2 # = lib/evo/io/parser/hmmscan_domain_extractor.rb - HmmscanMultiDomainExtractor class
4 # Copyright:: Copyright (C) 2017 Christian M. Zmasek
5 # License:: GNU Lesser General Public License (LGPL)
7 # Last modified: 2017/02/20
9 require 'lib/evo/util/constants'
10 require 'lib/evo/msa/msa_factory'
11 require 'lib/evo/io/msa_io'
12 require 'lib/evo/io/writer/fasta_writer'
13 require 'lib/evo/io/parser/fasta_parser'
14 require 'lib/evo/io/parser/hmmscan_parser'
17 class HmmscanMultiDomainExtractor
21 DOMAIN_DELIMITER = ' -- '
23 IE_CUTOFF_FOR_DA_OVERVIEW = 1E-6
24 REL_LEN_CUTOFF_FOR_DA_OVERVIEW = 0.5
26 PASSING_FL_SEQS_SUFFIX = "_#{OUTPUT_ID}_passing_full_length_seqs.fasta"
27 FAILING_FL_SEQS_SUFFIX = "_#{OUTPUT_ID}_failing_full_length_seqs.fasta"
28 TARGET_DA_SUFFIX = "_#{OUTPUT_ID}_target_da.fasta"
29 CONCAT_TARGET_DOM_SUFFIX = "_#{OUTPUT_ID}_concat_target_doms.fasta"
30 TARGET_DOM_OUTPUT_MIDPART = "_#{OUTPUT_ID}_target_dom_"
31 LOG_FILE_SUFFIX = "_#{OUTPUT_ID}.log"
33 @passing_domains_data = nil
34 @failing_domains_data = nil
35 @failing_domain_architectures = nil
36 @passsing_domain_architectures = nil
37 @failing_proteins_bc_not_all_target_doms_present = nil
38 @failing_proteins_bc_missing_cutoffs = nil
39 @encountered_domain_architectures = nil
43 # raises ArgumentError, IOError, StandardError
50 passing_fl_seqs_outfile = outfile_base + PASSING_FL_SEQS_SUFFIX
51 failing_fl_seqs_outfile = outfile_base + FAILING_FL_SEQS_SUFFIX
52 target_da_outfile = outfile_base + TARGET_DA_SUFFIX
53 concat_target_dom_outfile = outfile_base + CONCAT_TARGET_DOM_SUFFIX
54 logfile = outfile_base + LOG_FILE_SUFFIX
56 Util.check_file_for_readability( hmmscan_output )
57 Util.check_file_for_readability( fasta_sequence_file )
58 Util.check_file_for_writability( passing_fl_seqs_outfile )
59 Util.check_file_for_writability( failing_fl_seqs_outfile )
60 Util.check_file_for_writability( target_da_outfile )
61 Util.check_file_for_writability( concat_target_dom_outfile )
62 Util.check_file_for_writability( logfile )
67 factory = MsaFactory.new()
68 in_msa = factory.create_msa_from_file( fasta_sequence_file, FastaParser.new() )
70 if ( in_msa == nil || in_msa.get_number_of_seqs() < 1 )
71 error_msg = "could not find fasta sequences in " + fasta_sequence_file
72 raise IOError, error_msg
75 failed_seqs_msa = Msa.new
76 passed_seqs_msa = Msa.new
78 hmmscan_parser = HmmscanParser.new( hmmscan_output )
79 results = hmmscan_parser.parse
82 # Import: if multiple copies of same domain, thresholds need to be same!
