from .usefull_little_functions import * from .intersect import Features,Segments,search_segment,invert_seg from .detect_inversion import detect_feature_inversion,invert_segment_list # functions to get the detail of the variations in the features # handle the variations analysis between the feature on the source genome and the feature on the target genome def generate_variations_details(feature_id,seg_seq,match,file_out_var,segments_on_target_genome): # for each feature, get list of the segments where it is and the first and last segment of the feature on the new genome [first_seg,last_seg,walk,copy_id,feature_target_path]=get_featurePath_ends(match) # do it for the gene, then for its childs. if match[4]==True: # gene passed the filters print_variations(feature_id,first_seg,last_seg,copy_id,walk,seg_seq,feature_target_path,file_out_var,segments_on_target_genome) inversion=detect_feature_inversion(Features[feature_id].segments_list_source,feature_target_path) # print child feature var childs_list=Features[feature_id].get_child_list(Features) for child_id in childs_list: child=Features[child_id] # look for the first and last seg of the child in its parent path [child_first_seg,child_last_seg]=['',''] for seg in child.segments_list_source: # get first seg in the parent path if seg in feature_target_path: # parent path child_first_seg=seg break elif invert_seg(seg) in feature_target_path: child_first_seg=invert_seg(seg) break if child_first_seg!='': # check that the child feature is not absent in this occurence of the parent feature for seg in reversed(child.segments_list_source): # get last seg in the parent path if seg in feature_target_path: # parent path child_last_seg=seg break elif invert_seg(seg) in feature_target_path: child_last_seg=invert_seg(seg) break if inversion: temp=child_first_seg child_first_seg=child_last_seg child_last_seg=temp for match in child.segments_list_target: # look for the right occurence of the child feature if (match[0]==walk) and (match[1]==copy_id): child_target_path=match[2] break # treat the child feature: print_variations(child_id,child_first_seg,child_last_seg,copy_id,walk,seg_seq,child_target_path,file_out_var,segments_on_target_genome) def print_variations(feature_id,first_seg,last_seg,copy_id,walk,seg_seq,feature_target_path,file_out_var,segments_on_target_genome): if first_seg!='': # if the feature is not completly absent # add the else, output absent features [variation,feature_path_source_genome,feature_path_target_genome]=create_var(feature_id,first_seg,last_seg,walk,copy_id,feature_target_path,segments_on_target_genome) # removes the strands in the segment lists feature=Features[feature_id] feat_start=feature.start # loop to go through both paths with i and j [i,j,var_count]=[0,0,0] # detect and print variations ignoring the strands start_feat_seg_target=feature_path_target_genome[0] while (i<len(feature_path_source_genome)) and (j<len(feature_path_target_genome)): if feature_path_source_genome[i] != feature_path_target_genome[j]: # if there is a difference between the two paths if feature_path_target_genome[j] not in feature_path_source_genome: # if the segment in target genome is absent in source genome if feature_path_source_genome[i] not in feature_path_target_genome: # if the segment in source genome is absent is target genome # if both segments are absent in the other genome, its a substitution variation.last_seg_in_target=feature_path_target_genome[j] if (variation.type=='insertion') or (variation.type=='deletion'): # print the current variation before treating the substitution line=print_current_var(variation,feat_start,start_feat_seg_target,feature_id,walk,copy_id,segments_on_target_genome) file_out_var.write(line) reset_var(variation) var_count+=1 if variation.type=='substitution': continue_var(variation,seg_seq,feature_path_source_genome,feature_path_target_genome,i,j,0) else: # initiate substitution init_new_var(variation,"substitution",feature_path_source_genome,feature_path_target_genome,i,j,seg_seq,feature) i+=1;j+=1 else: # target genome segment not in source_genome, but source_genome segment in target genome : insertion or continue substitution if variation.type=='deletion': # print the current variation before treating the insertion line=print_current_var(variation,feat_start,start_feat_seg_target,feature_id,walk,copy_id,segments_on_target_genome) file_out_var.write(line) reset_var(variation) var_count+=1 variation.last_seg_in_target=feature_path_target_genome[j] if variation.type=='insertion': continue_var(variation,seg_seq,feature_path_source_genome,feature_path_target_genome,i,j,0) elif variation.type=="substitution": while feature_path_target_genome[j]!