【正文】 PMsearch is a pathway parison program. After a user specifies a query pathway, and a search database, PMsearch will pare the query pathway with each entry in the pathway database. The query pathway is specified by two input files: a pathway file, and a , the protein file. The contains the pathway information, in FASTA format, and the contains the involved proteins, in FASTA format. The pathway database is also posed of two files, a and a file, except the database files contain more than one entry. Once a job is submitted, the search engine (pm_search) will perform the job, and report back all the homologous pathways that are above a userspecified threshold. The user can also specify other parameters, which are given in the user manual. Given a list of letters, UIPQWEFOIUFJLK and PQEFOIABCDFJ, a good alignment might be: UIPQWXEFOIUFJLK || |||| || PQEFOIABCDFJQRS Specifics for pathway alignment: 1. Each letter can represent a node, or a mode. 2. Nodes do not have to be identical in order to match。 they just have to be homologous. 3. Distance between nodes and modes, and between protein nodes and nonprotein nodes are infinite, you cannot align different types of elements. In the simplest case, consider pathway with only protein nodes. Given an alignment z, the score is given by where s(x,y) is the similarity of protein x and protein y, ngap is the number of gaps in z, lgap is the total length of the gaps, Δ is a parameter called the “gap opening” penalty, and δ is a second parameter called the “gap extension” penalty. There are many possible alignment for two pathways, and different alignments may have different scores. PMsearch uses a dynamic programming algorithms to find the alignment with the highest score. ( ) ( )1( , ) ( , )kz i t j t g a p g a ptS a b s a b n l ??? ? ? ??How Alignments Are Determined And Scored For the alignment to get to (m,n), it must go through one of: (m1, n1) (am and bn are a match), (m1, n) (meaning (m,n) is in a gap in sequence 2), (m, n1) (meaning (m,n) is in a gap in sequence 1). Recursion: For i = 1 to m For j = 1 to n H(i,j) = max {H(i1,j1)+s(i,j), Hh(i,j), Hv(i,j)}, where Hh(i,j) = max {Hh(i,j1)δ, H(i,j1)δΔ } Hv(i,j) = max {Hv(i1,j)δ, H(i1,j)δΔ } End End PMsearch sample output: list of hits PMsearch Path Metrics [20Sep2022] [Build linux x86 30Jul1998] Reference: US Patent Pending, Methods for Establishing Pathway Database and Performing Pathway Searches. Y. Yang, C. Piercy. February 20, 2022. Application number 60/269,711. Query= hsa00625 (5 proteins) PW Database= keggall 4,881 pathways。 for $file ($q_pw, $q_aa, $aa_db) { if (!(e $file)) { die Did not find $file file\n。 } close (QSEQ)。}} close (AA)。 }else{ $total_score{$gn2spec{$arr[1]}} = $arr[2]*20。 $i++) { my (ln1, ln2, ln3, $sc, $hid, $k)。} push (ln1,$q[$k])。 my ($bg, $end,$hsp_len,$pm_score)。 ($l, $tp) = split(/:/, $arr[6])。 system (sort k 3rn /tmp/$$.matrix /tmp/$$.)。 print \n。 while (DB) {if ($_=~/Total keys\s(\d+)/) {$aa_nu=$1。}} close (DB)。 print Ref.: US . \Methods for Establishing Pathway Database\n。 } sub get_pm_score { my ($pct_id, $pct_pos, $hsp_len, $q_len, $m_len) = _。 $hsp_len = abs($end$bg)+1。 open (IN, /usr/local/biobin/im_cycle blastp $aa_db $q_aa S=100 | /usr/local/biobin/pm_pblast |)。 push (ln3, $hid)。 $j6。 my ($qid, $i, $j, $ln)。 while(MAT) { chomp。 amp。 while (QSEQ) { $file=$_。 Part 1. Parse input, check files my ($usage, $q_id, $q_aa, $q_pnu, $q_pw, $aa_db)。 D Hyseq Pharmaceuticals, Inc. Sunnyvale, CA, USA Singapore National University January, 2022 Definition of Bioinformatics ? Theoretical The essence of life is information. Bioinformatics is the study of the information content of life. ? Practical The essential tool is puter. Bioinformatics is puterbased information abstraction and processing of biological knowledge. Pathways ? A schematic diagram of a proteinprotein or proteinmolecule interaction pathway A circle indicates a protein or a nonprotein biomolecule. An arrow indicates the direction of proteinprotein interaction or proteinmolecule interaction. Pathway Database Increasing Level of Complexity ? The genome – 4 bases – 3 billion bp total – 3 billion bp/cell, identical ? The proteome – 20 amino acids – ~60K genes, ~200K proteins – ~10K proteins/cell。 $usage = \n $0 query_pw query_aa protein_db\n query_pw: query pathway file query_aa: query aa file protein_db: protein db to search\n\n。 next。big_matrix_sort($aa_db, $q_aa)。} $qu2spec{$arr[0]}{$gn2spec{$arr[1]}} = $arr[1]。 printf Hit%3d: Ortholog pathway for: %20s. With score: %\n\n, $ii,$spec, $total_score{$spec}。 if ($qu2spec{$q[$k]}{$spec}) {$hid=$qu2spec{$q[$k]}{$spec}。print_end。 arr = split(/\t/)。 } printf HIT %s\t%s\t%\n, $arr[0],$arr[1],$pm_score。 return 1。 print ($q_pnu proteins)\n\n