84 #target_domain_ary.push(TargetDomain.new('DNA_pol_B_exo1', 1e-6, -1, 0.6, 0 ))
85 #target_domain_ary.push(TargetDomain.new('DNA_pol_B', 1e-6, -1, 0.6, 1 ))
87 #target_domain_ary.push(TargetDomain.new('Hexokinase_1', 1e-6, -1, 0.9, 0 ))
88 #target_domain_ary.push(TargetDomain.new('Hexokinase_2', 1e-6, -1, 0.9, 1 ))
89 # target_domain_ary.push(TargetDomain.new('Hexokinase_2', 0.1, -1, 0.5, 1 ))
90 # target_domain_ary.push(TargetDomain.new('Hexokinase_1', 0.1, -1, 0.5, 1 ))
92 target_domain_ary = parse_da target_da
94 # target_domain_ary.push(TargetDomain.new('BH4', 1, -1, 0.2, 0 ))
95 # target_domain_ary.push(TargetDomain.new('Bcl-2', 1, -1, 0.2, 1 ))
96 # target_domain_ary.push(TargetDomain.new('Bcl-2', 1, -1, 0.2, 2 ))
97 # target_domain_ary.push(TargetDomain.new('Bcl-2_3', 0.01, -1, 0.5, 2 ))
99 # target_domain_ary.push(TargetDomain.new('Nitrate_red_del', 1000, -1, 0.1, 0 ))
100 # target_domain_ary.push(TargetDomain.new('Nitrate_red_del', 1000, -1, 0.1, 1 ))
102 #target_domain_ary.push(TargetDomain.new('Chordopox_A33R', 1000, -1, 0.1 ))
104 target_domains = Hash.new
106 target_domain_architecure = ''
108 target_domain_ary.each do |target_domain|
109 target_domains[target_domain.name] = target_domain
110 if target_domain_architecure.length > 0
111 target_domain_architecure << DOMAIN_DELIMITER
113 target_domain_architecure << target_domain.name
116 target_domain_architecure.freeze
118 log 'Hmmscan outputfile : ' + hmmscan_output
119 log 'Full length fasta sequence file: ' + fasta_sequence_file
120 log 'Target domain architecture : ' + target_domain_architecure
121 target_domain_ary.each do |x|
125 target_domain_names = Set.new
127 target_domains.each_key {|key| target_domain_names.add( key ) }
129 prev_query_seq_name = nil
130 domains_in_query_seq = Array.new
131 passing_sequences = Array.new # This will be an Array of Array of HmmscanResult for the same query seq.
132 failing_sequences = Array.new # This will be an Array of Array of HmmscanResult for the same query seq.
135 @failing_domain_architectures = Hash.new
136 @passsing_domain_architectures = Hash.new
137 @passing_domains_data = Hash.new
138 @failing_domains_data = Hash.new
139 @encountered_domain_architectures= Hash.new
140 @failing_proteins_bc_not_all_target_doms_present = 0
141 @failing_proteins_bc_missing_cutoffs = 0
142 out_domain_msas = Hash.new
143 out_domain_architecture_msa = Msa.new
144 out_concatenated_domains_msa = Msa.new
145 results.each do |hmmscan_result|
146 if ( prev_query_seq_name != nil ) && ( hmmscan_result.query != prev_query_seq_name )
147 if compare(domains_in_query_seq, target_domain_names, target_domains, in_msa, out_domain_msas, out_domain_architecture_msa, out_concatenated_domains_msa, target_domain_architecure)
148 passing_sequences.push(domains_in_query_seq)
150 failing_sequences.push(domains_in_query_seq)
152 domains_in_query_seq = Array.new
155 prev_query_seq_name = hmmscan_result.query
156 domains_in_query_seq.push(hmmscan_result)
159 if prev_query_seq_name != nil
160 if compare(domains_in_query_seq, target_domain_names, target_domains, in_msa, out_domain_msas, out_domain_architecture_msa, out_concatenated_domains_msa, target_domain_architecure)
161 passing_sequences.push(domains_in_query_seq)
163 failing_sequences.push(domains_in_query_seq)
168 if in_msa.get_number_of_seqs < total_sequences
169 error_msg = "hmmscan output contains more protein sequences than fasta sequence file"
170 raise IOError, error_msg
174 log 'Domain architecture overview using default iE-cutoff ' +
