{"id":"https://openalex.org/W4416393165","doi":"https://doi.org/10.48550/arxiv.2510.07337","title":"Decoding the dark proteome: Deep learning-enabled discovery of druggable enzymes in Wuchereria bancrofti","display_name":"Decoding the dark proteome: Deep learning-enabled discovery of druggable enzymes in Wuchereria bancrofti","publication_year":2025,"publication_date":"2025-10-07","ids":{"openalex":"https://openalex.org/W4416393165","doi":"https://doi.org/10.48550/arxiv.2510.07337"},"language":"en","primary_location":{"id":"pmh:oai:arXiv.org:2510.07337","is_oa":true,"landing_page_url":"http://arxiv.org/abs/2510.07337","pdf_url":"https://arxiv.org/pdf/2510.07337","source":{"id":"https://openalex.org/S4393918464","display_name":"ArXiv.org","issn_l":"2331-8422","issn":["2331-8422"],"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"text"},"type":"preprint","indexed_in":["arxiv","datacite"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://arxiv.org/pdf/2510.07337","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Shivakumar, Shawnak","orcid":null},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Shivakumar, Shawnak","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5020532591","display_name":"J. Javier Hern\u00e1ndez","orcid":"https://orcid.org/0000-0001-6735-4303"},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Hernandez, Jefferson","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12254","display_name":"Machine Learning in Bioinformatics","score":0.44830000400543213,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12254","display_name":"Machine Learning in Bioinformatics","score":0.44830000400543213,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12576","display_name":"vaccines and immunoinformatics approaches","score":0.14100000262260437,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11103","display_name":"Antimicrobial Peptides and Activities","score":0.04340000078082085,"subfield":{"id":"https://openalex.org/subfields/2404","display_name":"Microbiology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/druggability","display_name":"Druggability","score":0.6825000047683716},{"id":"https://openalex.org/keywords/drug-discovery","display_name":"Drug discovery","score":0.5602999925613403},{"id":"https://openalex.org/keywords/chembl","display_name":"chEMBL","score":0.5508000254631042},{"id":"https://openalex.org/keywords/wuchereria-bancrofti","display_name":"Wuchereria bancrofti","score":0.4763999879360199},{"id":"https://openalex.org/keywords/proteome","display_name":"Proteome","score":0.4189999997615814},{"id":"https://openalex.org/keywords/enzyme","display_name":"Enzyme","score":0.41429999470710754},{"id":"https://openalex.org/keywords/ensembl","display_name":"Ensembl","score":0.3978999853134155},{"id":"https://openalex.org/keywords/pubchem","display_name":"PubChem","score":0.36149999499320984}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.7491999864578247},{"id":"https://openalex.org/C10679952","wikidata":"https://www.wikidata.org/wiki/Q5308937","display_name":"Druggability","level":3,"score":0.6825000047683716},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5950999855995178},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.5602999925613403},{"id":"https://openalex.org/C63222358","wikidata":"https://www.wikidata.org/wiki/Q6120337","display_name":"chEMBL","level":3,"score":0.5508000254631042},{"id":"https://openalex.org/C2778672586","wikidata":"https://www.wikidata.org/wiki/Q311109","display_name":"Wuchereria bancrofti","level":4,"score":0.4763999879360199},{"id":"https://openalex.org/C104397665","wikidata":"https://www.wikidata.org/wiki/Q860947","display_name":"Proteome","level":2,"score":0.4189999997615814},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.41429999470710754},{"id":"https://openalex.org/C141674004","wikidata":"https://www.wikidata.org/wiki/Q1344256","display_name":"Ensembl","level":5,"score":0.3978999853134155},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3702000081539154},{"id":"https://openalex.org/C158180186","wikidata":"https://www.wikidata.org/wiki/Q278487","display_name":"PubChem","level":2,"score":0.36149999499320984},{"id":"https://openalex.org/C94795543","wikidata":"https://www.wikidata.org/wiki/Q3813754","display_name":"Human proteome project","level":4,"score":0.36039999127388},{"id":"https://openalex.org/C2779997623","wikidata":"https://www.wikidata.org/wiki/Q311376","display_name":"Plasmodium vivax","level":4,"score":0.3601999878883362},{"id":"https://openalex.org/C168831097","wikidata":"https://www.wikidata.org/wiki/Q413248","display_name":"Depsipeptide","level":2,"score":0.35569998621940613},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.35499998927116394},{"id":"https://openalex.org/C202264299","wikidata":"https://www.wikidata.org/wiki/Q905695","display_name":"UniProt","level":3,"score":0.35190001130104065},{"id":"https://openalex.org/C10010492","wikidata":"https://www.wikidata.org/wiki/Q3142557","display_name":"Protein