from Bio.PDB import PDBParser
from Bio.SeqUtils import seq1
import PANDORA
from PANDORA.Contacts import Contacts
from PANDORA.Database import Database_functions
from PANDORA.Pandora import Modelling_functions
from PANDORA.PMHC import Anchors
from abc import ABC, abstractmethod
import os
[docs]class PMHC(ABC):
def __init__(self, id, allele_type, peptide = '', MHC_class = 'I', M_chain_seq = '', N_chain_seq = '', anchors = [],
helix=False, sheet=False):
''' pMHC class. Acts as a parent class to Template and Target
Args:
id: (string) PDB identifier
allele_type: (list) list of MHC alleles (or allele)
peptide: (string) peptide sequence
MHC_class: (string) either 'I' or 'II' denoting MHC class I and MHC class II respectively
M_chain_seq: (string) M chain sequence for the Alpha chain
N_chain_seq: (string) N chain sequence for the Beta chain
anchors: (list) list of integers specifying which residue(s) of the peptide should be fixed as an anchor
during the modelling. MHC class I typically has 2 anchors, while MHC class II typically has 4.
'''
super().__init__()
self.id = id
self.MHC_class = MHC_class
self.peptide = peptide
self.M_chain_seq = M_chain_seq
self.N_chain_seq = N_chain_seq
self.allele_type = allele_type
self.anchors = anchors
self.helix = helix
self.sheet = sheet
@abstractmethod
def info(self):
pass
@abstractmethod
def calc_contacts(self):
pass
@abstractmethod
def calc_anchor_contacts(self):
pass
[docs]class Template(PMHC):
def __init__(self, id, allele_type, peptide='', MHC_class='I', M_chain_seq='', N_chain_seq='', anchors=[], helix=False, sheet=False, pdb_path=False, pdb=False, resolution=None):
''' Template structure class. This class holds all information of a template structure that is used for
homology modelling. This class needs a id, allele and the path to a pdb file to work. (sequence info of
the chains and peptide can be fetched from the pdb)
Args:
id: (string) PDB identifier
allele_type: (list) list of MHC alleles (or allele)
peptide: (string) peptide sequence
MHC_class: (string) either 'I' or 'II' denoting MHC class I and MHC class II respectively
M_chain_seq: (string) M chain sequence for the Alpha chain
N_chain_seq: (string) N chain sequence for the Beta chain
anchors: (list) list of integers specifying which residue(s) of the peptide should be fixed as an anchor
during the modelling. MHC class I typically has 2 anchors, while MHC class II typically has 4.
pdb_path: (string) path to pdb file
pdb: (Bio.PDB) Biopython PBD object
resolution: (float) Structure resolution in Angstrom
'''
super().__init__(id, allele_type, peptide, MHC_class, M_chain_seq, N_chain_seq, anchors, helix, sheet)
self.pdb_path = pdb_path
self.pdb = pdb
self.contacts = False
self.resolution = resolution
if not pdb_path and not pdb:
raise Exception('Provide a PDB structure to the Template object first')
if pdb_path and not pdb: # If the path to a pdb file or a Bio.PDB object is given, parse the pdb
self.parse_pdb()
if anchors == []:
self.calc_anchors()
[docs] def parse_pdb(self):
'''Loads pdb from path, updates self.pdb field and self.chain_seq/self.peptide if they were empty'''
if self.pdb_path and not self.pdb: #if there is a path to a pdb provided and there is not already a self.pdb...
