Merge pull request #59 from gamcil/allowlocalhmm

Allow local profile HMMs

cblaster/gui/main.py

@@ -49,7 +49,7 @@ def run_cblaster(values, textbox):
         args = dict(
             query_file=values["query_file"],
             query_ids=values["query_ids"],
-            query_profiles=values["query_profiles"],
+            query_profiles=values["query_profiles"].split(";") + values["query_pfams"].split(" "),
             session_file=values["session_file"],
             mode=values["search_mode"],
             gap=values["gap"],

cblaster/gui/parts.py

@@ -4,7 +4,7 @@
 import PySimpleGUI as sg
 
 
-TEXT_WIDTH = 65
+TEXT_WIDTH = 70
 
 
 def SectionLabel(text):

cblaster/gui/search.py

@@ -119,8 +119,10 @@
             "should refer to files generated using cblaster makedb. When using any "
             "of the HMM modes, a local copy of the Pfam database will be stored at "
             "the indicated location or extracted from there. The FASTA database "
-            "should refer to the FASTA file generated using cblaster makedb.",
-            size=(TEXT_WIDTH, 6))],
+            "should refer to the FASTA file generated using cblaster makedb.\n"
+            "NOTE: you must set an e-mail using cblaster config before doing "
+            "a search with cblaster.",
+            size=(TEXT_WIDTH, 8))],
         [search_tabgroup]
     ]
 )
@@ -141,7 +143,12 @@
          sg.InputText(size=(34, 1), key="query_file"),
          sg.FileBrowse(key="query_file")],
         [TextLabel("Sequence IDs"), sg.InputText(key="query_ids", default_text="e.g. space separated values")],
-        [TextLabel("HMM profiles"), sg.InputText(key="query_profiles", default_text="e.g. space separated values")],
+        [TextLabel("Pfam domains"),
+         sg.InputText(key="query_pfams",
+         default_text="e.g. space separated values")],
+        [TextLabel("Local profile HMMs"),
+         sg.Input(size=(34, 1), key="query_profiles"),
+         sg.FilesBrowse()],
         [TextLabel("Session file"),
          sg.InputText(size=(34, 1), key="session_file"),
          sg.FileBrowse(key="session_file")],
@@ -309,7 +316,7 @@
             " at which point the figure can be manipulated and saved as SVG."
             " If a file path is specified, a static HTML file will be generated at"
             " that path.",
-            size=(TEXT_WIDTH, 4)
+            size=(TEXT_WIDTH, 5)
         )],
         [TextLabel("Output file"),
          sg.InputText(key="figure_text", disabled=True, size=(34, 1)),

cblaster/hmm_search.py

@@ -7,13 +7,15 @@
 import gzip
 import subprocess
 import logging
+import re
 
 from datetime import datetime
 from ftplib import FTP
 from pathlib import Path
+from typing import Union, List, Collection, Set, Tuple
 
 from Bio import SearchIO
-from cblaster.classes import Hit
+from cblaster.classes import Hit, Session
 from cblaster import helpers
 
 LOG = logging.getLogger(__name__)
@@ -49,27 +51,54 @@ def check_pfam_db(path):
     return hmm, dat
 
 
-def get_full_accession_number(dat_path, keys):
+def get_pfam_accession(
+    dat_path: Union[str, Path],
+    keys: Collection[str]
+) -> Tuple[Set[str], Set[str]]:
     """Get full accession number of Pfam profiles
 
+    Looks for keys in ID and AC attributes, such that accessions
+    can be retrieved by name or accession.
+
     Args:
-        keys: List, Strings of accession profiles numbers
-        db_path: String, Path to dat.gz file with the full acc-nr
+        keys: Strings of accession profiles numbers
+        db_path: Path to dat.gz file with the full acc-nr
     Return:
         key_lines: List, string of full acc-number
     """
-    valid_keys = []
+    keys = set(keys)
+    valid_keys = set()
+    name_attrs = ("#=GF ID", "#=GF AC")
     for line in gzip.open(dat_path, "rt"):
-        if not line.startswith("#=GF AC"):
+        if not line.startswith(name_attrs):
             continue
         *_, accession = line.strip().split(" ")
-        for key in keys:
-            if key in accession:
-                valid_keys.append(accession)
-    return valid_keys
+        if any(key in accession for key in keys if key not in valid_keys):
+            valid_keys.add(accession)
+    return valid_keys, keys.difference(valid_keys)
+
+
+def read_profiles(files: Collection[str]) -> Collection[str]:
+    """Reads in profile HMMs from a list of files."""
+    profiles = [] 
+    for file in files:
+        with open(file) as fp:
+            profile = fp.read()
+            profiles.append(profile)
+    return profiles
+
+
+def get_profile_names(profiles: Collection[str]) -> Collection[str]:
+    """Extracts names from profile HMMs using regular expressions."""
+    names = []
+    pattern = re.compile(r"^NAME\s+?(?P<name>\w.+?)$", re.M)
+    for profile in profiles:
+        matches = [match.group("name") for match in pattern.finditer(profile)]
+        names.extend(matches)
+    return names
 
