "sample")
  } else if (ncol(segTab) == 4) {
    colnames(segTab) <- c("chromosome", "start", "end", "sample")
  } else {
    send_stop(
      "If input is a data.frame, must have 4 necessary columns (chr, start, end, sample) and 1 optional column (segVal)."
    )
  }

  data.table::setDT(segTab)
  segTab$start <- as.numeric(segTab$start)
  segTab$end <- as.numeric(segTab$end)
  # unify chromosome column
  segTab$chromosome <- as.character(segTab$chromosome)
  segTab$chromosome <- sub(
    pattern = "chr",
    replacement = "chr",
    x = segTab$chromosome,
    ignore.case = TRUE
  )

  segTab$chromosome <- ifelse(startsWith(segTab$chromosome, "chr"),
    segTab$chromosome,
    paste0("chr", segTab$chromosome)
  )

  if (genome_build %in% c("mm10", "mm9")) {
    valid_chr <- c(paste0("chr", 1:19), "chrX", "chrY")

    if (!all(segTab$chromosome %in% valid_chr)) {
      segTab <- segTab[valid_chr, on = "chromosome"]
      send_success("Some invalid segments (not as 1:19 and X, Y) dropped.")
    }
  } else {
    valid_chr <- c(paste0("chr", 1:22), "chrX", "chrY")

    if (!all(segTab$chromosome %in% valid_chr)) {
      segTab <- segTab[valid_chr, on = "chromosome"]
      send_success("Some invalid segments (not as 1:22 and X, Y) dropped.")
    }
  }

  arm_data <- get_ArmLocation(genome_build)
  data.table::setDT(arm_data)

  segTab <- data.table::merge.data.table(segTab, arm_data, by.x = "chromosome", by.y = "chrom", all.x = TRUE)

  segTab[, flag := data.table::fifelse(
    end <= p_end & start >= p_start,
    1L,
    data.table::fifelse(
      end <= q_end & start >= q_start,
      2L,
      data.table::fifelse(
        start >= p_start & start <= p_end & end >= q_start & end <= q_end,
        3L,
        data.table::fifelse(
          start < p_end & end < q_start,
          4L,
          data.table::fifelse(
            start > p_end & start < q_start & end > q_start,
            5L,
            6L
          )
        )
      )
    )
  )]

  segTab[, location := data.table::fifelse(
    flag == 1L,
    paste0(sub("chr", "", chromosome), "p"),
    data.table::fifelse(
      flag == 2L,
      paste0(sub("chr", "", chromosome), "q"),
      data.table::fifelse(
        flag == 3L,
        paste0(sub("chr", "", chromosome), "pq"),
        data.table::fifelse(
          flag == 4L,
          paste0(sub("chr", "", chromosome), "p"),
          data.table::fifelse(
            flag == 5L,
            paste0(sub("chr", "", chromosome), "q"),
            paste0(sub("chr", "", chromosome), "pq")
          )
        )
      )
    )
  )]

  segTab[, annotation := data.table::fifelse(
    flag == 1L,
    "short arm",
    data.table::fifelse(
      flag == 2L,
      "long arm",
      data.table::fifelse(
        flag == 3L,
        "across short and long arm",
        data.table::fifelse(
          flag == 4L,
          "short arm intersect with centromere region",
          data.table::fifelse(
            flag == 5L,
            "long arm intersect with centromere region",
            "segment locate in centromere region"
          )
        )
      )
    )
  )]

  segTab[, fraction := data.table::fifelse(
    flag == 1L,
    (end - start + 1) / (p_end - p_start + 1),
    data.table::fifelse(
      flag == 2L,
      (end - start + 1) / (q_end - q_start + 1),
      data.table::fifelse(
        flag == 3L,
        2 * ((end - start + 1) / total_size),
        data.table::fifelse(
          flag == 4L,
          (end - start + 1 - (end - p_end)) / (p_end - p_start + 1),
          data.table::fifelse(
            flag == 5L,
            (end - start + 1 - (start - q_start)) / (q_end - q_start + 1),
            2 * ((end - start + 1) / total_size)
          )
        )
      )
    )
  )]

