# This code is part of the Biopython distribution and governed by its
# license.  Please see the LICENSE file that should have been included
# as part of this package.
#

from __future__ import print_function

import math
from .CodonUsageIndices import SharpEcoliIndex
from Bio import SeqIO # To parse a FASTA file


CodonsDict = {'TTT': 0, 'TTC': 0, 'TTA': 0, 'TTG': 0, 'CTT': 0,
'CTC': 0, 'CTA': 0, 'CTG': 0, 'ATT': 0, 'ATC': 0,
'ATA': 0, 'ATG': 0, 'GTT': 0, 'GTC': 0, 'GTA': 0,
'GTG': 0, 'TAT': 0, 'TAC': 0, 'TAA': 0, 'TAG': 0,
'CAT': 0, 'CAC': 0, 'CAA': 0, 'CAG': 0, 'AAT': 0,
'AAC': 0, 'AAA': 0, 'AAG': 0, 'GAT': 0, 'GAC': 0,
'GAA': 0, 'GAG': 0, 'TCT': 0, 'TCC': 0, 'TCA': 0,
'TCG': 0, 'CCT': 0, 'CCC': 0, 'CCA': 0, 'CCG': 0,
'ACT': 0, 'ACC': 0, 'ACA': 0, 'ACG': 0, 'GCT': 0,
'GCC': 0, 'GCA': 0, 'GCG': 0, 'TGT': 0, 'TGC': 0,
'TGA': 0, 'TGG': 0, 'CGT': 0, 'CGC': 0, 'CGA': 0,
'CGG': 0, 'AGT': 0, 'AGC': 0, 'AGA': 0, 'AGG': 0,
'GGT': 0, 'GGC': 0, 'GGA': 0, 'GGG': 0}


# this dictionary shows which codons encode the same AA
SynonymousCodons = {
    'CYS': ['TGT', 'TGC'],
    'ASP': ['GAT', 'GAC'],
    'SER': ['TCT', 'TCG', 'TCA', 'TCC', 'AGC', 'AGT'],
    'GLN': ['CAA', 'CAG'],
    'MET': ['ATG'],
    'ASN': ['AAC', 'AAT'],
    'PRO': ['CCT', 'CCG', 'CCA', 'CCC'],
    'LYS': ['AAG', 'AAA'],
    'STOP': ['TAG', 'TGA', 'TAA'],
    'THR': ['ACC', 'ACA', 'ACG', 'ACT'],
    'PHE': ['TTT', 'TTC'],
    'ALA': ['GCA', 'GCC', 'GCG', 'GCT'],
    'GLY': ['GGT', 'GGG', 'GGA', 'GGC'],
    'ILE': ['ATC', 'ATA', 'ATT'],
    'LEU': ['TTA', 'TTG', 'CTC', 'CTT', 'CTG', 'CTA'],
    'HIS': ['CAT', 'CAC'],
    'ARG': ['CGA', 'CGC', 'CGG', 'CGT', 'AGG', 'AGA'],
    'TRP': ['TGG'],
    'VAL': ['GTA', 'GTC', 'GTG', 'GTT'],
    'GLU': ['GAG', 'GAA'],
    'TYR': ['TAT', 'TAC']
}


class CodonAdaptationIndex(object):
    """A codon adaptation index (CAI) implementation.

    Implements the codon adaptation index (CAI) described by Sharp and
    Li (Nucleic Acids Res. 1987 Feb 11;15(3):1281-95).

    NOTE - This implementation does not currently cope with alternative genetic
    codes: only the synonymous codons in the standard table are considered.
    """

    def __init__(self):
        self.index = {}
        self.codon_count = {}

    # use this method with predefined CAI index
    def set_cai_index(self, index):
        """Sets up an index to be used when calculating CAI for a gene.
        Just pass a dictionary similar to the SharpEcoliIndex in the
        CodonUsageIndices module.
        """
        self.index = index

    def generate_index(self, fasta_file):
        """Generate a codon usage index from a FASTA file of CDS sequences.

        Takes a location of a Fasta file containing CDS sequences
        (which must all have a whole number of codons) and generates a codon
        usage index.
        """

        # first make sure we're not overwriting an existing index:
        if self.index != {} or self.codon_count != {}:
            raise ValueError("an index has already been set or a codon count has been done. cannot overwrite either.")

        # count codon occurrences in the file.
        self._count_codons(fasta_file)

        # now to calculate the index we first need to sum the number of times
        # synonymous codons were used all together.
        for aa in SynonymousCodons:
            total = 0.0
            rcsu = []  # RCSU values are CodonCount/((1/num of synonymous codons) * sum of all synonymous codons)
            codons = SynonymousCodons[aa]

            for codon in codons:
                total += self.codon_count[codon]

            # calculate the RSCU value for each of the codons
            for codon in codons:
                denominator = float(total) / len(codons)
                rcsu.append(self.codon_count[codon] / denominator)

            # now generate the index W=RCSUi/RCSUmax:
            rcsu_max = max(rcsu)
            for i in range(len(codons)):
                self.index[codons[i]] = rcsu[i] / rcsu_max

    def cai_for_gene(self, dna_sequence):
        """Calculate the CAI (float) for the provided DNA sequence (string).

        This method uses the Index (either the one you set or the one you generated)
        and returns the CAI for the DNA sequence.
        """
        cai_value, cai_length = 0, 0

        # if no index is set or generated, the default SharpEcoliIndex will be used.
        if self.index == {}:
            self.set_cai_index(SharpEcoliIndex)

        if dna_sequence.islower():
            dna_sequence = dna_sequence.upper()

        for i in range(0, len(dna_sequence), 3):
            codon = dna_sequence[i:i+3]
            if codon in self.index:
                if codon not in ['ATG', 'TGG']:  # these two codons are always one, exclude them
                    cai_value += math.log(self.index[codon])
                    cai_length += 1
            elif codon not in ['TGA', 'TAA', 'TAG']:  # some indices may not include stop codons
                raise TypeError("illegal codon in sequence: %s.\n%s" % (codon, self.index))

        return math.exp(cai_value / (cai_length - 1.0))

    def _count_codons(self, fasta_file):
        with open(fasta_file, 'r') as handle:

            # make the codon dictionary local
            self.codon_count = CodonsDict.copy()

            # iterate over sequence and count all the codons in the FastaFile.
            for cur_record in SeqIO.parse(handle, "fasta"):
                # make sure the sequence is lower case
                if str(cur_record.seq).islower():
                    dna_sequence = str(cur_record.seq).upper()
                else:
                    dna_sequence = str(cur_record.seq)
                for i in range(0, len(dna_sequence), 3):
                    codon = dna_sequence[i:i+3]
                    if codon in self.codon_count:
                        self.codon_count[codon] += 1
                    else:
                        raise TypeError("illegal codon %s in gene: %s" % (codon, cur_record.id))

    # this just gives the index when the objects is printed.
    def print_index(self):
        """Prints out the index used."""
        for i in sorted(self.index):
            print("%s\t%.3f" % (i, self.index[i]))