 
-def fetch_profiles(hmm, dat, keys):
+def fetch_pfam_profiles(hmm, keys):
     """Fetch hmm profiles from db and save in a file
 
     Args:
@@ -78,26 +107,38 @@ def fetch_profiles(hmm, dat, keys):
     Return:
         ls_keys: List, strings with acc-numbers
     """
-    LOG.info("Fetching profiles from Pfam-A file")
     if not isinstance(hmm, Path):
         hmm = Path(hmm)
-
-    LOG.info("Profiles found: %s", keys)
     profiles = []
     for key in keys:
-        result = subprocess.run(["hmmfetch", hmm, key], stdout=subprocess.PIPE)
+        result = subprocess.run(
+            ["hmmfetch", hmm, key],
+            stdout=subprocess.PIPE,
+            encoding="utf-8",
+        )
         profiles.append(result.stdout)
+    return profiles
+
+
+def write_profiles(profiles: Collection[str], output: str=None) -> str:
+    """Writes a collection of profile HMMs to disk.
 
-    output = hmm.parent / datetime.now().strftime("cblaster_%Y%m%d%H%M%S.hmm")
-    with output.open("wb") as fp:
+    If no output file is specified, will randomly generate a file name and save
+    in the current working directory.
+
+    Args:
+        profiles: profile HMMs to write
+        output: name of output file
+    """
+    if not output:
+        output = datetime.now().strftime("cblaster_%Y%m%d%H%M%S.hmm")
+    with open(output, "w") as fp:
         for profile in profiles:
             fp.write(profile)
-
-    LOG.info("Saved profiles to %s", output)
     return output
 
 
-def run_hmmsearch(pfam, fasta, query):
+def run_hmmsearch(fasta, query):
     """Run the hmmsearch command
 
     Args:
@@ -108,10 +149,10 @@ def run_hmmsearch(pfam, fasta, query):
         temp_res: List, String of result file names
     """
     LOG.info("Performing hmmsearch")
-    output = query.with_suffix(".txt")
+    output = Path(query).with_suffix(".txt")
     try:
         subprocess.run(
-            f"hmmsearch --cut_tc -o {output} {query} {fasta}",
+            f"hmmsearch -o {output} {query} {fasta}",
             stdout=subprocess.PIPE,
             shell=True,
             check=True,
@@ -136,7 +177,7 @@ def parse_hmmer_output(results):
             continue
         for hit in record.hits:
             hit_class = Hit(
-                query=record.accession,  # Pfam id
+                query=record.id,  # Pfam id
                 subject=hit.id,  # Hit id
                 identity=None,  # Not present
                 coverage=None,  # Not present
@@ -149,37 +190,73 @@ def parse_hmmer_output(results):
     return hit_info
 
 
-def perform_hmmer(fasta, query_profiles, pfam, session):
+def group_profiles(profiles: Collection[str]) -> tuple:
+    """Group input query profile HMMs by Pfam, custom or invalid.
+
+    If the profile is found on disk, it will be loaded directly.
+    If not found locally, but starts with PF, will try to extract from Pfam.
+    Otherwise, marked as invalid.
+    """
+    local = []
+    other = []
+    for profile in profiles:
+        if Path(profile).exists():
+            local.append(profile)
+        else:
+            other.append(profile)
+    return local, other
+
+
+def perform_hmmer(
+    fasta: str,
+    query_profiles: List[str],
+    pfam: str,
+    session: Session,
+) -> Union[Collection[Hit], None]:
     """Main of running a hmmer search
 