175 IE_CUTOFF_FOR_DA_OVERVIEW.to_s + ' and relative length cutoff ' + REL_LEN_CUTOFF_FOR_DA_OVERVIEW.to_s + ':'
177 @encountered_domain_architectures = @encountered_domain_architectures.sort_by {|k, v| v}.reverse.to_h
179 @encountered_domain_architectures.each do |k, v|
180 log counter.to_s.rjust(2) + ') ' + v.to_s.rjust(5) + ': ' + k
188 log 'Passing domain architectures containing target domain(s):'
189 @passsing_domain_architectures = @passsing_domain_architectures.sort{|a, b|a<=>b}.to_h
191 @passsing_domain_architectures.each do |da, count|
192 passing_da_sum += count
193 log count.to_s.rjust(4) + ': ' + da
196 log 'Failing domain architectures containing one or more target domain(s):'
197 @failing_domain_architectures = @failing_domain_architectures .sort{|a, b|a<=>b}.to_h
199 @failing_domain_architectures .each do |da, count|
200 failing_da_sum += count
201 log count.to_s.rjust(4) + ': ' + da
204 log 'Passing target domain(s):'
205 @passing_domains_data = @passing_domains_data.sort{|a, b|a<=>b}.to_h
206 @passing_domains_data.each do |n, d|
210 log'Failing target domain(s):'
211 @failing_domains_data = @failing_domains_data.sort{|a, b|a<=>b}.to_h
212 @failing_domains_data.each do |n, d|
216 unless total_sequences == (passing_sequences.size + failing_sequences.size)
217 error_msg = "this should not have happened: total seqs not equal to passing plus failing seqs"
218 raise StandardError, error_msg
221 unless failing_sequences.size == (@failing_proteins_bc_not_all_target_doms_present + @failing_proteins_bc_missing_cutoffs)
222 error_msg = "this should not have happened: failing seqs sums not consistent"
223 raise StandardError, error_msg
226 unless @failing_proteins_bc_missing_cutoffs == failing_da_sum
227 error_msg = "this should not have happened: failing seqs not equal to failing da sum"
228 raise StandardError, error_msg
231 unless passing_sequences.size == passing_da_sum
232 error_msg = "this should not have happened: passing seqs not equal to passing da sum"
233 raise StandardError, error_msg
237 log "Protein sequences in sequence (fasta) file: " + in_msa.get_number_of_seqs.to_s.rjust(5)
238 log "Protein sequences in hmmscan output file : " + total_sequences.to_s.rjust(5)
239 log " Passing protein sequences : " + passing_sequences.size.to_s.rjust(5)
240 log " Failing protein sequences : " + failing_sequences.size.to_s.rjust(5)
241 log " Not all target domain present : " + @failing_proteins_bc_not_all_target_doms_present.to_s.rjust(5)
242 log " Target domain(s) failing cutoffs : " + @failing_proteins_bc_missing_cutoffs.to_s.rjust(5)
245 out_domain_msas.keys.sort.each do |domain_name|
246 file_name = outfile_base + TARGET_DOM_OUTPUT_MIDPART + domain_name + '.fasta'
247 write_msa out_domain_msas[domain_name], file_name
248 log "Wrote passing target domain sequence for " + domain_name.ljust(16) + ': ' + file_name
251 write_msa out_domain_architecture_msa, target_da_outfile
252 log 'Wrote target domain architecture : ' + target_da_outfile
254 write_msa out_concatenated_domains_msa, concat_target_dom_outfile
255 log 'Wrote concatenated target domain(s) : ' + concat_target_dom_outfile
257 passing_sequences.each do | domains |
258 query_name = domains[0].query
259 if (!TESTING) || (passed_seqs_msa.find_by_name_start( query_name, true ).length < 1)
260 add_sequence( query_name, in_msa, passed_seqs_msa )
262 error_msg = 'this should not have happened'
263 raise StandardError, error_msg
267 failing_sequences.each do | domains |
268 query_name = domains[0].query
269 if (!TESTING) || (failed_seqs_msa.find_by_name_start( query_name, true ).length < 1)
