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#!/usr/bin/python3
# encoding: utf-8
from __future__ import (absolute_import, division,
print_function, unicode_literals)
import os, sys, re
import logging
import argparse
import collections
import numpy
import time
import TGraph
import TNode
import Node_path
import Node_alignment
from GraphCycleException import GraphCycleException
import Topological_sort
import DP_matrix
logger = logging.getLogger(__name__)
logger.addHandler(logging.NullHandler())
class Gene_splice_modeler:
"""
Builds supertranscipts.
object instance members:
gene_id : str
alignments : list of Node_alignment objects
"""
def __init__(self, gene_id, node_path_obj_list):
"""
initialize alignments list with simple single 'alignment' objects with
each path as an individual alignment with just its path nodes.
params:
gene_id : str
node_path_obj_list : list of Node_path objects, each Node_path corresponding to an individual Trinity isoform
"""
self.gene_id = gene_id
self.alignments = list()
logger.debug("Gene_splice_modeler inputs: {}".format(node_path_obj_list))
for node_path_obj in node_path_obj_list:
transcript_name = node_path_obj.get_transcript_name()
alignment_obj = Node_alignment.Node_alignment.get_single_seq_node_alignment(node_path_obj)
self.alignments.append(alignment_obj)
def get_gene_id(self):
return self.gene_id
def build_splice_model(self):
"""
method to construct the super transcript.
Tries 2 approaches:
a. If there isn't an obvious repetitive node structure and so the graph formas a DAG,
we build a splice graph and perform topological sorting of the nodes.
b. If there is some repetitive structure, we resort to performing a multiple alignment-based method to
organize relationships among nodes in isoforms, and the multiple alignment produces the linear ordering
for the supertranscript.
"""
if not self.alignment_contains_repeat_node():
# no obvious cycles
try:
return self.topological_order_splice_model()
except GraphCycleException:
# have a more complex cycle here...
# try again w/ mult align approach.
return self.multiple_alignment_splice_model()
else:
return self.multiple_alignment_splice_model()
def alignment_contains_repeat_node(self):
for alignment in self.alignments:
loc_ids = set()
for i in range(0, alignment.width()):
node_obj = alignment.get_representative_column_node(i)
loc_id = node_obj.get_loc_id()
if loc_id in loc_ids:
return True
loc_ids.add(loc_id)
return False
def topological_order_splice_model(self):
"""
Build supertranscript using simpler topological sorting of the nodes.
"""
logger.debug("\tusing topological sort method.\n");
gene_id = self.get_gene_id()
## make a generic graph.
graph = TGraph.TGraph(gene_id)
for alignment in self.alignments:
logger.debug("topological_order_splice_model, input alignment: " + str(alignment))
node_list = alignment.get_aligned_nodes()[0] # should be unaligned here, so just ordered path list.
transcript_name = alignment.get_transcript_names()[0]
logger.debug("topological_order_splice_model, node list: " + str(node_list))
for i in range(0, len(node_list)):
node_obj = node_list[i]
loc_id = node_obj.get_loc_id()
generic_node = graph.get_node(transcript_name, loc_id, node_obj.get_seq()) # rely on Node class caching system
logger.debug("generic node: " + str(generic_node))
if i > 0:
# set prev node info
prev_node_obj = node_list[i-1]
prev_generic_node = graph.get_node(transcript_name, prev_node_obj.get_loc_id(), prev_node_obj.get_seq())
generic_node.add_prev_node(prev_generic_node)
if i < len(node_list) - 1:
next_node_obj = node_list[i+1]
next_generic_node = graph.get_node(transcript_name, next_node_obj.get_loc_id(), next_node_obj.get_seq())
generic_node.add_next_node(next_generic_node)
logger.debug("Before sorting nodes: " + str(graph))
topologically_sorted_nodes = Topological_sort.Topological_sort.topologically_sort(graph.get_all_nodes())
logger.debug("Topologically sorted nodes: " + str(topologically_sorted_nodes))
# index loc node ids
aligned_loc_id_pos = dict()
for i in range(0, len(topologically_sorted_nodes)):
loc_id = topologically_sorted_nodes[i].get_loc_id()
aligned_loc_id_pos[loc_id] = i
new_alignments = list()
transcript_ids = list()
for alignment in self.alignments:
transcript_ids.append(alignment.get_transcript_names()[0]) # really should only be one here.
new_alignment = [None for i in topologically_sorted_nodes]
for node in alignment.get_aligned_nodes()[0]:
loc_id = node.get_loc_id()
new_idx = aligned_loc_id_pos[loc_id]
new_alignment[new_idx] = node
new_alignments.append(new_alignment)
splice_graph_model = Node_alignment.Node_alignment(gene_id, transcript_ids, new_alignments)
logger.debug("Splice graph model: " + str(splice_graph_model))
return splice_graph_model
def multiple_alignment_splice_model(self):
"""
Multiple alignment algorithm for dealing with repeat nodes:
For each best matching pair of transcripts (or aligned transcripts),
perform alignment, and replace aligned pair with a single alignment object.