     Args:
-        database_pfam: String, Path to pfam db
-        database: String, Path to seqeunce db, in fasta or gbk format
-        query_profiles: List, Pfam profiles needed to be searched
+        fasta: Path to database FASTA file
+        query_profiles: Pfam names/accessions, or paths to profile HMM files
+        pfam: Path to folder containing Pfam database
+        session: cblaster search session
     Returns:
-        hit_res: List of class objects with the hits
-
+        List of class objects with the hits
     """
     LOG.info("Starting hmmer search")
 
     # Make sure we can find hmmfetch and hmmsearch on PATH
     helpers.get_program_path(["hmmfetch", "hmmsearch"])
 
-    # Find Pfam database (.dat and .hmm)
-    hmm, dat = check_pfam_db(pfam)
+    # Divide profiles into Pfam, local files and invalids
+    local_profiles, other_profiles = group_profiles(query_profiles)
 
-    # Find real Pfam accessions
-    session.queries = get_full_accession_number(dat, query_profiles)
-
-    if not session.queries:
+    # Read in/fetch all query profile HMMs.
+    # Local profiles are just read in straight from file, Pfam accessions are
+    # extracted from a local copy of the Pfam database (require .dat and .hmm).
+    profiles = []
+    if local_profiles:
+        LOG.info("Loading local profiles: %s", local_profiles)
+        profiles = read_profiles(local_profiles)
+    if other_profiles:
+        LOG.info("Fetching accessions from Pfam: %s", other_profiles)
+        hmm, dat = check_pfam_db(pfam)
+        accessions, invalid = get_pfam_accession(dat, other_profiles)
+        if invalid:
+            LOG.warning("Failed to fetch profiles from Pfam: %s", invalid)
+        pfam_profiles = fetch_pfam_profiles(hmm, accessions)
+        profiles.extend(pfam_profiles)
+    if not profiles:
         LOG.error("No valid profiles could be selected")
         return
+    query = write_profiles(profiles)
+    LOG.info("Profiles written to: %s", query)
 
-    # Extract HMM profiles from database
-    query = fetch_profiles(hmm, dat, session.queries)
+    # Save query profile HMM names
+    session.queries = get_profile_names(profiles)
 
     # Run search
-    results = run_hmmsearch(hmm, fasta, query)
+    results = run_hmmsearch(fasta, query)
 
     # Parse results and return
     return parse_hmmer_output(results)

cblaster/plot/index.css

@@ -2,6 +2,7 @@ body {
 	margin: 0;
 	padding: 0;
 	overflow: hidden;
+	font-family: system-ui, -apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, Ubuntu, "Helvetica Neue", Oxygen, Cantarell, sans-serif;
 }
 
 .tooltip {
@@ -96,6 +97,7 @@ body {
 	max-height: 95vh;
 	border: 1px solid black;
 	background-color: white;
+	font-size: 0.9rem;
 }
 
 #div-summary {
@@ -108,8 +110,6 @@ body {
 #div-summary p {
 	margin: 0;
 	margin-bottom: 4px;
-	font-size: 10pt;
-	font-family: sans-serif;
 }
 
 #div-summary pre {

example/README.md

@@ -0,0 +1,28 @@
+## Example cblaster search
+
+In this folder you will find cblaster output generated from searching
+the burnettramic acids gene cluster from *Aspergillus burnettii*, *bua*,
+remotely against the NCBI's NR database.
+
+| File | Description |
+| ---- | ----------- |
+| ``example/bua.gbk`` | *bua* cluster GenBank file |
+| ``example/bua.fasta`` | FASTA file containing proteins in *bua* |
+| ``example/bua_session.json`` | cblaster session file |
+| ``example/bua_binary.txt`` | Binary absence/presence table output |
+| ``example/bua_summary.txt`` | Default results summary |
+| ``example/bua_results.html`` | Interactive output visualisation |
+
+These files were generated with the following command:
+
+	cblaster search \
+		--query_file bua.gbk \
+		--session bua_session.json \
+		--binary bua_binary.txt \
+		--output bua_summary.txt \
+		--plot bua_results.html
+
+Searching with the GenBank file allows for synteny scoring of detected clusters.
+However, you could also search with the FASTA file by specifying:
+
+	--query_file bua.fasta