270 add_sequence( query_name, in_msa, failed_seqs_msa )
272 error_msg = 'this should not have happened'
273 raise StandardError, error_msg
277 write_msa passed_seqs_msa, passing_fl_seqs_outfile
278 log 'Wrote passing full length protein sequences : ' + passing_fl_seqs_outfile
279 write_msa failed_seqs_msa, failing_fl_seqs_outfile
280 log 'Wrote failing full length protein sequences : ' + failing_fl_seqs_outfile
283 f = File.open( logfile, 'w' )
286 rescue Exception => e
287 Util.fatal_error( PRG_NAME, "error: " + e.to_s )
289 log 'Wrote log file : ' + logfile
295 # domains: Array of HmmscanResult
296 def collect(domains, ie_cutoff, rel_len_cutoff)
298 domains.each do |domain|
299 length = 1 + domain.env_to - domain.env_from
300 if (domain.i_e_value <= ie_cutoff) && (length >= (rel_len_cutoff * domain.tlen))
304 passed.sort! { |a,b| a.ali_from <=> b.ali_from }
306 passed.each do |domain|
308 s << DOMAIN_DELIMITER
313 if @encountered_domain_architectures.has_key? s
314 @encountered_domain_architectures[s] = 1 + @encountered_domain_architectures[s]
316 @encountered_domain_architectures[s] = 1
321 # domains_in_query_seq: Array of HmmscanResult
322 # target_domain_names: Set of String
323 # target_domains: Hash String->TargetDomain
324 # target_domain_architecture: String
325 def compare(domains_in_query_seq,
330 out_domain_architecture_msa,
331 out_contactenated_domains_msa,
332 target_domain_architecture)
334 collect(domains_in_query_seq, IE_CUTOFF_FOR_DA_OVERVIEW, REL_LEN_CUTOFF_FOR_DA_OVERVIEW)
336 domain_names_in_query_seq = Set.new
337 domains_in_query_seq.each do |domain|
338 domain_names_in_query_seq.add(domain.model)
340 if target_domain_names.subset?(domain_names_in_query_seq)
342 passed_domains = Array.new
343 passed_domains_counts = Hash.new
345 domains_in_query_seq.each do |domain|
346 if target_domains.has_key?(domain.model)
347 target_domain = target_domains[domain.model]
349 if (target_domain.i_e_value != nil) && (target_domain.i_e_value >= 0)
350 if domain.i_e_value > target_domain.i_e_value
351 addToFailingDomainData(domain)
355 if (target_domain.abs_len != nil) && (target_domain.abs_len > 0)
356 length = 1 + domain.env_to - domain.env_from
357 if length < target_domain.abs_len
358 addToFailingDomainData(domain)
362 if (target_domain.rel_len != nil) && (target_domain.rel_len > 0)
363 length = 1 + domain.env_to - domain.env_from
364 if length < (target_domain.rel_len * domain.tlen)
365 addToFailingDomainData(domain)
370 passed_domains.push(domain)
372 if (passed_domains_counts.key?(domain.model))
373 passed_domains_counts[domain.model] = passed_domains_counts[domain.model] + 1
375 passed_domains_counts[domain.model] = 1
378 addToPassingDomainData(domain)
380 end # if target_domains.has_key?(domain.model)
381 end # domains_in_query_seq.each do |domain|
383 @failing_proteins_bc_not_all_target_doms_present += 1
385 end # target_domain_names.subset?(domain_names_in_query_seq)
387 passed_domains.sort! { |a,b| a.ali_from <=> b.ali_from }
388 # Compare architectures
389 if !compareArchitectures(target_domain_architecture, passed_domains)
390 @failing_proteins_bc_missing_cutoffs += 1
394 domain_counter = Hash.new
396 min_env_from = 10000000
401 concatenated_domains = ''
403 passed_domains.each do |domain|
404 domain_name = domain.model
406 unless out_domain_msas.has_key? domain_name
407 out_domain_msas[ domain_name ] = Msa.new
410 if domain_counter.key?(domain_name)
411 domain_counter[domain_name] = domain_counter[domain_name] + 1
413 domain_counter[domain_name] = 1
417 query_seq = domain.query
