写一个 R function 接受一个氨基酸序列并随机返回一个密码子串

Question

使用 R，我想编写一个“反向翻译”function，它将一串氨基酸作为输入，并为每个氨基酸返回一个编码该氨基酸的三联体密码子。 密码子将从频率表中随机选择，我最初将对其值进行硬编码，但我也希望最终能够调整频率，以便更有可能选择“稀有”密码子。

到目前为止，我已经尝试使用标准 g.netic 代码中编码氨基酸的 61 个密码子来定义一个“密码子”class。

# Define codon class
codon <- function(sequence, aminoacid, frequency) {
  new_codon <- list(sequence = sequence, aminoacid = aminoacid, frequency = frequency)
  class(new_codon) <- "codon"
  new_codon
}

# Define the 61 codon frequency table
# structure: nucleotide sequence, amino acid it encodes, frequency codon is used
codons <- list(
  # Alanine (Ala) codons
  codon("GCT", "A", 0.26),
  codon("GCC", "A", 0.40),
  codon("GCA", "A", 0.23),
  codon("GCG", "A", 0.11),
  # Cysteine (Cys) codons
  codon("TGT", "C", 0.45),
  codon("TGC", "C", 0.55),
  # Aspartic acid (Asp) codons
  codon("GAT", "D", 0.46),
  codon("GAC", "D", 0.54),
  # Glutamic acid (Glu) codons
  codon("GAA", "E", 0.42),
  codon("GAG", "E", 0.58),
  # Phenylalanine (Phe) codons
  codon("TTT", "F", 0.45),
  codon("TTC", "F", 0.55),
  # Glycine (Gly) codons
  codon("GGT", "G", 0.16),
  codon("GGC", "G", 0.34),
  codon("GGA", "G", 0.25),
  codon("GGG", "G", 0.25),
  # Histidine (His) codons
  codon("CAT", "H", 0.41),
  codon("CAC", "H", 0.59),
  # Isoleucine (Ile) codons
  codon("ATT", "I", 0.36),
  codon("ATC", "I", 0.48),
  codon("ATA", "I", 0.16),
  # Lysine (Lys) codons
  codon("AAA", "K", 0.42),
  codon("AAG", "K", 0.58),
  # Leucine (Leu) codons
  codon("TTA", "L", 0.07),
  codon("TTG", "L", 0.13),
  codon("CTT", "L", 0.13),
  codon("CTC", "L", 0.20),
  codon("CTA", "L", 0.07),
  codon("CTG", "L", 0.41),
  # Methionine (Met) codon
  codon("ATG", "M", 1.0),
  # Asparagine (Asn) codons
  codon("AAT", "N", 0.46),
  codon("AAC", "N", 0.54),
  # Proline (Pro) codons
  codon("CCT", "P", 0.28),
  codon("CCC", "P", 0.33),
  codon("CCA", "P", 0.27),
  codon("CCG", "P", 0.11),
  # Glutamine (Gln) codons
  codon("CAA", "Q", 0.25),
  codon("CAG", "Q", 0.75),
  # Arginine (Arg) codons
  codon("CGT", "R", 0.08),
  codon("CGC", "R", 0.19),
  codon("CGA", "R", 0.11),
  codon("CGG", "R", 0.21),
  codon("AGA", "R", 0.20),
  codon("AGG", "R", 0.20),
  # Serine (Ser) codons
  codon("TCT", "S", 0.18),
  codon("TCC", "S", 0.22),
  codon("TCA", "S", 0.15),
  codon("TCG", "S", 0.06),
  codon("AGT", "S", 0.15),
  codon("AGC", "S", 0.24),
  # Threonine (Thr) codons
  codon("ACT", "T", 0.24),
  codon("ACC", "T", 0.36),
  codon("ACA", "T", 0.28),
  codon("ACG", "T", 0.12),
  # Valine (Val) codons
  codon("GTT", "V", 0.18),
  codon("GTC", "V", 0.24),
  codon("GTA", "V", 0.11),
  codon("GTG", "V", 0.47),
  # Tryptophan (Trp) codon
  codon("TGG", "W", 1.0),
  # Tyrosine (Tyr) codons
  codon("TAT", "Y", 0.43),
  codon("TAC", "Y", 0.57)
)

