{"id":"https://openalex.org/W7213987498","doi":"https://doi.org/10.64898/2026.09.21.752624","title":"SPECTRA: predicting cellular perturbation responses with Graph Learning over Gene Regulatory Networks","display_name":"SPECTRA: predicting cellular perturbation responses with Graph Learning over Gene Regulatory Networks","publication_year":2026,"publication_date":"2026-09-22","ids":{"openalex":"https://openalex.org/W7213987498","doi":"https://doi.org/10.64898/2026.09.21.752624"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.21.752624","doi":"https://doi.org/10.64898/2026.09.21.752624","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.21.752624","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/22/2026.09.21.752624.full.pdf","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://www.biorxiv.org/content/biorxiv/early/2026/09/22/2026.09.21.752624.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5152408744","display_name":"Michele Calabro","orcid":"https://orcid.org/0009-0003-4979-1608","observed_orcids":["https://orcid.org/0009-0003-4979-1608"]},"institutions":[{"id":"https://openalex.org/I4210115812","display_name":"Human Technopole","ror":"https://ror.org/029gmnc79","country_code":"IT","type":"facility","lineage":["https://openalex.org/I4210115812"]},{"id":"https://openalex.org/I93860229","display_name":"Politecnico di Milano","ror":"https://ror.org/01nffqt88","country_code":"IT","type":"education","lineage":["https://openalex.org/I93860229"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Michele Calabr\u00f2","raw_affiliation_strings":["Computational Biology Research Centre, Human Technopole, Milan, Italy","Politecnico di Milano, Milan, Italy"],"raw_orcid":"https://orcid.org/0009-0003-4979-1608","affiliations":[{"raw_affiliation_string":"Computational Biology Research Centre, Human Technopole, Milan, Italy","institution_ids":["https://openalex.org/I4210115812"]},{"raw_affiliation_string":"Politecnico di Milano, Milan, Italy","institution_ids":["https://openalex.org/I93860229"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5152416887","display_name":"Patrick Sheehan","orcid":"https://orcid.org/0009-0004-9071-8530","observed_orcids":["https://orcid.org/0009-0004-9071-8530"]},"institutions":[{"id":"https://openalex.org/I4210115812","display_name":"Human Technopole","ror":"https://ror.org/029gmnc79","country_code":"IT","type":"facility","lineage":["https://openalex.org/I4210115812"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Patrick Sheehan","raw_affiliation_strings":["Computational Biology Research Centre, Human Technopole, Milan, Italy"],"raw_orcid":"https://orcid.org/0009-0004-9071-8530","affiliations":[{"raw_affiliation_string":"Computational Biology Research Centre, Human Technopole, Milan, Italy","institution_ids":["https://openalex.org/I4210115812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066672638","display_name":"Francesco Cambuli","orcid":"https://orcid.org/0000-0002-8753-7729","observed_orcids":["https://orcid.org/0000-0002-8753-7729"]},"institutions":[{"id":"https://openalex.org/I4210115812","display_name":"Human Technopole","ror":"https://ror.org/029gmnc79","country_code":"IT","type":"facility","lineage":["https://openalex.org/I4210115812"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Francesco Cambuli","raw_affiliation_strings":["Computational Biology Research Centre, Human Technopole, Milan, Italy"],"raw_orcid":"https://orcid.org/0000-0002-8753-7729","affiliations":[{"raw_affiliation_string":"Computational Biology Research Centre, Human Technopole, Milan, Italy","institution_ids":["https://openalex.org/I4210115812"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5038260194","display_name":"Andrea Sottoriva","orcid":"https://orcid.org/0000-0001-6709-9533","observed_orcids":["https://orcid.org/0000-0001-6709-9533","https://orcid.org/0000-0003-0645-564X"]},"institutions":[{"id":"https://openalex.org/I4210115812","display_name":"Human Technopole","ror":"https://ror.org/029gmnc79","country_code":"IT","type":"facility","lineage":["https://openalex.org/I4210115812"]}],"countries":["IT"],"is_corresponding":true,"raw_author_name":"Andrea Sottoriva","raw_affiliation_strings":["Computational Biology Research Centre, Human Technopole, Milan, Italy"],"raw_orcid":"https://orcid.org/0000-0001-6709-9533","affiliations":[{"raw_affiliation_string":"Computational Biology Research Centre, Human Technopole, Milan, Italy","institution_ids":["https://openalex.org/I4210115812"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5038260194"],"corresponding_institution_ids":["https://openalex.org/I4210115812"],"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/T10621","display_name":"Gene Regulatory Network Analysis","score":0.8999000191688538,"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/T10621","display_name":"Gene Regulatory Network