parser = PDBParser(QUIET=True) # Create a parser object, used to read pdb files
self.pdb = parser.get_structure('MHC', self.pdb_path) #Create Bio.PDB object
self.resolution = Database_functions.get_resolution(self.pdb_path) #Get resolution from pdb file
# If the chains or peptide are not given by the user, fetch them from the pdb
# Get the chain sequences
chain_seqs = [seq1(''.join([res.resname for res in chain])) for chain in self.pdb.get_chains()]
# Update chain and peptide fields if emtpy
if self.MHC_class == 'I':
if self.M_chain_seq == '':
self.M_chain_seq = chain_seqs[0]
if not self.peptide:
self.peptide = chain_seqs[-1]
if self.MHC_class == 'II':
if self.M_chain_seq == '' and self.N_chain_seq == '':
self.M_chain_seq = chain_seqs[0]
self.N_chain_seq = chain_seqs[1]
if not self.peptide:
self.peptide = chain_seqs[-1]
[docs] def info(self):
""" Print the basic info of this structure
"""
print('This is a %s structure.' %(type(self).__name__))
print('ID: %s' %self.id)
print('Type: MHC class %s' %self.MHC_class)
print('Alleles: %s' % self.allele_type)
if self.M_chain_seq != '':
print('Alpha chain length: %s' %len(self.M_chain_seq))
if self.N_chain_seq != '' and self.MHC_class == 'II':
print('Beta chain length: %s' %len(self.N_chain_seq))
print('Peptide length: %s' %len(self.peptide))
if self.M_chain_seq != '':
print('Alpha chain: %s' % self.M_chain_seq)
if self.N_chain_seq != '':
print('Beta chain: %s' % self.N_chain_seq)
print('Peptide: %s' % self.peptide)
print('Anchors: %s' %self.anchors)
if self.sheet:
print('Beta-sheet: %s' % self.sheet)
if self.helix:
print('Alpha-helix: %s' % self.helix)
if self.pdb_path:
print('Path to PDB file: %s' %self.pdb_path)
if not self.pdb:
print('PDB structure: no PDB structure provided')
else:
print('PDB structure:')
for (k, v) in self.pdb.header.items():
print('\t'+k + ':', v)
[docs] def calc_anchors(self):
if self.MHC_class == 'I':
self.anchors = Anchors.pMHCI_anchors(self.pdb)
if self.MHC_class == 'II':
self.anchors = Anchors.pMHCII_anchors(self.pdb)
[docs]class Target(PMHC):
def __init__(self, id, allele_type, peptide, MHC_class = 'I', M_chain_seq = '', N_chain_seq = '', anchors = [],
helix=False, sheet=False, templates = False, use_netmhcpan = False):
''' Target structure class. This class needs an ID (preferably a PDB ID), allele and pepide information.
Args:
id: (string) PDB identifier
peptide: (string) peptide sequence
allele_type: (list) list of MHC alleles (or allele)
MHC_class: (string) either 'I' or 'II' denoting MHC class I and MHC class II respectively
M_chain_seq: (string) M chain sequence for the Alpha chain
N_chain_seq: (string) N chain sequence for the Beta chain
anchors: (list) list of integers specifying which residue(s) of the peptide should be fixed as an anchor
during the modelling. MHC class I typically has 2 anchors, while MHC class II typically has 4.
templates: Template object. The user can specify that PANDORA uses a certain structure as template.
use_netmhcpan (bool): If True, uses local installation of NetMHCPan to predict the anchors when
anchor positions are not provided. Defaults to False.
'''
super().__init__(id, allele_type, peptide, MHC_class, M_chain_seq, N_chain_seq, anchors, helix, sheet)
self.templates = templates
self.initial_model = False
self.contacts = False
self.anchor_contacts = False
# If the user does provide sequence info, make sure both the M and N chain are provided
if MHC_class == 'II' and M_chain_seq != '' and N_chain_seq == '':
raise Exception('Provide both the M and N chain sequences for MHC class II targets or none at all')
if MHC_class == 'II' and N_chain_seq != '' and M_chain_seq == '':
raise Exception('Provide both the M and N chain sequences for MHC class II targets or none at all')
# If the user does not provide sequence info, retrieve them from the reference sequences.
# WARNING: currently available only for MHC I
if MHC_class == 'I' and M_chain_seq =='':
print('No MHC sequence was provided. Trying to retrieve it from reference sequences...')
try:
self.retrieve_MHCI_refseq()
except:
print('Something went wrong while retrieving the reference sequence.')
print('Please provide a M_chain_seq for your target.')
print('###################')
print('You can find all the reference MHC sequences used in PANDORA')
print(' and use them for your target in <MyDatabase>.ref_MHCI_sequences')
print('Where <MyDatabase> is the name of your PANDORA Database object.')
print('###################')
print('You can also find reference MHC sequences for Humans at:')
print('https://www.ebi.ac.uk/ipd/imgt/hla/')
print('And for other animals here:')
print('https://www.ebi.ac.uk/ipd/mhc/')
print('###################')
raise Exception('Failed in retriving reference sequence.')
elif MHC_class == 'II' and M_chain_seq =='' and N_chain_seq =='':
print('No MHC sequence was provided. Trying to retrieve it from reference sequences...')
raise Exception('Reference MHC II sequences have not been implemented yet. Please provide both M and N chain sequence.')
