{"id":"https://openalex.org/W7126091348","doi":"https://doi.org/10.1109/bibm66473.2025.11356690","title":"DiffNB: Aligning a Nanobody Diffusion Model with Direct Preference Optimization","display_name":"DiffNB: Aligning a Nanobody Diffusion Model with Direct Preference Optimization","publication_year":2025,"publication_date":"2025-12-15","ids":{"openalex":"https://openalex.org/W7126091348","doi":"https://doi.org/10.1109/bibm66473.2025.11356690"},"language":null,"primary_location":{"id":"doi:10.1109/bibm66473.2025.11356690","is_oa":false,"landing_page_url":"https://doi.org/10.1109/bibm66473.2025.11356690","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"2025 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)","raw_type":"proceedings-article"},"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5122080267","display_name":"Yikai Wu","orcid":null},"institutions":[{"id":"https://openalex.org/I24943067","display_name":"Fudan University","ror":"https://ror.org/013q1eq08","country_code":"CN","type":"education","lineage":["https://openalex.org/I24943067"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Yikai Wu","raw_affiliation_strings":["Human Phenome Institute, Fudan University,Shanghai,China"],"affiliations":[{"raw_affiliation_string":"Human Phenome Institute, Fudan University,Shanghai,China","institution_ids":["https://openalex.org/I24943067"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5124153741","display_name":"JiaShu","orcid":null},"institutions":[{"id":"https://openalex.org/I183067930","display_name":"Shanghai Jiao Tong University","ror":"https://ror.org/0220qvk04","country_code":"CN","type":"education","lineage":["https://openalex.org/I183067930"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"JiaShu","raw_affiliation_strings":["Shanghai Jiao Tong University,Computer Science and Engineering,Shanghai,China"],"affiliations":[{"raw_affiliation_string":"Shanghai Jiao Tong University,Computer Science and Engineering,Shanghai,China","institution_ids":["https://openalex.org/I183067930"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052961032","display_name":"Dezhi Wu","orcid":"https://orcid.org/0000-0001-7152-3069"},"institutions":[{"id":"https://openalex.org/I183067930","display_name":"Shanghai Jiao Tong University","ror":"https://ror.org/0220qvk04","country_code":"CN","type":"education","lineage":["https://openalex.org/I183067930"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Dezhi Wu","raw_affiliation_strings":["Shanghai Jiao Tong University,Computer Science and Engineering,Shanghai,China"],"affiliations":[{"raw_affiliation_string":"Shanghai Jiao Tong University,Computer Science and Engineering,Shanghai,China","institution_ids":["https://openalex.org/I183067930"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5124295258","display_name":"Yiming Qin","orcid":null},"institutions":[{"id":"https://openalex.org/I4210153550","display_name":"Beijing Tsinghua Chang Gung Hospital","ror":"https://ror.org/050nfgr37","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210153550"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yiming Qin","raw_affiliation_strings":["School of Clinical Medicine, Tsinghua University,Beijing Tsinghua Changgung Hospital,Beijing,China"],"affiliations":[{"raw_affiliation_string":"School of Clinical Medicine, Tsinghua University,Beijing Tsinghua Changgung Hospital,Beijing,China","institution_ids":["https://openalex.org/I4210153550"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5123719797","display_name":"Tobias Pl\u00f6tz","orcid":null},"institutions":[{"id":"https://openalex.org/I164928964","display_name":"Merck (Germany)","ror":"https://ror.org/04b2dty93","country_code":"DE","type":"company","lineage":["https://openalex.org/I164928964"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Tobias Pl\u00f6tz","raw_affiliation_strings":["AI&Quantum Lab, Merck KGaA,Darmstadt,Germany"],"affiliations":[{"raw_affiliation_string":"AI&Quantum Lab, Merck KGaA,Darmstadt,Germany","institution_ids":["https://openalex.org/I164928964"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5124150004","display_name":"Karin Hrovatin","orcid":null},"institutions":[{"id":"https://openalex.org/I164928964","display_name":"Merck (Germany)","ror":"https://ror.org/04b2dty93","country_code":"DE","type":"company","lineage":["https://openalex.org/I164928964"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Karin Hrovatin","raw_affiliation_strings":["Digital Chemistry, Merck KGaA,Darmstadt,Germany"],"affiliations":[{"raw_affiliation_string":"Digital Chemistry, Merck KGaA,Darmstadt,Germany","institution_ids":["https://openalex.org/I164928964"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5116594287","display_name":"Stephanie M. Linker","orcid":null},"institutions":[{"id":"https://openalex.org/I164928964","display_name":"Merck (Germany)","ror":"https://ror.org/04b2dty93","country_code":"DE","type":"company","lineage":["https://openalex.org/I164928964"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Stephanie M Linker","raw_affiliation_strings":["Digital Chemistry, Merck KGaA,Darmstadt,Germany"],"affiliations":[{"raw_affiliation_string":"Digital Chemistry, Merck