{"id":"https://openalex.org/W7223453484","doi":"https://doi.org/10.64898/2026.10.22.761199","title":"Overcoming segmentation bottlenecks in brain tissue for spatial proteomic inference at population scale","display_name":"Overcoming segmentation bottlenecks in brain tissue for spatial proteomic inference at population scale","publication_year":2026,"publication_date":"2026-10-24","ids":{"openalex":"https://openalex.org/W7223453484","doi":"https://doi.org/10.64898/2026.10.22.761199"},"language":"en","primary_location":{"id":"doi:10.64898/2026.10.22.761199","doi":"https://doi.org/10.64898/2026.10.22.761199","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.22.761199","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":"acceptedVersion","is_accepted":true,"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/10.64898/2026.10.22.761199","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5123856121","display_name":"Liang You","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Liang You","raw_affiliation_strings":["Department of Biostatistics and Health Data Science, University of Pittsburgh, Pittsburgh, PA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biostatistics and Health Data Science, University of Pittsburgh, Pittsburgh, PA, USA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5123868798","display_name":"Jamie L. Durbin","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jamie L. Durbin","raw_affiliation_strings":["Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5001850750","display_name":"Guanqun Meng","orcid":"https://orcid.org/0000-0003-2085-9931","observed_orcids":["https://orcid.org/0000-0003-2085-9931"]},"institutions":[{"id":"https://openalex.org/I919571938","display_name":"The University of Texas Health Science Center at Houston","ror":"https://ror.org/03gds6c39","country_code":"US","type":"education","lineage":["https://openalex.org/I919571938"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Guanqun Meng","raw_affiliation_strings":["Department of Biostatistics and Data Science, University of Texas Health Science Center, Houston, TX, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biostatistics and Data Science, University of Texas Health Science Center, Houston, TX, USA","institution_ids":["https://openalex.org/I919571938"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014047965","display_name":"Wayne Stallaert","orcid":"https://orcid.org/0000-0001-8064-6503","observed_orcids":["https://orcid.org/0000-0001-8064-6503"]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wayne Stallaert","raw_affiliation_strings":["Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100406312","display_name":"Guang Li","orcid":"https://orcid.org/0000-0002-8546-2364","observed_orcids":["https://orcid.org/0000-0002-8546-2364"]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Guang Li","raw_affiliation_strings":["Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045609598","display_name":"Shikhar Uttam","orcid":"https://orcid.org/0000-0002-0897-2918","observed_orcids":["https://orcid.org/0000-0002-0897-2918"]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Shikhar Uttam","raw_affiliation_strings":["Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5128830513","display_name":"Hao Feng","orcid":"https://orcid.org/0000-0003-2243-9949","observed_orcids":["https://orcid.org/0000-0003-2243-9949"]},"institutions":[{"id":"https://openalex.org/I919571938","display_name":"The University of Texas Health Science Center at Houston","ror":"https://ror.org/03gds6c39","country_code":"US","type":"education","lineage":["https://openalex.org/I919571938"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hao Feng","raw_affiliation_strings":["Department of Biostatistics and Data Science, University of Texas Health Science Center, Houston, TX, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biostatistics and Data Science, University of Texas Health Science Center, Houston, TX, USA","institution_ids":["https://openalex.org/I919571938"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046410151","display_name":"Jill R. Glausier","orcid":"https://orcid.org/0000-0001-9838-3414","observed_orcids":["https://orcid.org/0000-0001-9838-3414"]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jill R. Glausier","raw_affiliation_strings":["Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5159422026","display_name":"Jiebiao