=feature_path_source_genome[i]: continue_var(variation,seg_seq,feature_path_source_genome,feature_path_target_genome,i,j,2) j+=1 line=print_current_var(variation,feat_start,start_feat_seg_target,feature_id,walk,copy_id,segments_on_target_genome) file_out_var.write(line) reset_var(variation) var_count+=1 j-=1 else: # intiate insertion init_new_var(variation,"insertion",feature_path_source_genome,feature_path_target_genome,i,j,seg_seq,feature) j+=1 elif feature_path_source_genome[i] not in feature_path_target_genome: # source_genome segment not in target genome, but target genome segment in source_genome : deletion or continue substitution if variation.type=='insertion': # print the current variation before treating the deletion line=print_current_var(variation,feat_start,start_feat_seg_target,feature_id,walk,copy_id,segments_on_target_genome) file_out_var.write(line) reset_var(variation) var_count+=1 if variation.type=='deletion': continue_var(variation,seg_seq,feature_path_source_genome,feature_path_target_genome,i,j,0) elif variation.type=="substitution": while feature_path_target_genome[j]!=feature_path_source_genome[i]: continue_var(variation,seg_seq,feature_path_source_genome,feature_path_target_genome,i,j,1) i+=1 line=print_current_var(variation,feat_start,start_feat_seg_target,feature_id,walk,copy_id,segments_on_target_genome) file_out_var.write(line) reset_var(variation) var_count+=1 i-=1 else: # intiate deletion init_new_var(variation,"deletion",feature_path_source_genome,feature_path_target_genome,i,j,seg_seq,feature) i+=1 else : # if both segments are present in the other genome but not at the same position. weird case never found yet # can be a substitution. check later if its not an inversion variation.last_seg_in_target=feature_path_target_genome[j] if (variation.type=='insertion') or (variation.type=='deletion'): # print the current variation before treating the substitution line=print_current_var(variation,feat_start,start_feat_seg_target,feature_id,walk,copy_id,segments_on_target_genome) file_out_var.write(line) reset_var(variation) var_count+=1 if variation.type=='substitution': continue_var(variation,seg_seq,feature_path_source_genome,feature_path_target_genome,i,j,0) else: # initiate substitution init_new_var(variation,"substitution",feature_path_source_genome,feature_path_target_genome,i,j,seg_seq,feature) i+=1;j+=1 else: # segment present in both, no variation. print the running indel if there is one if variation.type!='': # print the current variation if there is one line=print_current_var(variation,feat_start,start_feat_seg_target,feature_id,walk,copy_id,segments_on_target_genome) file_out_var.write(line) var_count+=1 reset_var(variation) variation.last_seg_in_target=feature_path_target_genome[j] i+=1;j+=1 if (variation.type!=''): # if there was a current variation when we reached the end, print it line=print_current_var(variation,feat_start,start_feat_seg_target,feature_id,walk,copy_id,file_out_var,segments_on_target_genome) file_out_var.write(line) var_count+=1 reset_var(variation) if i<=len(feature_path_source_genome)-1: # if we didn't reach the length of the segment list for the first genome, the end is missing for the second genome line=print_last_deletion(variation,feature_path_source_genome,i,feat_start,feature,seg_seq) file_out_var.write(line) var_count+=1 reset_var(variation) if var_count==0: # if no variation was encountered line=print_novar(variation) file_out_var.write(line) # print a variation def print_current_var(variation,feat_start,start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome): warning='' if variation.type=='insertion': [pos_old,pos_new]=get_old_new_pos_insertion(variation,feat_start,start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome) line=f'{variation.feature_id}\t{variation.feature_type}\t{variation.chr}\t{variation.start_new}\t{variation.stop_new}\t{variation.size_new}\t{print_inversion(variation.inversion)}\t{variation.size_diff}\tinsertion\t-\t{variation.alt}\t{len(variation.alt)}\t{pos_old}\t{pos_new}{warning}\n' return