  segTab[, c(colnames(arm_data)[-1], "flag") := NULL]
  segTab

}


# Get arm location --------------------------------------------------------

get_ArmLocation <- function(genome_build = c("hg19", "hg38", "T2T", "mm10", "mm9", "ce11")) {
  genome_build <- match.arg(genome_build)
  # get chromosome lengths and centromere locations
  chrlen <- get_genome_annotation(data_type = "chr_size", genome_build = genome_build)
  centromeres <- get_genome_annotation(data_type = "centro_loc", genome_build = genome_build)

  l <- nrow(chrlen)
  # compute and get results
  # different for human and mouse
  res <- data.frame(
    chrom = vector(mode = "character", length = l),
    p_start = vector("numeric", length = l),
    p_end = vector("numeric", length = l),
    p_length = vector("numeric", length = l),
    q_start = vector("numeric", length = l),
    q_end = vector("numeric", length = l),
    q_length = vector("numeric", length = l),
    total_size = vector("numeric", length = l),
    stringsAsFactors = FALSE
  )

  i <- 1
  for (chr in chrlen$chrom) {
    chrom <- chr

    # p
    p_start <- 1
    p_end <- centromeres$left.base[centromeres$chrom == chr]
    p_length <- p_end - p_start + 1

    # q
    q_start <- centromeres$right.base[centromeres$chrom == chr]
    q_end <- chrlen$size[chrlen$chrom == chr]
    q_length <- q_end - q_start + 1

    total_size <- chrlen$size[chrlen$chrom == chr]

    res[i, 1] <- as.character(chrom)
    res[i, 2:8] <- c(
      p_start,
      p_end,
      p_length,
      q_start,
      q_end,
      q_length,
      total_size
    )
    i <- i + 1
  }

  res
}

# Get summary of copy number variation per sample ------------------------------------

get_cnsummary_sample <- function(segTab, genome_build = c("hg19", "hg38", "T2T", "mm10", "mm9", "ce11"),
                                 genome_measure = c("called", "wg")) {
  genome_build <- match.arg(genome_build)
  genome_measure <- match.arg(genome_measure)

  # "Input must have 5 ordered columns (chr, start, end, segVal, sample)."
  # colnames(segTab)[1:5] <- c("chromosome", "start", "end", "segVal", "sample")

  # Handle sex
  sex <- getOption("sigminer.sex", default = "female")
  if (is.character(sex)) {
    if (sex == "male") {
      segTab <- segTab %>%
        dplyr::as_tibble() %>%
        dplyr::mutate(
          segVal = ifelse(.data$chromosome %in% c("chrX", "chrY"), 2L * .data$segVal, .data$segVal)
        ) %>%
        data.table::as.data.table()
    }
  }
  if (is.data.frame(sex)) {
    segTab <- segTab %>%
      dplyr::as_tibble() %>%
      dplyr::left_join(sex, by = "sample") %>%
      dplyr::mutate(
        segVal = dplyr::case_when(
          .data$sex == "male" & .data$chromosome %in% c("chrX", "chrY") ~ 2L * .data$segVal,
          TRUE ~ .data$segVal
        )
      ) %>%
      dplyr::select(-"sex") %>%
      dplyr::select(c("chromosome", "start", "end", "segVal", "sample"), dplyr::everything()) %>%
      data.table::as.data.table()
  }

  data.table::setDT(segTab)
  segTab$start <- as.numeric(segTab$start)
  segTab$end <- as.numeric(segTab$end)

  if (genome_build %in% c("mm10", "mm9")) {
    autosome <- paste0("chr", 1:19)
  } else {
    autosome <- paste0("chr", 1:22)
  }

  if (genome_measure == "wg") {
    chrlen <- get_genome_annotation(
      data_type = "chr_size",
      chrs = autosome,
      genome_build = genome_build
    )
    total_size <- sum(chrlen[["size"]])

    seg_sum1 <- segTab %>%
      dplyr::as_tibble() %>%
      dplyr::group_by(.data$sample) %>%
      dplyr::summarise(
        n_of_seg = sum(!is.na(segVal)),
        n_of_cnv = sum(segVal != 2),
        n_of_amp = sum(segVal > 2),
        n_of_del = sum(segVal < 2)
      )

