{"id":"https://openalex.org/W7203780767","doi":"https://doi.org/10.64898/2026.08.14.744988","title":"Response representation shapes AlphaGenome enhancer-gene prediction in human astrocytes","display_name":"Response representation shapes AlphaGenome enhancer-gene prediction in human astrocytes","publication_year":2026,"publication_date":"2026-08-19","ids":{"openalex":"https://openalex.org/W7203780767","doi":"https://doi.org/10.64898/2026.08.14.744988"},"language":"en","primary_location":{"id":"doi:10.64898/2026.08.14.744988","doi":"https://doi.org/10.64898/2026.08.14.744988","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.14.744988","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.64898/2026.08.14.744988","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5068182723","display_name":"Zhongwei Huang","orcid":"https://orcid.org/0000-0002-4061-9321","observed_orcids":["https://orcid.org/0000-0002-4061-9321","https://orcid.org/0009-0003-4163-2020"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Zhongwei Huang","raw_affiliation_strings":["Department of Bioengineering, University of Washington, Box 355061, Seattle, WA 98195-5061, USA"],"raw_orcid":"https://orcid.org/0009-0003-4163-2020","affiliations":[{"raw_affiliation_string":"Department of Bioengineering, University of Washington, Box 355061, Seattle, WA 98195-5061, USA","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111086046","display_name":"Ruohan Huang","orcid":"https://orcid.org/0009-0007-8244-739X","observed_orcids":["https://orcid.org/0009-0007-8244-739X"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ruohan Huang","raw_affiliation_strings":["Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA"],"raw_orcid":"https://orcid.org/0009-0007-8244-739X","affiliations":[{"raw_affiliation_string":"Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5146997707","display_name":"Jinquan Han","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jinquan Han","raw_affiliation_strings":["Department of Bioengineering, University of Washington, Box 355061, Seattle, WA 98195-5061, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Bioengineering, University of Washington, Box 355061, Seattle, WA 98195-5061, USA","institution_ids":["https://openalex.org/I201448701"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5068182723"],"corresponding_institution_ids":["https://openalex.org/I201448701"],"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/T10222","display_name":"Genomics and Chromatin Dynamics","score":0.986299991607666,"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/T10222","display_name":"Genomics and Chromatin Dynamics","score":0.986299991607666,"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/T10878","display_name":"CRISPR and Genetic Engineering","score":0.002400000113993883,"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/T10261","display_name":"Genetic Associations and Epidemiology","score":0.00139999995008111,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/human-astrocytes","display_name":"human astrocytes","score":0.7580000162124634},{"id":"https://openalex.org/keywords/crispr-interference","display_name":"CRISPR interference","score":0.8119999766349792},{"id":"https://openalex.org/keywords/alphagenome","display_name":"AlphaGenome","score":0.7009999752044678},{"id":"https://openalex.org/keywords/rank-fusion","display_name":"rank fusion","score":0.6700000166893005}],"concepts":[{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.6794999837875366},{"id":"https://openalex.org/C112313634","wikidata":"https://www.wikidata.org/wiki/Q7886648","display_name":"Complement (music)","level":5,"score":0.573199987411499},{"id":"https://openalex.org/C2778067643","wikidata":"https://www.wikidata.org/wiki/Q166507","display_name":"Interval (graph theory)","level":2,"score":0.5055999755859375},{"id":"https://openalex.org/C111936080","wikidata":"https://www.wikidata.org/wiki/Q913367","display_name":"Enhancer","level":4,"score":0.4650999903678894},{"id":"https://openalex.org/C165838908","wikidata":"https://www.wikidata.org/wiki/Q736777","display_name":"Calibration","level":2,"score":0.42500001192092896},{"id":"https://openalex.org/C44249647","wikidata":"https://www.wikidata.org/wiki/Q208498","display_name":"Confidence interval","level":2,"score":0.42410001158714294},{"id":"https://openalex.org/C153180895","wikidata":"https://www.wikidata.org/wiki/Q7148389","display_name":"Pattern recognition (psychology)","level":2,"score":0.3937999904155731},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3783999979496002},{"id":"https://openalex.org/C2776401178","wikidata":"https://www.wikidata.org/wiki/Q12050496","display_name":"Feature (linguistics)","level":2,"score":0.3774000108242035},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3569999933242798},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.3425000011920929},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.3352000117301941},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.3343999981880188},{"id":"https://openalex.org/C87117476","wikidata":"https://www.wikidata.org/wiki/Q362383","display_name":"Cardinality (data modeling)","level":2,"score":0.30720001459121704},{"id":"https://openalex.org/C25343380","wikidata":"https://www.wikidata.org/wiki/Q277521","display_name":"Relation (database)","level":2,"score":0.3066999912261963},{"id":"https://openalex.org/C117220453","wikidata":"https://www.wikidata.org/wiki/Q5172842","display_name":"Correlation","level":2,"score":0.30559998750686646},{"id":"https://openalex.org/C58471807","wikidata":"https://www.wikidata.org/wiki/Q327120","display_name":"Receiver operating characteristic","level":2,"score":0.298799991607666},{"id":"https://openalex.org/C28719098","wikidata":"https://www.wikidata.org/wiki/Q44946","display_name":"Point (geometry)","level":2,"score":0.29499998688697815},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.29280000925064087},{"id":"https://openalex.org/C2776502983","wikidata":"https://www.wikidata.org/wiki/Q690182","display_name":"Contrast (vision)","level":2,"score":0.28690001368522644},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.2816999852657318},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.27639999985694885},{"id":"https://openalex.org/C132094186","wikidata":"https://www.wikidata.org/wiki/Q641585","display_name":"Clutter","level":3,"score":0.2759999930858612}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.08.14.744988","doi":"https://doi.org/10.64898/2026.08.14.744988","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.14.744988","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.08.14.744988","doi":"https://doi.org/10.64898/2026.08.14.744988","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.14.744988","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.504800021648407}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":8,"referenced_works":["https://openalex.org/W2906884244","https://openalex.org/W2991283206","https://openalex.org/W4361001523","https://openalex.org/W4416334793","https://openalex.org/W4417454607","https://openalex.org/W7125967877","https://openalex.org/W7165906262","https://openalex.org/W7168382988"],"related_works":["https://openalex.org/W7221670616","https://openalex.org/W3162028695","https://openalex.org/W4408606559","https://openalex.org/W7204942862","https://openalex.org/W2952267545","https://openalex.org/W7165906262","https://openalex.org/W7168382988","https://openalex.org/W4388648559","https://openalex.org/W1998306196","https://openalex.org/W3043574732"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"Sequence-to-function":[2],"models":[3],"predict":[4],"regulatory":[5],"perturbation":[6],"responses,":[7],"but":[8,113],"their":[9],"added":[10],"value":[11,131],"beyond":[12,173],"established":[13],"enhancer-gene":[14],"predictors":[15],"and":[16,26,78,93,103,136,195],"across":[17],"prediction":[18],"tasks":[19],"remains":[20],"unclear.":[21],"We":[22,34],"evaluated":[23],"whole-enhancer":[24,166],"deletion":[25,44,118,167],"sparse":[27,70],"variant":[28,180],"responses":[29,45,72,168,181],"in":[30,95,137],"human":[31],"astrocytes.":[32],"Results":[33],"analyzed":[35],"2,307":[36],"CRISPR-interference-tested":[37],"relations,":[38],"including":[39],"133":[40],"expression-decreasing":[41],"hits.":[42],"Adding":[43],"increased":[46,169],"fully":[47,175],"nested":[48,176],"EGrf":[49],"average":[50,96,110],"precision":[51,111],"from":[52],"0.5475":[53],"to":[54],"0.6137.":[55],"The":[56,145],"paired":[57],"increment":[58],"was":[59],"0.0662":[60],"(enhancer-cluster":[61],"95%":[62,99],"interval":[63],"0.0144-0.1181).":[64],"In":[65,164],"a":[66,174],"separate":[67],"exploratory":[68,158],"analysis,":[69],"Atlas":[71,85,107,122,155],"were":[73,101,157,182,198],"combined":[74],"with":[75],"seven-input":[76],"logistic":[77],"random-forest":[79],"comparators":[80],"by":[81,91],"equal-weight":[82],"rank":[83],"fusion.":[84],"magnitude":[86,108],"fusion":[87,90,123],"exceeded":[88],"absolute-deletion":[89],"0.0519":[92],"0.0637":[94],"precision.":[97],"Enhancer-cluster":[98],"intervals":[100,148],"0.0098-0.0957":[102],"0.0220-0.1094,":[104],"respectively.":[105],"Standalone":[106],"reached":[109],"0.5570,":[112],"its":[114],"advantage":[115],"over":[116],"absolute":[117],"remained":[119,143],"uncertain.":[120,144],"Signed":[121],"performed":[124],"worse":[125],"than":[126,187],"either":[127],"comparator":[128],"alone.":[129],"Incremental":[130],"for":[132],"within-enhancer":[133,192],"target":[134,193],"choice":[135,194],"the":[138,160],"external":[139,196],"WTC11":[140],"MHC":[141],"evaluation":[142],"reported":[146],"performance":[147,172],"use":[149],"one-way":[150],"clustering":[151],"of":[152],"fixed":[153],"predictions;":[154],"analyses":[156],"within":[159],"same":[161],"cohort.":[162],"Conclusions":[163],"AstroREG,":[165],"observed":[170],"retrieval":[171],"chromatin-based":[177],"predictor.":[178],"Sparse":[179],"more":[183],"informative":[184],"as":[185,188],"magnitudes":[186],"signed":[189],"averages.":[190],"Improved":[191],"transfer":[197],"not":[199],"established.":[200]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-08-20T00:00:00"}