我在下面试过的 function：

# Define function to generate new sequence
random_sequence <- function(protein_sequence) {
  # Initialize empty list to store new sequence
  new_sequence <- list()
  # Iterate over each amino acid in the protein sequence
  for (aa in protein_sequence) {
    # Get all codons that encode the current amino acid
    aa_codons <- codons[sapply(codons, function(x) x$aminoacid == aa)]
    # Get the frequencies of the codons
    aa_freqs <- sapply(aa_codons, function(x) x$frequency)
    # Normalize the frequencies to sum to 1
    aa_freqs <- aa_freqs / sum(aa_freqs)
    # Select a random codon based on the frequencies
    new_codon <- aa_codons[sample(1:length(aa_codons), 1, prob = aa_freqs)]
    # Add the new codon to the new sequence
    new_sequence <- c(new_sequence, new_codon[[1]][1]$sequence)
  }
  # Return the new sequence
  new_sequence <- paste(new_sequence, collapse = "")
  return(new_sequence)
}

# Example usage
protein_sequence <- "MAVVDLKECEILHTWVFPKKKHGEARNDDCQQGKPST"
random_sequence(protein_sequence)

当我单独运行这个 function 的每一行时，我得到了我期望的结果。 另外，如果我将 protein_sequence 设置为一个字母长，它也有效。 但是，当我尝试按照写入的方式运行 function 时，我收到错误消息：

Error in sum(aa_freqs) : invalid 'type' (list) of argument

我试图通过删除归一化频率以求和为 1 次安全检查来解决此问题 ( # aa_freqs <- aa_freqs / sum(aa_freqs) 。但现在我得到了一个不同的错误：

Error in sample.int(length(x), size, replace, prob) : incorrect number of probabilities

我不确定如何解决这个错误，因为当我用一个字母测试氨基酸逐行运行 function 时，它似乎一切正常。

任何帮助或见解将不胜感激！ 非常感谢您的帮助！

Answer 1

看起来您的 function 正试图一次解析整个氨基酸序列，而不是逐个字母解析。 您可以使用strsplit或等价物将传递的字符串拆分为组成部分，然后或多或少地按照您的指示进行操作：

ReverseTranscribe <- function(protein_sequence) {
  paste(sapply(unlist(strsplit(protein_sequence, "")), function(cur_amino) {
    # Extract possible codons
    potential_matches <- codons[sapply(codons, function(x) {x$aminoacid == cur_amino})]
    # Convert to a weights table
    weights_table <- data.frame(matrix(sapply(potential_matches, unlist), ncol = 3, byrow = TRUE))
    # Weighted sample
    chosen_codon <- sample(weights_table[[1]], 1, prob = weights_table[[3]])
    return(chosen_codon)
  }), collapse = "-")
}

example <- "MAVVDLKECEILHTWVFPKKKHGEARNDDCQQGKPST"

> for (i in 1:3) {
+   print(ReverseTranscribe(example))
+ }
[1] "ATG-GCT-GTC-GTG-GAT-CTC-AAG-GAA-TGT-GAG-ATC-CTG-CAT-ACC-TGG-GTT-TTC-CCC-AAG-AAA-AAG-CAC-GGT-GAG-GCT-CGG-AAT-GAC-GAT-TGC-CAG-CAG-GGC-AAG-CCT-AGC-ACC"
[1] "ATG-GCC-GTG-GTG-GAT-CTG-AAG-GAG-TGC-GAG-ATC-CTG-CAC-ACC-TGG-GTC-TTT-CCT-AAG-AAG-AAA-CAT-GGC-GAG-GCC-CGT-AAT-GAC-GAC-TGC-CAA-CAA-GGG-AAG-CCA-TCA-ACA"
[1] "ATG-GCC-GTG-GTG-GAT-TTG-AAA-GAG-TGC-GAG-ATC-CTG-CAC-ACC-TGG-GTT-TTC-CCC-AAG-AAG-AAG-CAC-GGA-GAG-GCT-CGC-AAC-GAT-GAT-TGT-CAG-CAG-GGC-AAG-CCC-TCT-ACC"