{"id":"https://openalex.org/W7220989158","doi":"https://doi.org/10.48550/arxiv.2610.09643","title":"CircuitATLAS: Agentic reasoning over a systems neuroscience knowledge graph for target discovery in circuitopathies","display_name":"CircuitATLAS: Agentic reasoning over a systems neuroscience knowledge graph for target discovery in circuitopathies","publication_year":2026,"publication_date":"2026-10-07","ids":{"openalex":"https://openalex.org/W7220989158","doi":"https://doi.org/10.48550/arxiv.2610.09643"},"language":"en","primary_location":{"id":"pmh:oai:arXiv.org:2610.09643","doi":null,"is_oa":true,"landing_page_url":"https://arxiv.org/abs/2610.09643","pdf_url":"https://arxiv.org/pdf/2610.09643","source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":"2331-8422","issn":["2331-8422"],"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"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":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"text"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["arxiv","datacite"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://arxiv.org/pdf/2610.09643","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5056516430","display_name":"Gabriel Ocana-Santero","orcid":"https://orcid.org/0000-0001-9270-0589","observed_orcids":["https://orcid.org/0000-0001-9270-0589"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ocana-Santero, Gabriel","raw_affiliation_strings":["Exin Therapeutics, Inc. , 2261 Market Street STE 22614 , San Francisco , California 94114 , United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Exin Therapeutics, Inc. , 2261 Market Street STE 22614 , San Francisco , California 94114 , United States","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5120027845","display_name":"Marko Tvrdic","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Tvrdic, Marko","raw_affiliation_strings":["Exin Therapeutics, Inc. , 2261 Market Street STE 22614 , San Francisco , California 94114 , United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Exin Therapeutics, Inc. , 2261 Market Street STE 22614 , San Francisco , California 94114 , United States","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"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/T10211","display_name":"Computational Drug Discovery Methods","score":0.9336000084877014,"subfield":{"id":"https://openalex.org/subfields/3002","display_name":"Drug Discovery"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9336000084877014,"subfield":{"id":"https://openalex.org/subfields/3002","display_name":"Drug Discovery"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11710","display_name":"Biomedical Text Mining and Ontologies","score":0.025800000876188278,"subfield":{"id":"https://openalex.org/subfields/2718","display_name":"Health Informatics"},"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/T10077","display_name":"Neuroscience and Neuropharmacology Research","score":0.005799999926239252,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/drug-target-identification","display_name":"drug target identification","score":0.6549999713897705},{"id":"https://openalex.org/keywords/agentic-reasoning","display_name":"agentic reasoning","score":0.890999972820282},{"id":"https://openalex.org/keywords/atp1a3","display_name":"ATP1A3","score":0.8980000019073486},{"id":"https://openalex.org/keywords/na-k-atpase","display_name":"Na+/K+-ATPase","score":0.9359999895095825},{"id":"https://openalex.org/keywords/cortical-excitability","display_name":"cortical excitability","score":0.9779999852180481},{"id":"https://openalex.org/keywords/interneurons","display_name":"interneurons","score":0.7919999957084656},{"id":"https://openalex.org/keywords/4-aminopyridine","display_name":"4-aminopyridine","score":0.7570000290870667},{"id":"https://openalex.org/keywords/small-molecule-drug-design","display_name":"small-molecule drug