419 elsif query_seq != domain.query
420 error_msg = "seq names do not match: this should not have happened"
421 raise StandardError, error_msg
424 extracted_domain_seq = extract_domain( query_seq,
425 domain_counter[domain_name],
426 passed_domains_counts[domain_name],
430 out_domain_msas[ domain_name ] )
432 concatenated_domains += extracted_domain_seq
434 if domain.env_from < min_env_from
435 min_env_from = domain.env_from
437 if domain.env_to > max_env_to
438 max_env_to = domain.env_to
442 extract_domain( query_seq,
448 out_domain_architecture_msa )
450 out_contactenated_domains_msa.add( query_seq, concatenated_domains)
455 def addToPassingDomainData(domain)
456 unless ( @passing_domains_data.key?(domain.model))
457 @passing_domains_data[domain.model] = DomainData.new(domain.model)
459 @passing_domains_data[domain.model].add( domain.model, (1 + domain.env_to - domain.env_from), domain.i_e_value)
462 def addToFailingDomainData(domain)
463 unless ( @failing_domains_data.key?(domain.model))
464 @failing_domains_data[domain.model] = DomainData.new(domain.model)
466 @failing_domains_data[domain.model].add( domain.model, (1 + domain.env_to - domain.env_from), domain.i_e_value)
469 # passed_domains needs to be sorted!
470 def compareArchitectures(target_domain_architecture, passed_domains, strict = false)
471 domain_architecture = ''
472 passed_domains.each do |domain|
473 if domain_architecture.length > 0
474 domain_architecture += DOMAIN_DELIMITER
476 domain_architecture += domain.model
480 pass = (target_domain_architecture == domain_architecture)
482 pass = (domain_architecture.index(target_domain_architecture) != nil)
485 if (@passsing_domain_architectures.key?(domain_architecture))
486 @passsing_domain_architectures[domain_architecture] = @passsing_domain_architectures[domain_architecture] + 1
488 @passsing_domain_architectures[domain_architecture] = 1
491 if ( @failing_domain_architectures .key?(domain_architecture))
492 @failing_domain_architectures [domain_architecture] = @failing_domain_architectures [domain_architecture] + 1
494 @failing_domain_architectures [domain_architecture] = 1
500 def write_msa( msa, filename )
502 w = FastaWriter.new()
503 w.set_line_width( 60 )
505 File.delete(filename) if File.exist?(filename)
507 io.write_to_file( msa, filename, w )
509 error_msg = "could not write to \"" + filename + "\""
510 raise IOError, error_msg
514 def add_sequence( sequence_name, in_msa, add_to_msa )
515 seqs = in_msa.find_by_name_start( sequence_name, true )
516 if ( seqs.length < 1 )
517 error_msg = "sequence \"" + sequence_name + "\" not found in sequence file"
518 raise StandardError, error_msg
520 if ( seqs.length > 1 )
521 error_msg = "sequence \"" + sequence_name + "\" not unique in sequence file"
522 raise StandardError, error_msg
524 seq = in_msa.get_sequence( seqs[ 0 ] )
525 add_to_msa.add_sequence( seq )
528 def extract_domain( seq_name,
535 if number < 1 || out_of < 1 || number > out_of
536 error_msg = "number=" + number.to_s + ", out of=" + out_of.to_s
537 raise StandardError, error_msg
539 if seq_from < 1 || seq_to < 1 || seq_from >= seq_to
540 error_msg = "impossible: seq-from=" + seq_from.to_s + ", seq-to=" + seq_to.to_s
541 raise StandardError, error_msg
543 seqs = in_msa.find_by_name_start(seq_name, true)
545 error_msg = "sequence \"" + seq_name + "\" not found in sequence file"
546 raise IOError, error_msg
549 error_msg = "sequence \"" + seq_name + "\" not unique in sequence file"
550 raise IOError, error_msg
552 # hmmscan is 1 based, whereas sequences are 0 bases in this package.