KGaA,Darmstadt,Germany","institution_ids":["https://openalex.org/I164928964"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5124210292","display_name":"Alexander Vincent Hopp","orcid":null},"institutions":[{"id":"https://openalex.org/I164928964","display_name":"Merck (Germany)","ror":"https://ror.org/04b2dty93","country_code":"DE","type":"company","lineage":["https://openalex.org/I164928964"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Alexander Vincent Hopp","raw_affiliation_strings":["AI&Quantum Lab, Merck KGaA,Darmstadt,Germany"],"affiliations":[{"raw_affiliation_string":"AI&Quantum Lab, Merck KGaA,Darmstadt,Germany","institution_ids":["https://openalex.org/I164928964"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012135043","display_name":"Mathias Winkel","orcid":"https://orcid.org/0000-0002-0345-9701"},"institutions":[{"id":"https://openalex.org/I164928964","display_name":"Merck (Germany)","ror":"https://ror.org/04b2dty93","country_code":"DE","type":"company","lineage":["https://openalex.org/I164928964"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Mathias Winkel","raw_affiliation_strings":["AI&Quantum Lab, Merck KGaA,Darmstadt,Germany"],"affiliations":[{"raw_affiliation_string":"AI&Quantum Lab, Merck KGaA,Darmstadt,Germany","institution_ids":["https://openalex.org/I164928964"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069474722","display_name":"Philipp H. P. Harbach","orcid":null},"institutions":[{"id":"https://openalex.org/I164928964","display_name":"Merck (Germany)","ror":"https://ror.org/04b2dty93","country_code":"DE","type":"company","lineage":["https://openalex.org/I164928964"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Philipp H.P. Harbach","raw_affiliation_strings":["Merck KGaA,Darmstadt,Germany"],"affiliations":[{"raw_affiliation_string":"Merck KGaA,Darmstadt,Germany","institution_ids":["https://openalex.org/I164928964"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5052221471","display_name":"Feng Tan","orcid":"https://orcid.org/0009-0001-4754-4641"},"institutions":[{"id":"https://openalex.org/I164928964","display_name":"Merck (Germany)","ror":"https://ror.org/04b2dty93","country_code":"DE","type":"company","lineage":["https://openalex.org/I164928964"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Feng Tan","raw_affiliation_strings":["AI&Quantum Lab, Merck KGaA,Darmstadt,Germany"],"affiliations":[{"raw_affiliation_string":"AI&Quantum Lab, Merck KGaA,Darmstadt,Germany","institution_ids":["https://openalex.org/I164928964"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":11,"corresponding_author_ids":["https://openalex.org/A5122080267"],"corresponding_institution_ids":["https://openalex.org/I24943067"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.75107371,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":"76","last_page":"81"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.9348000288009644,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.9348000288009644,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12576","display_name":"vaccines and immunoinformatics approaches","score":0.04360000044107437,"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/T13326","display_name":"Biochemical and Structural Characterization","score":0.006200000178068876,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/sequence","display_name":"Sequence (biology)","score":0.6690999865531921},{"id":"https://openalex.org/keywords/stability","display_name":"Stability (learning theory)","score":0.6195999979972839},{"id":"https://openalex.org/keywords/generative-grammar","display_name":"Generative grammar","score":0.5627999901771545},{"id":"https://openalex.org/keywords/generative-model","display_name":"Generative model","score":0.49059998989105225},{"id":"https://openalex.org/keywords/preference","display_name":"Preference","score":0.4713999927043915},{"id":"https://openalex.org/keywords/space","display_name":"Space (punctuation)","score":0.3377000093460083},{"id":"https://openalex.org/keywords/sample","display_name":"Sample (material)","score":0.32030001282691956}],"concepts":[{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.6690999865531921},{"id":"https://openalex.org/C112972136","wikidata":"https://www.wikidata.org/wiki/Q7595718","display_name":"Stability (learning theory)","level":2,"score":0.6195999979972839},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.5751000046730042},{"id":"https://openalex.org/C39890363","wikidata":"https://www.wikidata.org/wiki/Q36108","display_name":"Generative grammar","level":2,"score":0.5627999901771545},{"id":"https://openalex.org/C167966045","wikidata":"https://www.wikidata.org/wiki/Q5532625","display_name":"Generative model","level":3,"score":0.49059998989105225},{"id":"https://openalex.org/C2781249084","wikidata":"https://www.wikidata.org/wiki/Q908656","display_name":"Preference","level":2,"score":0.4713999927043915},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.3822000026702881},{"id":"https://openalex.org/C2778572836","wikidata":"https://www.wikidata.org/wiki/Q380933","display_name":"Space (punctuation)","level":2,"score":0.3377000093460083},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.33180001378059387},{"id":"https://openalex.org/C198531522","wikidata":"https://www.wikidata.org/wiki/Q485146","display_name":"Sample (material)","level":2,"score":0.32030001282691956},{"id":"https://openalex.org/C11413529","wikidata":"https://www.wikidata.org/wiki/Q8366","display_name":"Algorithm","level":1,"score":0.31209999322891235},{"id":"https://openalex.org/C152769699","wikidata":"https://www.wikidata.org/wiki/Q410814","display_name":"Protein design","level":3,"score":0.3046000003814697},{"id":"https://openalex.org/C137836250","wikidata":"https://www.wikidata.org/wiki/Q984063","display_name":"Optimization problem","level":2,"score":0.29510000348091125},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.29510000348091125},{"id":"https://openalex.org/C165064840","wikidata":"https://www.wikidata.org/wiki/Q1321061","display_name":"Matching (statistics)","level":2,"score":0.2892000079154968},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.2856999933719635},{"id":"https://openalex.org/C34559072","wikidata":"https://www.wikidata.org/wiki/Q2334061","display_name":"Design of experiments","level":2,"score":0.266400009393692},{"id":"https://openalex.org/C18762648","wikidata":"https://www.wikidata.org/wiki/Q42213","display_name":"Work (physics)","level":2,"score":0.2621999979019165},{"id":"https://openalex.org/C147816474","wikidata":"https://www.wikidata.org/wiki/Q169525","display_name":"Protein engineering","level":3,"score":0.2612000107765198},{"id":"https://openalex.org/C126255220","wikidata":"https://www.wikidata.org/wiki/Q141495","display_name":"Mathematical optimization","level":1,"score":0.2597000002861023}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1109/bibm66473.2025.11356690","is_oa":false,"landing_page_url":"https://doi.org/10.1109/bibm66473.2025.11356690","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"2025 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)","raw_type":"proceedings-article"}],"best_oa_location":null,"sustainable_development_goals":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":15,"referenced_works":["https://openalex.org/W1956208665","https://openalex.org/W1973196098","https://openalex.org/W2095553811","https://openalex.org/W2108767516","https://openalex.org/W2160415526","https://openalex.org/W2169610187","https://openalex.org/W2953176058","https://openalex.org/W3186179742","https://openalex.org/W3195398731","https://openalex.org/W4220757565","https://openalex.org/W4386076273","https://openalex.org/W4388020856","https://openalex.org/W4402753790","https://openalex.org/W4411351778","https://openalex.org/W4412553255"],"related_works":[],"abstract_inverted_index":{"The":[0],"design":[1],"of":[2,29,83,115],"nanobodies":[3,141],"with":[4,72,96],"high":[5],"binding":[6,98,144,162],"affinity":[7,99,145,163],"for":[8,49,195,205],"a":[9,45,68,190],"given":[10],"target":[11],"is":[12,55],"the":[13,17,26,56,78,94,107,111,152,159,203],"primary":[14],"objective":[15],"in":[16,199],"therapeutics":[18],"development.":[19],"However,":[20],"existing":[21],"generative":[22,70,197],"models":[23,198],"often":[24],"sample":[25],"sequence":[27,112],"space":[28],"nanobody":[30,52,200],"without":[31],"explicit":[32],"guidance,":[33],"which":[34],"leads":[35],"to":[36,66,90,118,151,166,172,177,183],"suboptimal":[37],"affinity.":[38],"To":[39],"address":[40],"this,":[41],"we":[42,135],"introduce":[43],"DiffNB,":[44],"novel":[46,122],"diffusion-based":[47],"framework":[48],"controllable,":[50],"high-affinity":[51],"generation.":[53],"DiffNB":[54,88,109,138],"first":[57],"diffusion":[58],"model":[59,79],"that":[60,137],"leverages":[61],"Direct":[62],"Preference":[63],"Optimization":[64],"(DPO)":[65],"align":[67],"pre-trained":[69],"prior":[71],"desired":[73],"bio-physical":[74,102],"properties.":[75],"By":[76],"fine-tuning":[77],"on":[80,128],"preference":[81],"pairs":[82],"high-":[84],"and":[85,92,100,113,121,133,146,179,192,207],"low-affinity":[86],"nanobodies,":[87],"learns":[89],"characterize":[91],"generate":[93,140],"variants":[95],"higher":[97,143],"other":[101],"properties":[103],"improved.":[104],"During":[105],"generation,":[106],"DPO-aligned":[108],"co-designs":[110],"structure":[114],"CDR":[116],"regions":[117],"produce":[119],"optimized":[120],"candidates.":[123],"In":[124],"our":[125,155],"extensive":[126],"experiments":[127],"three":[129],"therapeutic":[130],"antigens(HER2,":[131],"IL-6,":[132],"CD45),":[134],"demonstrate":[136],"can":[139],"exhibiting":[142],"better":[147],"structural":[148,168],"diversity.":[149],"Compared":[150],"state-of-the-art":[153],"baselines,":[154],"DPO-guided":[156],"generation":[157],"improves":[158],"\u201cin":[160],"silico\u201d":[161],"by":[164,170,175,181],"up":[165,171,176,182],"35%,":[167],"diversity":[169],"46%,":[173],"stability":[174],"8%,":[178],"humanness":[180],"25%.":[184],"Our":[185],"work":[186],"establishes":[187],"DPO":[188],"as":[189],"powerful":[191],"efficient":[193],"paradigm":[194],"steering":[196],"design,":[201],"paving":[202],"way":[204],"targeted":[206],"accelerated":[208],"drug":[209],"discovery.":[210]},"counts_by_year":[],"updated_date":"2026-02-23T20:09:44.859080","created_date":"2026-01-30T00:00:00"}