design","score":0.5529999732971191}],"concepts":[{"id":"https://openalex.org/C177212765","wikidata":"https://www.wikidata.org/wiki/Q627335","display_name":"Workflow","level":2,"score":0.6662999987602234},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.6237000226974487},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.6126000285148621},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.5317000150680542},{"id":"https://openalex.org/C132525143","wikidata":"https://www.wikidata.org/wiki/Q141488","display_name":"Graph","level":2,"score":0.48190000653266907},{"id":"https://openalex.org/C118403218","wikidata":"https://www.wikidata.org/wiki/Q43283","display_name":"Biological neural network","level":2,"score":0.39910000562667847},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.3504999876022339},{"id":"https://openalex.org/C2775924081","wikidata":"https://www.wikidata.org/wiki/Q55608371","display_name":"Control (management)","level":2,"score":0.32899999618530273},{"id":"https://openalex.org/C2987255567","wikidata":"https://www.wikidata.org/wiki/Q33002955","display_name":"Knowledge graph","level":2,"score":0.322299987077713},{"id":"https://openalex.org/C88230418","wikidata":"https://www.wikidata.org/wiki/Q131476","display_name":"Graph theory","level":2,"score":0.3179999887943268},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.3091000020503998},{"id":"https://openalex.org/C106937863","wikidata":"https://www.wikidata.org/wiki/Q7236518","display_name":"Power graph analysis","level":3,"score":0.2962999939918518},{"id":"https://openalex.org/C2780196419","wikidata":"https://www.wikidata.org/wiki/Q1762173","display_name":"Nerve net","level":2,"score":0.2946999967098236},{"id":"https://openalex.org/C188147891","wikidata":"https://www.wikidata.org/wiki/Q147638","display_name":"Cognitive science","level":1,"score":0.29350000619888306},{"id":"https://openalex.org/C28719098","wikidata":"https://www.wikidata.org/wiki/Q44946","display_name":"Point (geometry)","level":2,"score":0.2928999960422516},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.28349998593330383},{"id":"https://openalex.org/C15744967","wikidata":"https://www.wikidata.org/wiki/Q9418","display_name":"Psychology","level":0,"score":0.2799000144004822},{"id":"https://openalex.org/C31288803","wikidata":"https://www.wikidata.org/wiki/Q2617516","display_name":"Systems neuroscience","level":5,"score":0.26330000162124634},{"id":"https://openalex.org/C152662350","wikidata":"https://www.wikidata.org/wiki/Q815297","display_name":"Systems biology","level":2,"score":0.26080000400543213},{"id":"https://openalex.org/C169900460","wikidata":"https://www.wikidata.org/wiki/Q2200417","display_name":"Cognition","level":2,"score":0.25189998745918274}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:arXiv.org:2610.09643","doi":null,"is_oa":true,"landing_page_url":"https://arxiv.org/abs/2610.09643","pdf_url":"https://arxiv.org/pdf/2610.09643","source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":"2331-8422","issn":["2331-8422"],"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"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":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"text"},{"id":"doi:10.48550/arxiv.2610.09643","doi":"https://doi.org/10.48550/arxiv.2610.09643","is_oa":true,"landing_page_url":"https://doi.org/10.48550/arxiv.2610.09643","pdf_url":null,"source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":"2331-8422","issn":["2331-8422"],"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"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-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Preprint"}],"best_oa_location":{"id":"pmh:oai:arXiv.org:2610.09643","doi":null,"is_oa":true,"landing_page_url":"https://arxiv.org/abs/2610.09643","pdf_url":"https://arxiv.org/pdf/2610.09643","source":{"id":"https://openalex.org/S4306400194","display_name":"arXiv (Cornell