553 seq = in_msa.get_sequence( seqs[ 0 ] ).get_subsequence( seq_from - 1, seq_to - 1 )
555 orig_name = seq.get_name
557 seq.set_name( orig_name.split[ 0 ] )
560 seq.set_name( seq.get_name + "~" + number.to_s + "-" + out_of.to_s )
563 out_msa.add_sequence( seq )
565 seq.get_sequence_as_string
568 def parse_da( target_da_str )
569 target_domain_hash = Hash.new
570 target_domain_ary = Array.new
571 target_das = target_da_str.split '--'
572 target_das.each do |x|
574 unless inds.size == 4
575 raise IOError, 'domain architecture is ill formatted: ' + x
577 target_domain_name = inds[0]
578 ie_cutoff = Float(inds[1])
579 abs_len_cutoff = Integer(inds[2])
580 rel_len_cutoff = Float(inds[3])
581 if target_domain_hash.has_key? target_domain_name
582 target_domain_ary.push target_domain_hash[target_domain_name]
584 td = TargetDomain.new(target_domain_name, ie_cutoff, abs_len_cutoff, rel_len_cutoff)
585 target_domain_hash[target_domain_name] = td
586 target_domain_ary.push td
594 @log << str << Constants::LINE_DELIMITER
597 end # class HmmscanMultiDomainExtractor
600 def initialize( name )
601 if (name == nil) || name.size < 1
602 error_msg = "domain name nil or empty"
603 raise IOError, error_msg
607 @i_e_value_min = 10000000.0
608 @i_e_value_max = -1.0
615 def add( name, length, i_e_value)
617 error_msg = "domain names do not match"
618 raise IOError, error_msg
622 error_msg = "length cannot me negative"
623 raise IOError, error_msg
626 error_msg = "iE-value cannot me negative"
627 raise IOError, error_msg
630 @i_e_value_sum += i_e_value
632 if i_e_value > @i_e_value_max
633 @i_e_value_max = i_e_value
635 if i_e_value < @i_e_value_min
636 @i_e_value_min = i_e_value
657 @i_e_value_sum / @count
662 s << @name.rjust(16) + ': '
663 s << @count.to_s.rjust(4) + ' '
664 s << avg_length.round(1).to_s.rjust(6) + ' '
665 s << @len_min.to_s.rjust(4) + ' -'
666 s << @len_max.to_s.rjust(4) + ' '
667 s << ("%.2E" % avg_i_e_value).rjust(9) + ' '
668 s << ("%.2E" % @i_e_value_min).rjust(9) + ' -'
669 s << ("%.2E" % @i_e_value_max).rjust(9) + ' '
673 attr_reader :name, :count, :i_e_value_min, :i_e_value_max, :length_min, :length_max
678 def initialize(name, i_e_value, abs_len, rel_len)
679 if (name == nil) || name.size < 1
680 error_msg = "target domain name nil or empty"
681 raise IOError, error_msg
684 error_msg = name + ": target domain relative length is greater than 1"
685 raise IOError, error_msg
687 if (abs_len <= 0) && (rel_len <= 0)
688 error_msg = name + ": need to have either absolute length or relative length cutoff"
689 raise IOError, error_msg
691 if (abs_len > 0) && (rel_len > 0)
692 error_msg = name + ": cannot have both absolute length and relative length cutoff"
693 raise IOError, error_msg
696 @i_e_value = i_e_value
702 s = @name.rjust(16) + ':'
703 s << ' iE-cutoff: ' + ("%.2E" % @i_e_value).rjust(9)
705 s << ', abs len-cutoff: ' + @abs_len.to_s.rjust(4)
708 s << ', rel len-cutoff: ' + @rel_len.to_s.rjust(4)
712 attr_reader :name, :i_e_value, :abs_len, :rel_len