# If anchors are not provided, predict them from the peptide length
if MHC_class =='I' and anchors == []:
#Use Canonical anchors
if use_netmhcpan == False:
print('WARNING: no anchor positions provided. Pandora will assign them to canonical anchor position.')
print('If you want PANDORA to use NetMHCpan to predict the anchors set use_netmhcpan as True')
anchor_1 = 2
anchor_2 = len(peptide)
anchors = [anchor_1, anchor_2]
self.anchors = anchors
#Use NetMHCpan to predict the anchors
else:
print('WARNING: no anchor positions provided. Pandora will predict them using NetMHCpan')
netMHCpan_dir = [i for i in os.listdir(PANDORA.PANDORA_path + '/../') if
i.startswith('netMHCpan') and os.path.isdir(PANDORA.PANDORA_path + '/../'+i)]
if os.path.isfile(PANDORA.PANDORA_path + '/../' + netMHCpan_dir[0] + '/netMHCpan'):
# predict the anchors
self.anchors = Modelling_functions.predict_anchors_netMHCpan(self.peptide, self.allele_type)
print('Predicted anchors: %s' %self.anchors)
else:
print("Need netMHCIIpan to predict anchor positions. Please download and install netMHCpan.\n\n"
"The user needs to manually download the netMHCIIpan software, since it requires agreement to an academic license agreement.\n"
"1. Go to: https://services.healthtech.dtu.dk/service.php?NetMHCpan-4.1\n"
"2. press the download button\n"
"3. Download the most recent version appropriate for your operating system\n"
"4. Untar the file and put it in the root directory of your PANDORA install\n"
"5. Follow the readme or simply run netMHCpan_install.py to configure netMHCpan")
if MHC_class =='II' and anchors == []:
print('WARNING: no anchor positions provided. Pandora will predict them using netMHCIIpan.')
netMHCIIpan_dir = [i for i in os.listdir(PANDORA.PANDORA_path + '/../') if
i.startswith('netMHCIIpan') and os.path.isdir(PANDORA.PANDORA_path + '/../'+i)]
if os.path.isfile(PANDORA.PANDORA_path + '/../' + netMHCIIpan_dir[0] + '/netMHCIIpan'):
# predict the anchors
self.anchors = Modelling_functions.predict_anchors_netMHCIIpan(self.peptide, self.allele_type)
else:
print("Need netMHCpan to predict anchor positions. Please download and install netMHCIIpan.\n\n"
"The user needs to manually download the netMHCpan software, since it requires agreement to an academic license agreement.\n"
"1. Go to: https://services.healthtech.dtu.dk/service.php?NetMHCpan-4.1\n"
"2. press the download button\n"
"3. Download the most recent version appropriate for your operating system\n"
"4. Untar the file and put it in the root directory of your PANDORA install\n"
"5. Follow the readme or simply run netMHCpan_install.py to configure netMHCIIpan")
[docs] def info(self):
""" Print the basic info of this structure
"""
print('This is a %s structure.' % (type(self).__name__))
print('ID: %s' % self.id)
print('Type: MHC class %s' % self.MHC_class)
print('Alleles: %s' % self.allele_type)
if self.M_chain_seq != '':
print('Alpha chain length: %s' %len(self.M_chain_seq))
if self.N_chain_seq != '' and self.MHC_class == 'II':
print('Beta chain length: %s' %len(self.N_chain_seq))
print('Peptide length: %s' %len(self.peptide))
if self.M_chain_seq != '':
print('Alpha chain: %s' % self.M_chain_seq)
if self.N_chain_seq != '':
print('Beta chain: %s' % self.N_chain_seq)
print('Peptide: %s' % self.peptide)
print('Anchors: %s' % self.anchors)
if self.sheet:
print('Beta-sheet: %s' % self.sheet)
if self.helix:
print('Alpha-helix: %s' % self.helix)
if self.templates:
print('Using template %s for homology modelling' %self.templates)
if self.initial_model:
print('An initial model has been provided.')
[docs] def retrieve_MHCI_refseq(self, input_file = None):
"""
Retrieves MHC I reference sequence from fasta file.
Args:
input_file (str, optional): Path to the input reference fasta file. Defaults to None.
Returns:
None.
"""
# Import necessary package
from Bio import SeqIO
# Define correct fasta file
if input_file == None:
if self.allele_type[0].startswith('HLA'):
input_file = PANDORA.PANDORA_data+ '/csv_pkl_files/Human_MHC_data.fasta'
else:
input_file = PANDORA.PANDORA_data+ '/csv_pkl_files/NonHuman_MHC_data.fasta'
# Parse Fasta file
fasta_sequences = SeqIO.parse(input_file,'fasta')
# Return the right sequences
seq_flag = False
for seq in fasta_sequences:
if seq.id == self.allele_type[0]:
self.M_chain_seq = str(seq.seq)
seq_flag = True
break
else:
pass
if seq_flag == True:
print('MHC sequence correctly retrieved')
else:
print('WARNING: No MHC seq could be retrieved with the given MHC allele name')
print("The model will be generated using the best template's MHC sequence.")
print("To be sure you use the right sequence, please double check your MHC allele name")
print("Or provide the MHC sequence as target.M_chain_seq")