University)","issn_l":"2331-8422","issn":["2331-8422"],"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"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":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"text"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.8371999859809875,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7220989158.pdf","grobid_xml":"https://content.openalex.org/works/W7220989158.grobid-xml"},"referenced_works_count":4,"referenced_works":["https://openalex.org/W3027879771","https://openalex.org/W4403795293","https://openalex.org/W4404941741","https://openalex.org/W4417464290"],"related_works":["https://openalex.org/W4404943793","https://openalex.org/W7133207548","https://openalex.org/W7111968092","https://openalex.org/W4417464290","https://openalex.org/W2960744268","https://openalex.org/W6902146707","https://openalex.org/W7165870978","https://openalex.org/W7172413525","https://openalex.org/W4221048327","https://openalex.org/W7164381641"],"abstract_inverted_index":{"Drug":[0],"discovery":[1,64],"for":[2,62,229],"neurological":[3],"disease":[4,136],"has":[5],"traditionally":[6],"centered":[7],"on":[8,181,235,243],"the":[9,15,23,116,173,189,202,220],"molecules":[10,16],"altered":[11],"by":[12],"disease.":[13],"But":[14],"that":[17,132],"cause":[18],"pathology":[19],"are":[20],"not":[21,233],"necessarily":[22],"best":[24],"points":[25,39],"from":[26,134],"which":[27,34],"to":[28,43,91,144,163,194,218,248],"reverse":[29],"it.":[30],"Here,":[31],"we":[32,153],"ask":[33],"otherwise":[35],"unaltered":[36],"molecular":[37,81,145],"control":[38,179],"can":[40,245],"be":[41,246],"engaged":[42],"restore":[44,249],"pathological":[45],"neural":[46],"circuits":[47],"toward":[48],"functional":[49],"states.":[50],"We":[51,126],"present":[52],"CircuitATLAS,":[53],"a":[54,155,178,195,209,215,227],"provenance-grounded":[55],"systems-neuroscience":[56],"knowledge":[57],"graph":[58,96],"and":[59,80,88,101,110,120,141,149,191,201],"agentic":[60,130],"framework":[61,168,228],"target":[63,204],"in":[65,123,157,199,214,240],"circuitopathies.":[66],"It":[67],"structures":[68],"literature-derived":[69],"relationships":[70],"across":[71],"diseases,":[72],"phenotypes,":[73],"electrophysiology,":[74],"circuits,":[75],"brain":[76],"regions,":[77],"cell":[78],"types":[79],"effectors,":[82],"while":[83],"deliberately":[84],"excluding":[85],"direct":[86],"disease-gene":[87],"disease-protein":[89],"edges":[90],"reduce":[92],"shortcut":[93],"reasoning.":[94],"The":[95],"contains":[97],"3.83":[98],"million":[99,103,107],"nodes":[100],"7.66":[102],"edges,":[104],"including":[105],"5.31":[106],"LLM-extracted":[108],"relations,":[109],"incorporates":[111],"structured":[112],"datasets":[113],"such":[114],"as":[115,177],"Human":[117],"Cell":[118],"Atlas":[119],"new":[121],"multimodal":[122],"vivo":[124,158],"measurements.":[125],"then":[127,206],"introduce":[128,154],"an":[129,169],"workflow":[131],"reasons":[133],"measurable":[135],"phenotypes":[137],"through":[138],"their":[139],"circuit":[140,250],"cellular":[142],"substrates":[143],"interventions,":[146],"therapeutic":[147],"feasibility":[148],"clinical":[150],"constraints.":[151],"Finally,":[152],"human-governed":[156],"lab-in-the-loop":[159],"linking":[160],"hypothesis":[161],"generation":[162],"experimental":[164],"iteration.":[165],"Within":[166],"this":[167],"agent":[170],"nominated":[171],"ATP1A3,":[172],"neuronal":[174],"alpha3":[175],"Na+/K+-ATPase,":[176],"point":[180],"cortical":[182],"excitability;":[183],"interneuron-restricted":[184],"expression":[185],"of":[186,222],"ATP1A3":[187],"abolished":[188],"beta-":[190],"gamma-band":[192],"response":[193],"focal":[196],"4-aminopyridine":[197],"challenge":[198],"vivo,":[200],"validated":[203],"was":[205],"carried":[207],"into":[208],"structure-guided":[210],"small-molecule":[211],"campaign":[212],"terminating":[213],"defined":[216],"assay":[217],"resolve":[219],"direction":[221],"modulation.":[223],"CircuitATLAS":[224],"thus":[225],"provides":[226],"discovering":[230],"therapeutics":[231],"based":[232],"only":[234],"what":[236,244],"is":[237],"molecularly":[238],"disrupted":[239],"disease,":[241],"but":[242],"controlled":[247],"function.":[251]},"counts_by_year":[],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2026-10-09T00:00:00"}