"""
logger.debug("\tusing mult alignment method.\n");
alignments = self.alignments
if len(alignments) == 1:
# no alignment is necessary.
return alignments[0]
# determine initial path similarity
similarity_matrix = Gene_splice_modeler.compute_similarity_matrix(self.alignments)
logger.debug("Similarity matrix:\n" + str(similarity_matrix))
## build multiple alignment in a hierarchical way
while len(similarity_matrix) > 1:
# set diag to -1 to avoid any zero ties w/ self-vals
for i in range(0,len(alignments)):
similarity_matrix[ i ][ i ] = -1
## find best pair
best_pair_idx = int(numpy.argmax(similarity_matrix))
num_alignments = len(similarity_matrix)
best_pair_idx_1 = int(best_pair_idx / num_alignments)
best_pair_idx_2 = best_pair_idx % num_alignments
## merge pair into single alignment
align_a = alignments[ best_pair_idx_1 ]
align_b = alignments[ best_pair_idx_2 ]
align_merged = Gene_splice_modeler.merge_alignments(align_a, align_b)
## recompute matrix
new_alignment_list = list()
for i in range(0, len(alignments)):
if i not in (best_pair_idx_1, best_pair_idx_2):
new_alignment_list.append(alignments[ i ])
new_alignment_list.append(align_merged)
alignments = new_alignment_list
logger.debug("\nUpdated alignments:\n" + str(alignments))
similarity_matrix = Gene_splice_modeler.compute_similarity_matrix(alignments)
logger.debug("Similarity matrix:\n" + str(similarity_matrix))
if len(alignments) > 1:
raise RuntimeError("Error, should only have one alignment but have {} alignments after merge".format(len(alignments)))
return alignments[0]
@staticmethod
def compute_similarity_matrix(alignments_list):
"""
similarity matrix indicates number of shared nodes between each pair of isoforms.
"""
num_alignments = len(alignments_list)
sim_matrix = numpy.zeros( (num_alignments, num_alignments), dtype='int_' )
for i in range(0, num_alignments-1):
align_i = alignments_list[i]
for j in range(i+1, num_alignments):
align_j = alignments_list[j]
common_nodes = Node_alignment.Node_alignment.compute_number_common_nodes(align_i, align_j)
num_common_nodes = len(common_nodes)
sim_matrix[ i ][ j ] = num_common_nodes
return sim_matrix
@staticmethod
def merge_alignments(align_a, align_b):
"""
Computes a mismatch-free multiple alignment (just matches and gaps) between two Node_alignment objects
returns single Node_alignment object containing the contents of aligned align_a and align_b as aligned.
"""
logger.debug("Merging alignments {} and {}".format(align_a, align_b))
## ensure the transcripts are disjoint
transcript_names_align_A = set(align_a.get_transcript_names())
transcript_names_align_B = set(align_b.get_transcript_names())
if not set.isdisjoint(transcript_names_align_A, transcript_names_align_B):
raise RuntimeError("Error, transcripts in alignments to merge are not disjoint: {} and {}".format(transcript_names_align_A, transcript_names_align_B))
width_a = align_a.width()
width_b = align_b.width()
# do global alignments w/o penalizing end gaps
dp_matrix = DP_matrix.DP_matrix.build_DP_matrix(width_a, width_b)
# put align B across top (cols) and align A at side (row)
# init the matrix zero rows
for i in range(1, width_a+1):
dp_matrix[ i ][ 0 ]['bt'] = 'DEL_B' # UP
for j in range(1, width_b+1):
dp_matrix[ 0 ][ j ]['bt'] = 'DEL_A' # LEFT
# score the DP matrix
for i in range(1, width_a+1):
for j in range(1, width_b+1):
score_cell_match = Gene_splice_modeler.get_match_score(align_a, i-1, align_b, j-1) # score matrix is 1-based, align is 0-based
score_diag = dp_matrix[ i-1 ][ j-1 ]['score'] + score_cell_match
score_del_a = dp_matrix[ i ][ j-1 ]['score']
score_del_b = dp_matrix[ i-1 ][ j ]['score']
if score_cell_match > 0 and score_diag >= score_del_a and score_diag >= score_del_b:
dp_matrix[ i ][ j ]['score'] = score_diag
dp_matrix[ i ][ j ]['bt'] = 'DIAG'
elif score_del_a >= score_del_b:
dp_matrix[ i ][ j ]['score'] = score_del_a
dp_matrix[ i ][ j ]['bt'] = 'DEL_A'
else:
dp_matrix[ i ][ j ]['score'] = score_del_b
dp_matrix[ i ][ j ]['bt'] = 'DEL_B'
#logger.debug("DP_matrix:\n" + DP_matrix.toString(dp_matrix))
"""
# get max score
max_score = 0
max_i = -1
max_j = -1
for i in range(0,width_a+1):
score = dp_matrix[ i ][ width_b ]['score']
if score > max_score:
max_score = score
max_i = i
max_j = width_b
for j in range(0, width_b+1):
score = dp_matrix[ width_a ][ j ]['score']
if score > max_score:
max_score = score
max_i = width_a
max_j = j
logger.info("found max score {} at position: ({},{})".format(max_score, max_i, max_j))
"""
# keep as global alignment
max_i = width_a
max_j = width_b
# backtrack
i = max_i
j = max_j
all_merged_alignment_nodes_list = list()
while i > 0 or j > 0:
score_struct = dp_matrix[ i ][ j ]
nodes_align_a = align_a.get_node_LIST_at_column_pos(i-1) # again, remember align has zero-based coords, whereas dp_matrix is 1-based
nodes_align_b = align_b.get_node_LIST_at_column_pos(j-1)
align_nodes = list()
bt_dir = score_struct['bt']
#logger.debug("backtrack-dir: " + bt_dir)
if bt_dir == 'DIAG':
i -= 1
j -= 1
align_nodes = nodes_align_a + nodes_align_b
elif bt_dir == 'DEL_B': # UP
i -= 1
align_nodes += nodes_align_a
for x in range(0,len(nodes_align_b)):
align_nodes.append(None)
elif bt_dir == 'DEL_A': # LEFT
j -= 1
for x in range(0,len(nodes_align_a)):
align_nodes.append(None)
align_nodes += nodes_align_b
else:
raise RuntimeError("bt: ({},{}), bt_dir not defined".format(i,j))
all_merged_alignment_nodes_list.append(align_nodes)
all_merged_alignment_nodes_list.reverse()
logger.debug("Merged alignment nodes list: " + str(all_merged_alignment_nodes_list) )
# prep merged alignment obj
merged_transcript_name_list = align_a.get_transcript_names() + align_b.get_transcript_names()
node_obj_matrix = list()
# interate through each node list, reorganize into a matrix
for i in range(0,len(merged_transcript_name_list)):
row = list()
for node_obj_list in all_merged_alignment_nodes_list:
row.append(node_obj_list[i])
node_obj_matrix.append(row)
logger.debug("merged alignment node matrix:\n" + str(node_obj_matrix))
merged_alignment_obj = Node_alignment.Node_alignment(align_a.get_gene_id(), merged_transcript_name_list, node_obj_matrix)
logger.debug("merged alignment obj:\n" + str(merged_alignment_obj))
#sys.exit(1) # DEBUG
return merged_alignment_obj
@staticmethod
def get_match_score(align_a, idx_a, align_b, idx_b):
"""
just determines if indices in two transcripts have the same node identifier
"""
node_set_a = align_a.get_node_set_at_column_pos(idx_a)
node_set_b = align_b.get_node_set_at_column_pos(idx_b)
node_set_a = Node_alignment.Node_alignment.get_node_loc_ids(node_set_a)
node_set_b = Node_alignment.Node_alignment.get_node_loc_ids(node_set_b)
if (set.intersection(node_set_a, node_set_b)):
return 1 # match
else:
return 0 # no match
@staticmethod
def write_malign(gene_name, malign_dict, ofh, align_width=100):
"""
writes the multiply aligned isoform sequences to an output filehandle
"""
transcript_names = list(malign_dict.keys())
alignment_length = len(malign_dict[ transcript_names[ 0 ] ])
align_start = 0
align_text = ""
while align_start < alignment_length:
for transcript_name in transcript_names:
align_region = malign_dict[ transcript_name ][ align_start : min(alignment_length, align_start + align_width) ]
align_text += transcript_name + "\t" + align_region + "\n"
align_text += "\n" # spacer between alignment blocks
align_start += align_width
ofh.write("// {}\n\n{}\n".format(gene_name, align_text))
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