Analysis","score":0.8999000191688538,"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/T11289","display_name":"Single-cell and spatial transcriptomics","score":0.08150000125169754,"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/T10222","display_name":"Genomics and Chromatin Dynamics","score":0.0031999999191612005,"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/gene-regulatory-networks","display_name":"gene regulatory networks","score":0.9190000295639038},{"id":"https://openalex.org/keywords/graph-neural-networks","display_name":"graph neural networks","score":0.8740000128746033},{"id":"https://openalex.org/keywords/single-cell-transcriptomics","display_name":"single-cell transcriptomics","score":0.8840000033378601},{"id":"https://openalex.org/keywords/variational-autoencoder","display_name":"variational autoencoder","score":0.6610000133514404}],"concepts":[{"id":"https://openalex.org/C66746571","wikidata":"https://www.wikidata.org/wiki/Q1134833","display_name":"ENCODE","level":3,"score":0.7106999754905701},{"id":"https://openalex.org/C67339327","wikidata":"https://www.wikidata.org/wiki/Q1502576","display_name":"Gene regulatory network","level":4,"score":0.6700999736785889},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.6001999974250793},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.5738000273704529},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.5231000185012817},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.5103999972343445},{"id":"https://openalex.org/C177918212","wikidata":"https://www.wikidata.org/wiki/Q803623","display_name":"Perturbation (astronomy)","level":2,"score":0.5044000148773193},{"id":"https://openalex.org/C132525143","wikidata":"https://www.wikidata.org/wiki/Q141488","display_name":"Graph","level":2,"score":0.48820000886917114},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4422000050544739},{"id":"https://openalex.org/C165864922","wikidata":"https://www.wikidata.org/wiki/Q411391","display_name":"Regulation of gene expression","level":3,"score":0.3952000141143799},{"id":"https://openalex.org/C184720557","wikidata":"https://www.wikidata.org/wiki/Q7825049","display_name":"Topology (electrical circuits)","level":2,"score":0.3702000081539154},{"id":"https://openalex.org/C118505674","wikidata":"https://www.wikidata.org/wiki/Q42586063","display_name":"Encoder","level":2,"score":0.3675000071525574},{"id":"https://openalex.org/C21592294","wikidata":"https://www.wikidata.org/wiki/Q3238407","display_name":"Regulatory sequence","level":4,"score":0.35569998621940613},{"id":"https://openalex.org/C152662350","wikidata":"https://www.wikidata.org/wiki/Q815297","display_name":"Systems biology","level":2,"score":0.35510000586509705},{"id":"https://openalex.org/C18431079","wikidata":"https://www.wikidata.org/wiki/Q1502169","display_name":"Gene expression profiling","level":4,"score":0.35260000824928284},{"id":"https://openalex.org/C11413529","wikidata":"https://www.wikidata.org/wiki/Q8366","display_name":"Algorithm","level":1,"score":0.3472999930381775},{"id":"https://openalex.org/C88230418","wikidata":"https://www.wikidata.org/wiki/Q131476","display_name":"Graph theory","level":2,"score":0.3264000117778778},{"id":"https://openalex.org/C199845137","wikidata":"https://www.wikidata.org/wiki/Q145490","display_name":"Network topology","level":2,"score":0.32350000739097595},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.3192000091075897},{"id":"https://openalex.org/C74197172","wikidata":"https://www.wikidata.org/wiki/Q1195339","display_name":"Directed acyclic graph","level":2,"score":0.3001999855041504},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.29580000042915344},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.2903999984264374},{"id":"https://openalex.org/C33498276","wikidata":"https://www.wikidata.org/wiki/Q2138797","display_name":"Regulator gene","level":4,"score":0.2827000021934509},{"id":"https://openalex.org/C80444323","wikidata":"https://www.wikidata.org/wiki/Q2878974","display_name":"Theoretical computer science","level":1,"score":0.28200000524520874},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.2678000032901764},{"id":"https://openalex.org/C169822122","wikidata":"https://www.wikidata.org/wiki/Q230187","display_name":"Crosstalk","level":2,"score":0.2563000023365021},{"id":"https://openalex.org/C146380142","wikidata":"https://www.wikidata.org/wiki/Q1137726","display_name":"Directed graph","level":2,"score":0.25220000743865967}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.21.752624","doi":"https://doi.org/10.64898/2026.09.21.752624","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.21.752624","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/22/2026.09.21.752624.full.pdf","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:10.64898/2026.09.21.752624","doi":"https://doi.org/10.64898/2026.09.21.752624","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.21.752624","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/22/2026.09.21.752624.full.pdf","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":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G2945785948","display_name":null,"funder_award_id":"28961","funder_id":"https://openalex.org/F4320323054","funder_display_name":"Associazione