example/bua.fasta

@@ -0,0 +1,18 @@
+>QBE85641.1
+MPGQKPVVLFLTNSEFGQSSVVLAVAQELVRQSACEVHVASFSALKQQVEALNVAFHALPGRSMKEALCDSGLPFLPKHAPGTRGAVESYRKGLQHVVAPWEPAGYEPIYRACLDLLDKLNPDLVAVDPLFGPGQDACNVRQCRYLVLSPASFKDHLVQVQPHLRVLWKYPVISSGLPCPLPLFLIIINFYLIFKLVLHTFLSKRVQTLTKWRNHIGIPGDLTTIYANFNEKVPWLLPSIPQSDFPLKIPTNVTGCGPIIPPFESVAHNPTASWLAQRPTILFNLGSHMKYKLTDAQQVVTALSMVLHTYPDMQILWKCELSHDDPSSKEPESSDSSAIQDLIPAELTDRIRVTSWITPSPMSILAHDSTIMYVHHGGSNSFHEALAAGVAQVVCPVWLDTYDVAARVEFLRVGLRGNGKAAPHLEGSELGAAICRTAHRLRSGDMGTRTRELQAHILAQEEGVSGTGPADVYGVGRRKAAKVILDMITA
+>QBE85642.1
+MGIQHMLPSTQTAIIAGPQGEFQLSHDVPVTPLADDEIIMKTAAVALNPVDTKLVGDFITPGAIFGFDCAGVIVAVGPKVGNGLAIGDRVCGSARGMNREKPLGGAFAEYVMLPADLTLRIPPAMTFAEAASLGTALVSACMSLFWTMQIPASLQEPAEKPFPVLVYGGSTATGTMLLQVLKICGVRTLTTCSPKNFDLVRSYGADEVFDYNSPTCAQDIREATRNNLKYAVDCITEDSTIKICYSAIGRAGGQYIALNPYPEHLATRKVIKPGWILATLITGEGSAWPEPYHREPDPEIRALAKPAYSAVQKLLDEGRLRSHPIRVKDGGLAAVLDGVEVLRKGEISGQKLVYCFN
+>QBE85643.1
+MLVPVLTLLGTLTATGTLVYHFDERLPVVRFRLLTTFLVLSSGQLLLYALWKVFLKPLCFSPFKHLPKPPLDQWPLWRDHEDGQRGGRAQVGIIHCRGILNGERLIVSSPTALAKIASDNYTFIKPMAIKLLAGRVLGMGLVLTERDEHKQQRKLFLPPFAPKHIRDLYPTFWRKSREVTERMGDEIHATGAGNGVFEIGEWAARVALDIITLSTMGKDFGSVRDADAPLAKVYHTVLQPTLGHVVIAVLKNFLPARLVEALPLRSNRHQGDAYDTIRGVCRDLLREKKDQLAGHHLGGKDILSVCLRYEDIAGVDEEEVINQMTTILGAGHETISVGITWAIYMLCLHRDWQARLREEVRATLPSPDRAQESASSADVERMPLMRAFLEEVLRWYPPIPMTMREPLVDTELDGQYVPRGTRIVVPIKAINREERYWGPDAKRFSPSRWLKNDREFNPSGGVSSKYGYLSFMHGPRSCVASEFARAEMACVVSAWVGRFDLDLSDEHFRDEENMRTSNGNFSGKPLEGLYVRAQVLEGW
+>QBE85644.1
+MTTPVKGTSPGPDEWHHLEDLNQRRRIQNRLSQRNRRTNLRNQVAQGQKQETAKHSEPKQNRQLFWVPPNSSTAKGKLVTTKGNKLESPRPPDPVTPPGRWPEIWHASLHEKPSGGALHGDLGDDMDSCWINTLIRSPVLPIDDDMLSCTPPIPTFDTTMTLDAAPVPTAMPVRDGGLSEGNTTHIQVPSANGVELGRTGGCKAPQDMHFTVQPQQPMTSIHTDKDRRDHFFGYAALHVAASRGHLAVVQLLTERGIPVDQLSSENETALHLAAEQGHCAVAHYLLERGADPHRGNQYGETALHVAAGHGHCDIVRLLFSYLPDLNIVDRNGHTALLRAVAEGHVDVVRVLLERGMDAGMKVGWPLDQKSI