line elif variation.type=='deletion': [pos_old,pos_new]=get_old_new_pos_deletion(variation,feat_start,start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome) line=f'{variation.feature_id}\t{variation.feature_type}\t{variation.chr}\t{variation.start_new}\t{variation.stop_new}\t{variation.size_new}\t{print_inversion(variation.inversion)}\t{variation.size_diff}\tdeletion\t{variation.ref}\t-\t{len(variation.ref)}\t{pos_old}\t{pos_new}{warning}\n' return line elif variation.type=='substitution': warning=detect_small_inversion(variation) [pos_old,pos_new]=get_old_new_pos_substitution(feat_start,variation,start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome) size_subs=f'{len(variation.ref)}/{len(variation.alt)}' line=f'{variation.feature_id}\t{variation.feature_type}\t{variation.chr}\t{variation.start_new}\t{variation.stop_new}\t{variation.size_new}\t{print_inversion(variation.inversion)}\t{variation.size_diff}\tsubstitution\t{variation.ref}\t{variation.alt}\t{size_subs}\t{pos_old}\t{pos_new}{warning}\n' # print the substitutions of different size as deletion+insertion. #if len(variation.ref) == len(variation.alt): # if the substituion is between two segment of the same size, print it # size_subs=len(variation.ref) # line=f'{variation.feature_id}\t{variation.feature_type}\t{variation.chr}\t{variation.start_new}\t{variation.stop_new}\t{variation.size_new}\t{inversion}\t{variation.size_diff}\tsubstitution\t{variation.ref}\t{variation.alt}\t{size_subs}\t{pos_old}\t{pos_new}{warning}\n' #else : # # if the segments of the substitution have a different size, print deletion then insertion at the same position. # line=f'{variation.feature_id}\t{variation.feature_type}\t{variation.chr}\t{variation.start_new}\t{variation.stop_new}\t{variation.size_new}\t{inversion}\t{variation.size_diff}\tdeletion\t{variation.ref}\t-\t{len(variation.ref)}\t{pos_old}\t{pos_new}{warning}\n' # line+=f'{variation.feature_id}\t{variation.feature_type}\t{variation.chr}\t{variation.start_new}\t{variation.stop_new}\t{variation.size_new}\t{inversion}\t{variation.size_diff}\tinsertion\t-\t{variation.alt}\t{len(variation.alt)}\t{pos_old}\t{pos_new}{warning}\n' return line # check if a substitution could be an inversion inside a feature def detect_small_inversion(variation): [list_ref_common,list_alt_common]=[list(),list()] list_ref_unstrand=[segment_stranded[1:] for segment_stranded in variation.seg_ref] list_alt_unstrand=[segment_stranded[1:] for segment_stranded in variation.seg_alt] for seg in variation.seg_ref: if seg[1:] in list_alt_unstrand: list_ref_common.append(seg) for seg in variation.seg_alt: if seg[1:] in list_ref_unstrand: list_alt_common.append(seg) if (len(list_ref_common)>len(list_ref_unstrand)*0.5) and (len(list_alt_common)>len(list_alt_unstrand)*0.5): return f'\t# Suspected inversion within this substitution.' else: return '' # print a deletion at the end of a feature def print_last_deletion(variation,feature_path_source_genome,i,feat_start,feature,seg_seq): seg_del=search_segment(feature_path_source_genome[i]) pos_old=int(Segments[seg_del].get_start(feature.id))-int(feat_start)+1 del_sequence=get_sequence_list_seg(feature_path_source_genome,i,feature,seg_seq) length=len(del_sequence) pos_new=str(int(variation.size_new)+1) # the deletion is at the end of the feature on the new genome if variation.inversion: inversion='1' else: inversion='0' line=f'{variation.feature_id}\t{variation.feature_type}\t{variation.chr}\t{variation.start_new}\t{variation.stop_new}\t{variation.size_new}\t{inversion}\t{variation.size_diff}\tdeletion\t{del_sequence}\t-\t{length}\t{pos_old}\t{pos_new}\n' return line # print a feature with no variation def print_novar(variation): line=f'{variation.feature_id}\t{variation.feature_type}\t{variation.chr}\t{variation.start_new}\t{variation.stop_new}\t{variation.size_new}\t{print_inversion(variation.inversion)}\t{variation.size_diff}\tno_var\t-\t-\t-\t-\t-\n' return line # get a digit for the inversion (convert bool in int) def print_inversion(bool): if bool==True: return '1' else: return '0' # initiate a Variation object with the information on the feature it is on def create_var(feature_id,first_seg,last_seg,walk,copy_id,feature_target_path,segments_on_target_genome): feature=Features[feature_id] # get