sequencing","level":4,"score":0.3188999891281128},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.31619998812675476},{"id":"https://openalex.org/C54174078","wikidata":"https://www.wikidata.org/wiki/Q3197188","display_name":"Kinome","level":3,"score":0.2833000123500824},{"id":"https://openalex.org/C149034497","wikidata":"https://www.wikidata.org/wiki/Q1384835","display_name":"Expressed sequence tag","level":4,"score":0.28060001134872437},{"id":"https://openalex.org/C167625842","wikidata":"https://www.wikidata.org/wiki/Q899763","display_name":"Peptide sequence","level":3,"score":0.27880001068115234},{"id":"https://openalex.org/C155261790","wikidata":"https://www.wikidata.org/wiki/Q1122544","display_name":"DrugBank","level":3,"score":0.2745000123977661}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:arXiv.org:2510.07337","is_oa":true,"landing_page_url":"http://arxiv.org/abs/2510.07337","pdf_url":"https://arxiv.org/pdf/2510.07337","source":{"id":"https://openalex.org/S4393918464","display_name":"ArXiv.org","issn_l":"2331-8422","issn":["2331-8422"],"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"text"},{"id":"doi:10.48550/arxiv.2510.07337","is_oa":true,"landing_page_url":"https://doi.org/10.48550/arxiv.2510.07337","pdf_url":null,"source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I205783295","host_organization_name":"Cornell University","host_organization_lineage":["https://openalex.org/I205783295"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":null,"raw_source_name":null,"raw_type":"article"}],"best_oa_location":{"id":"pmh:oai:arXiv.org:2510.07337","is_oa":true,"landing_page_url":"http://arxiv.org/abs/2510.07337","pdf_url":"https://arxiv.org/pdf/2510.07337","source":{"id":"https://openalex.org/S4393918464","display_name":"ArXiv.org","issn_l":"2331-8422","issn":["2331-8422"],"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"text"},"sustainable_development_goals":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"Wuchereria":[0],"bancrofti,":[1],"the":[2,31,42,87,229,235,246],"parasitic":[3],"roundworm":[4],"responsible":[5],"for":[6,27,36,245],"lymphatic":[7],"filariasis,":[8],"permanently":[9],"disables":[10],"over":[11],"36":[12],"million":[13,18],"people":[14],"and":[15,77,104,129,150,170,180,182,210,217,240],"places":[16],"657":[17],"at":[19,114,194],"risk":[20],"across":[21,156,184],"39":[22],"countries.":[23],"A":[24,140],"major":[25],"bottleneck":[26],"drug":[28,78,243],"discovery":[29],"is":[30],"lack":[32],"of":[33,41,89,234],"functional":[34,232],"annotation":[35],"more":[37],"than":[38],"90":[39],"percent":[40,116],"W.":[43,63,138,236],"bancrofti":[44,237],"dark":[45,238],"proteome,":[46],"leaving":[47],"many":[48],"potential":[49],"targets":[50,192],"unidentified.":[51],"In":[52],"this":[53],"work,":[54],"we":[55],"present":[56],"a":[57,82,93,175],"novel":[58],"computational":[59],"pipeline":[60,119],"that":[61],"converts":[62],"bancrofti's":[64],"unannotated":[65],"amino":[66],"acid":[67],"sequence":[68],"data":[69],"into":[70],"precise":[71,121],"four-level":[72,111],"Enzyme":[73],"Commission":[74],"(EC)":[75],"numbers":[76,123],"candidates.":[79],"We":[80,173],"utilized":[81],"DEtection":[83],"TRansformer":[84],"to":[85,108,124],"estimate":[86],"probability":[88],"enzymatic":[90],"function,":[91],"fine-tuned":[92],"hierarchical":[94],"nearest":[95],"neighbor":[96],"EC":[97,112,122,132],"predictor":[98],"on":[99],"4,476":[100],"labeled":[101],"parasite":[102],"proteins,":[103],"applied":[105],"rejection":[106],"sampling":[107],"retain":[109],"only":[110],"classifications":[113],"100":[115],"confidence.":[117],"This":[118],"assigned":[120],"14,772":[125],"previously":[126,135],"uncharacterized":[127],"proteins":[128],"discovered":[130],"543":[131],"classes":[133],"not":[134],"known":[136],"in":[137],"bancrofti.":[139],"qualitative":[141],"triage":[142],"emphasizing":[143],"parasite-specific":[144],"targets,":[145],"chemical":[146],"tractability,":[147],"biochemical":[148],"importance,":[149],"biological":[151],"plausibility":[152],"prioritized":[153],"six":[154,191],"enzymes":[155],"five":[157],"separate":[158],"strategies:":[159],"anti-Wolbachia":[160],"cell-wall":[161],"inhibition,":[162],"proteolysis":[163],"blockade,":[164],"transmission":[165],"disruption,":[166],"purinergic":[167],"immune":[168],"interference,":[169],"cGMP-signaling":[171],"destabilization.":[172],"curated":[174],"43-compound":[176],"library":[177],"from":[178],"ChEMBL":[179],"BindingDB":[181],"co-folded":[183],"multiple":[185],"protein":[186],"conformers":[187],"with":[188,204],"Boltz-2.":[189],"All":[190],"exhibited":[193],"least":[195],"moderately":[196],"strong":[197],"predicted":[198],"binding":[199,219],"affinities":[200],"below":[201],"1":[202],"micromolar,":[203],"moenomycin":[205],"analogs":[206],"against":[207],"peptidoglycan":[208],"glycosyltransferase":[209],"NTPase":[211],"inhibitors":[212],"showing":[213],"promising":[214],"nanomolar":[215],"hits":[216],"well-defined":[218],"pockets.":[220],"While":[221],"experimental":[222],"validation":[223],"remains":[224],"essential,":[225],"our":[226],"results":[227],"provide":[228],"first":[230],"large-scale":[231],"map":[233],"proteome":[239],"accelerate":[241],"early-stage":[242],"development":[244],"species.":[247]},"counts_by_year":[],"updated_date":"2026-06-11T09:08:48.828518","created_date":"2025-10-11T00:00:00"}