Italiana per la Ricerca sul Cancro"}],"funders":[{"id":"https://openalex.org/F4320323054","display_name":"Associazione Italiana per la Ricerca sul Cancro","ror":"https://ror.org/02g2x7380"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7213987498.pdf","grobid_xml":"https://content.openalex.org/works/W7213987498.grobid-xml"},"referenced_works_count":36,"referenced_works":["https://openalex.org/W1977258127","https://openalex.org/W2056530510","https://openalex.org/W2082979850","https://openalex.org/W2142046859","https://openalex.org/W2150027419","https://openalex.org/W2152951302","https://openalex.org/W2519887557","https://openalex.org/W2554952599","https://openalex.org/W2555109040","https://openalex.org/W2624431344","https://openalex.org/W2734498959","https://openalex.org/W2766453196","https://openalex.org/W2800392236","https://openalex.org/W2937126128","https://openalex.org/W3202649987","https://openalex.org/W4281722965","https://openalex.org/W4377130469","https://openalex.org/W4380742708","https://openalex.org/W4382022265","https://openalex.org/W4385955324","https://openalex.org/W4391262585","https://openalex.org/W4392168151","https://openalex.org/W4403405969","https://openalex.org/W4405166050","https://openalex.org/W4406032773","https://openalex.org/W4408327225","https://openalex.org/W4411690475","https://openalex.org/W4411757935","https://openalex.org/W4411948067","https://openalex.org/W4412929241","https://openalex.org/W4413892920","https://openalex.org/W4416504878","https://openalex.org/W4417297892","https://openalex.org/W7117966374","https://openalex.org/W7158527017","https://openalex.org/W7215048940"],"related_works":["https://openalex.org/W7141691241","https://openalex.org/W6904944501","https://openalex.org/W7117729239","https://openalex.org/W4390340766","https://openalex.org/W4386098065","https://openalex.org/W4415231406","https://openalex.org/W7164826513","https://openalex.org/W7171523608","https://openalex.org/W7169840087","https://openalex.org/W4414737781"],"abstract_inverted_index":{"Abstract":[0],"Predicting":[1],"the":[2,12,22,26,53,151,154,162,195],"transcriptomic":[3,109],"consequences":[4],"of":[5,14,24,29,153,164,197],"cellular":[6,50],"perturbations":[7,75,143],"is":[8,183],"challenging":[9],"due":[10],"to":[11,48,56,188],"sparsity":[13],"single-cell":[15,106,126],"transcriptional":[16,200],"responses,":[17],"heterogeneous":[18],"perturbation":[19,190],"efficiency,":[20],"and":[21,86,99,111,138,192],"difficulty":[23],"identifying":[25],"small":[27],"subset":[28],"genes":[30],"that":[31,72,179],"are":[32,146],"truly":[33],"differentially":[34,130],"expressed":[35,131],"after":[36],"perturbation.":[37],"Current":[38],"approaches":[39],"typically":[40],"encode":[41],"interventions":[42],"as":[43,76],"latent":[44],"shifts":[45],"from":[46],"unperturbed":[47],"perturbed":[49],"state,":[51],"making":[52],"models":[54],"hard":[55],"interpret.":[57],"Here":[58],"we":[59,149],"introduce":[60],"SPEC-TRA":[61],"\u2014":[62,68],"SPEctral":[63],"CRISPR":[64,74],"Transcriptome":[65],"Regulatory":[66,84],"Autoencoder":[67],"a":[69,82,95,100,116,124,165,184],"graph-based":[70,180],"model":[71,155],"treats":[73],"interpretable,":[77],"localized":[78],"signals":[79],"injected":[80],"into":[81,115],"Gene":[83],"Network":[85],"propagated":[87],"through":[88,134],"directed":[89,101],"graph":[90,103],"neural":[91],"networks.":[92],"SPECTRA":[93,122,145],"combines":[94],"variational":[96],"control-cell":[97],"encoder":[98],"heterophilic":[102],"decoder,":[104],"integrating":[105],"expression,":[107],"pretrained":[108],"context,":[110],"prior":[112],"regulatory":[113],"topology":[114],"single":[117],"node-level":[118],"representation.":[119],"We":[120],"evaluate":[121],"on":[123],"large-scale":[125],"CRISPRi":[127],"benchmark,":[128],"measuring":[129],"gene":[132,166],"recovery":[133,196],"precision,":[135],"F1":[136],"score,":[137],"AUPRC-based":[139],"DEG":[140],"classification.":[141],"Since":[142],"in":[144,159],"interpretable":[147],",":[148],"tested":[150],"predictions":[152],"against":[156],"known":[157],"biology,":[158],"cases":[160],"where":[161],"effects":[163],"knock":[167],"out":[168],"have":[169],"been":[170],"repeatedly":[171],"demonstrated":[172],"with":[173],"orthogonal":[174],"experiments.":[175],"Our":[176],"results":[177],"show":[178],"signal":[181],"propagation":[182],"biologically":[185],"grounded":[186],"alternative":[187],"latent-shift":[189],"modeling":[191],"can":[193],"improve":[194],"sparse":[198],"perturbation-induced":[199],"effects.":[201]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-09-22T00:00:00"}