feature paths on the original genome and on the target genome feature_path_target_genome=feature_target_path feature_path_source_genome=feature.segments_list_source inversion=detect_feature_inversion(feature_path_source_genome,feature_path_target_genome) if inversion: feature_path_target_genome=invert_segment_list(feature_path_target_genome) stop_new_genome=get_feature_start_on_target_genome_inv(last_seg,feature_id,walk,copy_id,segments_on_target_genome) start_new_genome=get_feature_stop_on_target_genome_inv(first_seg,feature_id,walk,copy_id,segments_on_target_genome) else: start_new_genome=get_feature_start_on_target_genome(first_seg,feature_id,walk,copy_id,segments_on_target_genome) stop_new_genome=get_feature_stop_on_target_genome(last_seg,feature_id,walk,copy_id,segments_on_target_genome) size_new_genome=stop_new_genome-start_new_genome+1 size_diff=str(size_new_genome-feature.size) sequence_name=get_seg_occ(first_seg,walk,feature_id,copy_id,segments_on_target_genome)[0] variation=Variation(feature.id,feature_id,feature.type,sequence_name,start_new_genome,stop_new_genome,inversion,size_diff,size_new_genome) return(variation,feature_path_source_genome,feature_path_target_genome) # reset the informations of the variation, but keep the information about the feature def reset_var(variation): variation.type='' # make type enumerate variation.size_var=0 variation.start_var='' variation.start_var_index=0 variation.ref='' variation.alt='' # find the position of a substitution on the source and the target sequence def get_old_new_pos_substitution(feat_start,variation,start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome): seg_pos=search_segment(variation.start_var) pos_old=str(int(Segments[seg_pos].get_start(Features[feat].id))-int(feat_start)) var_start_seg=variation.start_on_target if variation.inversion: start_feat_seg_target=invert_seg(start_feat_seg_target) var_start_seg=invert_seg(var_start_seg) end_var=get_seg_occ(var_start_seg,walk,feat,copy_id,segments_on_target_genome)[2] start_feat=get_feature_start_on_target_genome_inv(start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome) pos_new=str(start_feat-end_var) else: start_var=get_seg_occ(var_start_seg,walk,feat,copy_id,segments_on_target_genome)[1] start_feat=get_feature_start_on_target_genome(start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome) pos_new=str(start_var-start_feat) return [pos_old,pos_new] # pos_old and pos_new are the base before the change # find the position of an insertion on the source and the target sequence def get_old_new_pos_insertion(variation,feat_start,start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome): seg_pos=search_segment(variation.start_var) # start_var is the segment AFTER the insertion pos_old=str(int(Segments[seg_pos].get_start(Features[feat].id))-int(feat_start)) start_var_seg=variation.start_var if variation.inversion: start_feat_seg_target=invert_seg(start_feat_seg_target) start_var_seg=invert_seg(start_var_seg) end_var=get_seg_occ(start_var_seg,walk,feat,copy_id,segments_on_target_genome)[2]+len(variation.alt) # start_var_seg is the segment AFTER the insertion start_feat=get_feature_start_on_target_genome_inv(start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome) pos_new=str(start_feat-end_var) else: start_var=get_seg_occ(start_var_seg,walk,feat,copy_id,segments_on_target_genome)[1]-len(variation.alt) # start_var_seg is the segment AFTER the insertion start_feat=get_feature_start_on_target_genome(start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome) pos_new=str(start_var-start_feat) return [pos_old,pos_new] # pos_old and pos_new are the base before the change # find the position of a deletion on the source and the target sequence def get_old_new_pos_deletion(variation,feat_start,start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome): i=variation.start_var_index seg_pos=search_segment(variation.start_var) if i==0: pos_old=int(Segments[seg_pos].get_start(Features[feat].id))-int(feat_start)+Features[feat].pos_start-1 else: pos_old=int(Segments[seg_pos].get_start(Features[feat].id))-int(feat_start) if pos_old<0: pos_old=0 print("error with variation position",variation.inversion,"***") if variation.last_seg_in_target=="": # deletion of the beggining of the feature, so no segment placed in the new