+>QBE85645.1
+MEVERLDYTDFLNEAPGRQEAFVQHLYAALSRVGFAKITNHPIPESVILQLFAWTKGFFTLPLEHKRKAAHPPQPNPHRGWSCIGQEKLSVIAQGKAVLDLKESFDMGPGDDELYPNIWTDEGDLPGFRAFMEDFYGRCQSLHLQLLSAIARSMQLPDSYFAPLCSQNSSELRLNHYPAVSRHDLTTGTMRISSHTDFGTITLLFQDSVGGLEVEDQTRPGHYMPVAADDCTDIIVNVGDCLQRWTNDRLRSANHRVTLPRGLTHGMVDDRYSIAYFGKPSRDVSVRTLSALLRANEEAKYREEMTAWQYNQSRLLQTY
+>QBE85646.1
+MAIASSIGLVAEAIHRHKTPERPIESENDIARYPAEDEQWALDELQDELCQEEPSDSEDQPKKKIRNPAKLADDFLKRYPPPPSGSAPAGRLPLPVIIPQRRPGVRVRGFVRAYAPDLQACGIDQDTFMDFLVTMTRAGRAPQWMGAANLTAAAAFALPGHAIGCGVGFAIQVVNAIAMEMRGRVQANGFLQKLNQGFFQPRGLYCLVLSFDNTHEEAMTDESLATAIATTTDPKTGVRKYTDKLRSHSGTTGPSEFPESAPLVFPVLDWLETNANAEQAEKLGRYKKFRKFVADYYDRRAQAEYAARNPTSPLAAPPRRGFTSKLADPNDDTNKSPISLATGGLVPYNTTWRETRNSEGRRPPRKIADKVLYMIIVNMPSDDDMSRAESIMATEATTEPSVQSDDAEAAKG
+>QBE85647.1
+MFLLILYAFLTAVVARKLSAAVSVYRYRKMHGLLLARPLNQKGDVIGFSLFRGMQKSAREGLSLQRHYENTQQHGPTISAVLLGKSFISTSDPENIKAVLATQFQDFNLGERNDAFAPFLGRGIFTEDGPEWERSRALIRPSLSKAQVAELPIIEQHVQNLLSRIPGDGSTVDLQQLFFNFTLDSATHSLLGQPVGFQLSPAGSEAERFSRAFDDAQAFLQVRAKLGPFRGLVRNKAFEVNCQLVHSAVDRYVSEALGRSARPRSEDGKPGSMRYDLLSELASTMTDRTQIRNELLNVLLAARDTTASLLSSVFFMLARHPRVWSRLQQEVVQLEGQRPTYDKLREMRYVRAVLNEALRLFPPVPTNIRCATCHTSLPRGGGVDGLQPVFVANGTIVHYSIWTMHRSTAIYGSDAEEYRPERWLQESDEAPLRPGWGFLPFSGGPRICLGQQKALTEAAYVVIRMLQTFATVQSRDQRPWREHMGLVLSSFHGVQVALRHVEG
+>QBE85648.1
+MAAPTEVTLRNLSGTWTLSSSLSDDPSPALELQDVSWLVRNVIANAPVTISITQTVDPTTGVTKIASTQSTLGRTVSDVRYLEWEVEDQQNHPLFGSLSMRSRWAKASDLGEGFLIGNADGEAELIEVLAHGTMAGWTSHQVWAFEEIDGHRYHTRRALVTKGDQQVQVRMVYDWQTEE
+>QBE85649.1
+MAPQNEPIAIVGSGCRFPGEASSPSKLWDLLREPRDVLSKIDRFSADGFYNKDGHHHGSSNVLHSYQLSEDTRSFDAQFFNIPASEAESMDPQQRFIMEVVYEALESAAIKIEELSGSPTAVYVGVMCNDYAHITYADLESVPKYAATGTALSILANRISYFFNWTGPSMTIDTACSSSLVALHHAVQTLRGGTSKVAVAAGTNLIFTPTNYIAESNVNMLSPTGRSRMWDANADGYARGEGVAAVVLKTLSQAVADGDRIECVIRETGLNQDGRTPGITMPSSVAQAELIRSTYARAGLDVTRESDRPQFFEAHGTGTKAGDPEEAKAIYKAFFGQEDTMDARDTLYVGSIKTIIGHTEGTAGLAGLLKASLAVQNKTLPPNMHFHTLNPDIEPYYGKLQILTSVKPWPALASGVPRRVSVNSFGFGGANAHAIVESYEPSNGAIKVQSSKETAIPFTFSGYSEKSLMSQLTSFLEYLDSHPEPRLRDSAWTLSRRSAFSTRTTVSGTSIERLQEKLQSKIDSKIKDGKALGIRSSSKNDKILGVFTGQGAQWPRMGLRLLQSSATARRIFDDLERSLAELPTEDRPSWSLVQELEREAEDSRVMEAEFSQVLCTAVQVMLVDLLHSVGVSFDIVVGHSSGEIGAAYSAGYLSARDAIRIAYYRGKFGKLACGRDGVAGGMLAAGTDMADAKDLCELDDFVGRLQLAASNSSSSVTLSGDAEAVAWAQFVLEDEKKFARLLKVDTAYHSYHMQPCAEPYIEAMKRAGIQALKPQSDCRWFSSVLEGQEVSAAMSASLANSYWRDNLLQPVMFSQALEQAVSNTSDIGLVLEVGPHAALRGPATLTINDKLGRDVPYFGLLSRNADDVESFSDGIGAVWASLARCVIDFTRVDALLADGPEDQPRLCDNVPGYSWDHQRTYWMESRSSAALRLRPAAHHELLGVRVDSLNREYRWRNFIKPSQLSWTRGHQVQSQLIFPGAGFSVMALEAAKALAPAEKIALVELTDMQVLRAMAFQDENTAVEVICSLSNVIEDPDQANLTANFTCDMCLSKESGFVMAACGAVRLQLGAASSQLLPERTACPVRMNDVNIEHFYSTLWSLGYNYTDMFRSITSLQRTTDAASGIIHTTTEPDYTTSLTLHPATLDVAFQGIFGAMGAPGDGRLWTVLVPTRIKRITINPAVCGGTSGLGVDLPFDASVSVSPIDGVAGDVDIFDSTGVNKAVQVEGLQVAPLVPVTQSDDREVFSDTIWNFQEPDAARDVPKWTLTDEEWEHARYVERACFYYLKQLHDTITAEERDRCEWHPRKMLDWATEVVGVVSRGEHPIIRQEWMNDTWEMLKGPLDELTAKYEDFESLTHVGKNLIPFVKGEFSLLELVRNGGLLEHIYRNTYAFCEYNNYLANLVKQLSHRFPRMDIFEIGAGTGSTTEAVLRGIGDHYSSYTYTDLSAGFFPNAQETFKEHDAKMIYKIYDAEKEPGKQGYTERTYDLVIASNVLHATHSLETTLTNARKLLKPGGYLVMLEVTDVNPLRPTFFFGCLPGWWVGENDGRPHHPLVTKERWGELFDRTGFSGLDTSTPSHDVFMAPFSVMLTQAVDRQMALIRQPLQEDNRTTIDHLLILGGTGFTSFMLIEDVKHQLKRYAKHVIVVETLEALEASHFHSRQMLLSLVELDAPVFSPFTPERFAALQMLTEKCRNVLWVVRGASGEQPYANMMNGVARCLVGEQPDMRFQFVDFDMADKVDAGFIVRSLLQLQISDAWHTFIEPYRPVWTLEREVRYIQGQAHIPRYSPSLRRNLQYNSWRRTIRETVDPSSKYVILTHANGYYDLEEDNSPRPDPMAEDDRMAINVSRSSTVAVEIDGIGHLYILTGECELSGQRVLAFSSHNASRVQVKKDWVVSIGILSSDEPALIQMVTNVCLGTMLLNQTPRNGSLLVYEPTVALARILTALTSAEEPGRVLFTTTNRAKLDSGVAFSFIHPSSPDSSIARWVPAGVAGFVDASGGRKEQNMAARFARHLSSQCRVISMEGFYSNSSHQWGNAGGNSLSALLQHSTGLFTQGYKQCKQNQVQELSLDDVIGASTEHKEIRILNWKSQSKALVKLSPVQDEITFKGDRTYLLVGLTGELGRSLCRWMVQRGARYVVLTSRKPDVEPAWLELMQSYGAHIEVMAMDATDRKSTYNTVRKVQQTLPPVAGVGNGAMVLNDGLFNVISHQDFNQTLRPKVDGTTYLNELFQSPDLDFFIVFSSLAYVTGNFGQTSYAAANAFMASLVEGRKRRGLPGSVMNLAGIFGLGYITRTDRSILERLGKLGYANISEYDFHQFFAEAVLSGVPGSGRCHEISSALRPIDPDGETNPPAWLDMPRLSYYRHTKHAFTESGDTKSLSVRSQLKEQTTMEDVQRVLTNGLILTLYKQLGLDPEDDAISPDTSLVELGIDSLVAVDMRVWFTKELDLDMPVLKLLGGATVAAMVEDTMERMSPDLIPNVAQKDVTVAADRPSAPSDGVPAVGRSTAVSTTEHNSEEQESHAMETQELDESTTSGGECSSTKESSSSEATPPPSSVMSEDLAKVEETASIDGPKYVRKVKMGYGSLQFFFLVKHLDDPTVLNMQFRLPLQGSIKIPDLKYAVKMLGQRHEALRTAFFVDAENDDEPTQGVLETSPLQLETMQVTDSKEARRVCEDVQKYVFNIESGETIRILLLSITPSSHWLVLSFHHISIDGFSFNILLDEINALYQGQHLPPVKTQFTDVMCKQRQDLQAGFRRSELAYWQQVLGKIPDPIPLFPVAKLSSRLPVTRYHFEEAPMASIDAATAEQIRKQCRALKATRFHFFMTVLRIFLFAFLDTDELCIGFADASRADSGVSRTVGYLVNMLSLKFQRKPSQTFAQKVEEARKQSYAALANSTVPFNALLEKLEPPRSAAYTPVFQVFMDYLQHKFTAPKGLGVVEEQVYAHLTHNFFDLAVDINDVSASEILVRFRMQQYLYSASSVSLLLKSYVQLVKMCAYMEPNKAIGEPVPYDAQDIERAISLGQGPVVSSQWPSTPIERILDVAQARPEAPALVDGEGARLSYMEMIDRAHSIAGCLLTAGVAEGSTVGVYQEPTADSICSLLAIWIIGAVYLPLDRRVPCSRLSSIVQDCQPSAILCHERTLSDTPYLEATKQTAIITVPVNVAGIEAAPVPLNTGNGDQTSIILYTSGSTGVPKGLPIRHVSLLNQIEAMTTTFGVGAEMVLQQSAPSFDVSMQQILMALCNGGALYVVPNETRLDPVTITRLIASEKITWVHATPSEFTQWLRHGSAHLRAAKDWKFAFSSGEALSSDLVKGFEALRRPDVKLINVYGPAEAGVITGTEIDTTHVSAEPRSPISLGSPLANIAVYVVDRNLRPVPVGVSGEIVVAGAGNISGYLNRFELTAKLFLPDTITPRGYYPGQLATLYRSGDIGRYSPDGQLYYEGRIAGDTQVKLNGIRIDLKDVESAILETSGGEIVNAIVTDRRSPDFLVAHVELKADFPEAERKNFLTYIQQCLPLPKYMCPAMFIPLDHVPLNSHGKLDRRAIAARPLPTVDGDDQQGDADLSETELALRELWTGCLPEDVVKLTSISATTDFFHLGGNSYLLVRLQRLIRDRFNVSVPVMALYDASTLMAMALKIRNSQSLAVIDWDTETSVAQSLGASPCAEQPTAPRKTTDLTVVLTGATGYLGSRIMKALIASEQVSQIHCVAVRGHSAGVPRELAHSSDKLILHGGHLEDPLLGMSEEEFTFVARETDLVIHSGANRSFWDHYERLRGPNVLSTKTLVDLALQNQAPLHFISSGGVHLLCSGEDYAAESLASYLPPTDGSNGYIASKWASEVYLEKAAQKTSLPVYVHRLTPAPDVTPDAPMELLEEMSALAVKLQALPAPSGWTGTFDLTPAEALATGIAAAAVGAQAPMLESHQSARFIHHPSQVKMTMDHVAKYLDMLPSAEGFERLPPLQWAGRAKREGLTWHFSSTDFITMGG