    if ("loh" %in% colnames(segTab)) {
      seg_sum2 <- segTab %>%
        dplyr::as_tibble() %>%
        dplyr::filter(chromosome %in% autosome) %>%
        dplyr::group_by(.data$sample) %>%
        dplyr::summarise(
          n_of_vchr = length(unique(chromosome[segVal != 2])),
          n_loh = sum(.data$loh, na.rm = TRUE),
          cna_burden = sum(end[segVal != 2] - start[segVal != 2] + 1) / total_size
        )
    } else {
      seg_sum2 <- segTab %>%
        dplyr::as_tibble() %>%
        dplyr::filter(chromosome %in% autosome) %>%
        dplyr::group_by(.data$sample) %>%
        dplyr::summarise(
          n_of_vchr = length(unique(chromosome[segVal != 2])),
          cna_burden = sum(end[segVal != 2] - start[segVal != 2] + 1) / total_size
        )
    }

    seg_summary <- dplyr::full_join(seg_sum1, seg_sum2, by = "sample") %>%
      data.table::as.data.table()
  } else {
    seg_sum1 <- segTab %>%
      dplyr::as_tibble() %>%
      dplyr::group_by(.data$sample) %>%
      dplyr::summarise(
        n_of_seg = sum(!is.na(segVal)),
        n_of_cnv = sum(segVal != 2),
        n_of_amp = sum(segVal > 2),
        n_of_del = sum(segVal < 2)
      )

    if ("loh" %in% colnames(segTab)) {
      seg_sum2 <- segTab %>%
        dplyr::as_tibble() %>%
        dplyr::filter(chromosome %in% autosome) %>%
        dplyr::group_by(.data$sample) %>%
        dplyr::summarise(
          n_of_vchr = length(unique(chromosome[segVal != 2])),
          n_loh = sum(.data$loh, na.rm = TRUE),
          cna_burden = sum(end[segVal != 2] - start[segVal != 2] + 1) / sum(end - start + 1)
        )
    } else {
      seg_sum2 <- segTab %>%
        dplyr::as_tibble() %>%
        dplyr::filter(chromosome %in% autosome) %>%
        dplyr::group_by(.data$sample) %>%
        dplyr::summarise(
          n_of_vchr = length(unique(chromosome[segVal != 2])),
          cna_burden = sum(end[segVal != 2] - start[segVal != 2] + 1) / sum(end - start + 1)
        )
    }

    seg_summary <- dplyr::full_join(seg_sum1, seg_sum2, by = "sample") %>%
      data.table::as.data.table()
  }

  seg_summary <- seg_summary[order(seg_summary$n_of_cnv)]
  seg_summary$cna_burden <- round(seg_summary$cna_burden, 3)
  attr(seg_summary, "Note") <- "n_of_vchr is the number of autosome with CNV.\n cna_burden also calculates from autosome."
  seg_summary
}

# Classify copy number features into components ------------------------------------
# Automatically handle and support official/custom copy number feature classfication setting

get_feature_components <- function(x) {
  stopifnot(is.data.frame(x), all(c("feature", "min", "max") %in% colnames(x)))

  x <- x %>%
    dplyr::mutate(
      component = dplyr::case_when(
        .data$min == .data$max ~ sprintf("%s[%s]", .data$feature, .data$min),
        is.infinite(.data$min) ~ sprintf("%s[<=%s]", .data$feature, .data$max),
        is.infinite(.data$max) ~ sprintf("%s[>%s]", .data$feature, .data$min),
        .data$max > .data$min ~ sprintf("%s[>%s & <=%s]", .data$feature, .data$min, .data$max),
        TRUE ~ NA_character_
      ),
      label = ifelse(.data$min == .data$max, "point", "range")
    ) %>%
    data.table::as.data.table()

  x <- x[, c("feature", "component", "label", "min", "max")]

  if (any(is.na(x$component))) {
    stop("Result componet column contain NAs, please check your input!")
  } else {
    class(x) <- c(class(x), "sigminer.features")
    return(x)
  }
}

# Global variables --------------------------------------------------------

utils::globalVariables(
  c(
    "i",
    "chrom",
    "chromosome",
    "segVal",
    ".SD"
  )
)