genome yet. pos_new=0 else: start_var_seg=variation.last_seg_in_target if variation.inversion: start_feat_seg_target=invert_seg(start_feat_seg_target) start_var_seg=invert_seg(start_var_seg) start_var=get_seg_occ(start_var_seg,walk,feat,copy_id,segments_on_target_genome)[1]-1 start_feat=get_feature_start_on_target_genome_inv(start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome) pos_new=str(start_feat-start_var) else: start_var=get_seg_occ(start_var_seg,walk,feat,copy_id,segments_on_target_genome)[2]+1 start_feat=get_feature_start_on_target_genome(start_feat_seg_target,feat,walk,copy_id,segments_on_target_genome) pos_new=str(start_var-start_feat) return [pos_old,pos_new] # pos_old and pos_new are the base before the change # change the variation information, but keep the feature information (the variation is on the feature) def init_new_var(variation,type,feature_path_source_genome,feature_path_target_genome,i,j,seg_seq,feature): variation.type=type variation.start_var=feature_path_source_genome[i] variation.start_var_index=i if type=="substitution": variation.start_on_target=feature_path_target_genome[j] variation.ref=get_segment_sequence(seg_seq,feature_path_source_genome[i]) variation.alt=get_segment_sequence(seg_seq,feature_path_target_genome[j]) variation.seg_ref.append(feature_path_source_genome[i]) variation.seg_alt.append(feature_path_target_genome[j]) elif type=="insertion": variation.ref="-" variation.alt=get_segment_sequence(seg_seq,feature_path_target_genome[j]) variation.seg_alt.append(feature_path_target_genome[j]) elif type=="deletion": if i==0: # if the deletion is at the start of the feature, the deletion doesnt always start at the start at the first segment : #use pos_start, position of the feature on its first segment variation.ref=get_segment_sequence(seg_seq,feature_path_source_genome[i])[feature.pos_start-1:] variation.seg_ref.append(feature_path_source_genome[i]) else: # else, the deletion will always start at the start of the first segment. variation.ref=get_segment_sequence(seg_seq,feature_path_source_genome[i]) variation.seg_ref.append(feature_path_source_genome[i]) variation.alt="-" # update the variation def continue_var(variation,seg_seq,feature_path_source_genome,feature_path_target_genome,i,j,genome_to_continue): if variation.type=="substitution": if genome_to_continue==0: # genome_to_continue allows to choose if the substitution continues for the original or the target genome, or both. variation.ref+=get_segment_sequence(seg_seq,feature_path_source_genome[i]) variation.alt+=get_segment_sequence(seg_seq,feature_path_target_genome[j]) variation.seg_ref.append(feature_path_source_genome[i]) variation.seg_alt.append(feature_path_target_genome[j]) elif genome_to_continue==1: # deletion variation.ref+=get_segment_sequence(seg_seq,feature_path_source_genome[i]) variation.seg_ref.append(feature_path_source_genome[i]) elif genome_to_continue==2: # insertion variation.alt+=get_segment_sequence(seg_seq,feature_path_target_genome[j]) variation.seg_alt.append(feature_path_target_genome[j]) elif variation.type=="insertion": variation.alt+=get_segment_sequence(seg_seq,feature_path_target_genome[j]) variation.seg_alt.append(feature_path_target_genome[j]) elif variation.type=="deletion": variation.ref+=get_segment_sequence(seg_seq,feature_path_source_genome[i]) variation.seg_ref.append(feature_path_source_genome[i]) # stores information about a feature and its current variation class Variation: def __init__(self,feature_id,feature_key,feature_type,chr,start_new,stop_new,inversion,size_diff,size_new): self.feature_id=feature_id # real id in the gff self.feature_key=feature_key # key to access the feature info in the dict Features self.feature_type=feature_type self.chr=chr self.start_new=start_new self.stop_new=stop_new self.inversion=inversion self.size_diff=size_diff self.size_new=size_new self.type='' self.last_seg_in_target='' self.seg_ref=list() self.seg_alt=list() # outputs the nucleotide sequence of a list of segments, corresponding to the end of a feature def get_sequence_list_seg(list_seg,i,feature,seg_seq): del_sequence="" for k in range(i,len(list_seg)): if k==len(list_seg)-1: del_sequence+=get_segment_sequence(seg_seq,list_seg[k])[0:feature.pos_stop] else: del_sequence+=get_segment_sequence(seg_seq,list_seg[k]) return del_sequence