Wang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jiebiao Wang","raw_affiliation_strings":["Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA","Department of Biostatistics and Health Data Science, University of Pittsburgh, Pittsburgh, PA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA","institution_ids":["https://openalex.org/I170201317"]},{"raw_affiliation_string":"Department of Biostatistics and Health Data Science, University of Pittsburgh, Pittsburgh, PA, USA","institution_ids":["https://openalex.org/I170201317"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5159422026"],"corresponding_institution_ids":["https://openalex.org/I170201317"],"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/T12859","display_name":"Cell Image Analysis Techniques","score":0.9218999743461609,"subfield":{"id":"https://openalex.org/subfields/1304","display_name":"Biophysics"},"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/T12859","display_name":"Cell Image Analysis Techniques","score":0.9218999743461609,"subfield":{"id":"https://openalex.org/subfields/1304","display_name":"Biophysics"},"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":0.06790000200271606,"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/T10052","display_name":"Medical Image Segmentation Techniques","score":0.003700000001117587,"subfield":{"id":"https://openalex.org/subfields/1707","display_name":"Computer Vision and Pattern Recognition"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/spatial-proteomics","display_name":"spatial proteomics","score":0.8629999756813049},{"id":"https://openalex.org/keywords/cell-segmentation","display_name":"cell segmentation","score":0.9319999814033508},{"id":"https://openalex.org/keywords/brain-tissue","display_name":"brain tissue","score":0.8100000023841858},{"id":"https://openalex.org/keywords/prefrontal-cortex","display_name":"prefrontal cortex","score":0.9160000085830688},{"id":"https://openalex.org/keywords/foundation-models","display_name":"foundation models","score":0.6729999780654907},{"id":"https://openalex.org/keywords/domain-adaptation","display_name":"domain adaptation","score":0.871999979019165},{"id":"https://openalex.org/keywords/fine-tuning","display_name":"fine-tuning","score":0.6940000057220459},{"id":"https://openalex.org/keywords/alzheimer-s-disease","display_name":"Alzheimer's disease","score":0.7839999794960022},{"id":"https://openalex.org/keywords/neurofibrillary-tangles","display_name":"neurofibrillary tangles","score":0.9350000023841858},{"id":"https://openalex.org/keywords/amyloid-plaques","display_name":"amyloid plaques","score":0.9779999852180481},{"id":"https://openalex.org/keywords/olig2","display_name":"Olig2","score":0.9179999828338623},{"id":"https://openalex.org/keywords/graph-attention-networks","display_name":"graph attention networks","score":0.6259999871253967},{"id":"https://openalex.org/keywords/cell-morphology","display_name":"cell morphology","score":0.5519999861717224},{"id":"https://openalex.org/keywords/immunofluorescence","display_name":"immunofluorescence","score":0.7670000195503235},{"id":"https://openalex.org/keywords/single-nucleus-rna-sequencing","display_name":"single-nucleus RNA sequencing","score":0.7850000262260437},{"id":"https://openalex.org/keywords/spatial-transcriptomics","display_name":"spatial transcriptomics","score":0.796999990940094},{"id":"https://openalex.org/keywords/cell-type-identification","display_name":"cell type annotation","score":0.33000001311302185}],"concepts":[{"id":"https://openalex.org/C89600930","wikidata":"https://www.wikidata.org/wiki/Q1423946","display_name":"Segmentation","level":2,"score":0.7200999855995178},{"id":"https://openalex.org/C46111723","wikidata":"https://www.wikidata.org/wiki/Q471857","display_name":"Proteomics","level":3,"score":0.6122999787330627},{"id":"https://openalex.org/C2776214188","wikidata":"https://www.wikidata.org/wiki/Q408386","display_name":"Inference","level":2,"score":0.6103000044822693},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.5842000246047974},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.557200014591217},{"id":"https://openalex.org/C43521106","wikidata":"https://www.wikidata.org/wiki/Q2165493","display_name":"Pipeline (software)","level":2,"score":0.515500009059906},{"id":"https://openalex.org/C153180895","wikidata":"https://www.wikidata.org/wiki/Q7148389","display_name":"Pattern recognition (psychology)","level":2,"score":0.489300012588501},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.4876999855041504},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.37770000100135803},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.367900013923645},{"id":"https://openalex.org/C124504099","wikidata":"https://www.wikidata.org/wiki/Q56933","display_name":"Image segmentation","level":3,"score":0.3181999921798706},{"id":"https://openalex.org/C2777670902","wikidata":"https://www.wikidata.org/wiki/Q492038","display_name":"Human brain","level":2,"score":0.3163999915122986},{"id":"https://openalex.org/C177212765","wikidata":"https://www.wikidata.org/wiki/Q627335","display_name":"Workflow","level":2,"score":0.31310001015663147},{"id":"https://openalex.org/C159620131","wikidata":"https://www.wikidata.org/wiki/Q1938983","display_name":"Spatial analysis","level":2,"score":0.3068999946117401},{"id":"https://openalex.org/C86251818","wikidata":"https://www.wikidata.org/wiki/Q816754","display_name":"Benchmarking","level":2,"score":0.3009999990463257},{"id":"https://openalex.org/C2776434776","wikidata":"https://www.wikidata.org/wiki/Q19246213","display_name":"Domain adaptation","level":3,"score":0.2678999900817871},{"id":"https://openalex.org/C2780972224","wikidata":"https://www.wikidata.org/wiki/Q17047956","display_name":"Brain atlas","level":2,"score":0.2590999901294708}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.64898/2026.10.22.761199","doi":"https://doi.org/10.64898/2026.10.22.761199","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.22.761199","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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},{"id":"pmh:oai:pubmedcentral.nih.gov:13738775","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13738775/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"bioRxiv","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.64898/2026.10.22.761199","doi":"https://doi.org/10.64898/2026.10.22.761199","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.22.761199","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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.46810001134872437,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":39,"referenced_works":["https://openalex.org/W2035084050","https://openalex.org/W2107018762","https://openalex.org/W2114104545","https://openalex.org/W2136068915","https://openalex.org/W2295598076","https://openalex.org/W2466314544","https://openalex.org/W2786358356","https://openalex.org/W2793877399","https://openalex.org/W2806530968","https://openalex.org/W2809330972","https://openalex.org/W2942678593","https://openalex.org/W2946901414","https://openalex.org/W2980998394","https://openalex.org/W3044030235","https://openalex.org/W3058283092","https://openalex.org/W3082377112","https://openalex.org/W3111521801","https://openalex.org/W3129476455","https://openalex.org/W3164786883","https://openalex.org/W3185312825","https://openalex.org/W3196897371","https://openalex.org/W3205339884","https://openalex.org/W3214596602","https://openalex.org/W4210853280","https://openalex.org/W4220765701","https://openalex.org/W4283704002","https://openalex.org/W4306411710","https://openalex.org/W4308361273","https://openalex.org/W4312128822","https://openalex.org/W4322774807","https://openalex.org/W4385302628","https://openalex.org/W4400948944","https://openalex.org/W4402340839","https://openalex.org/W4402706179","https://openalex.org/W4406931967","https://openalex.org/W4409988818","https://openalex.org/W4410858661","https://openalex.org/W4410894786","https://openalex.org/W4413381933"],"related_works":["https://openalex.org/W7149008056","https://openalex.org/W6912081689","https://openalex.org/W4416072332","https://openalex.org/W7081659162","https://openalex.org/W7220429962","https://openalex.org/W4404048056","https://openalex.org/W7160765622","https://openalex.org/W4308361273","https://openalex.org/W4414349981","https://openalex.org/W4406061222"],"abstract_inverted_index":{"Abstract":[0],"In":[1],"spatial":[2,50,101,188],"proteomics":[3,189],"across":[4],"large":[5],"cohorts,":[6],"downstream":[7,39],"estimates":[8],"from":[9,60,87,106],"tens":[10],"of":[11,13,64],"thousands":[12],"images":[14,63,105],"depend":[15],"on":[16],"accurate":[17],"cell":[18,28,58,84,93,157,167],"segmentation.":[19],"Yet":[20],"pretrained":[21],"segmentation":[22,72,85],"models":[23,114,179],"struggle":[24],"with":[25,96],"morphologically":[26],"complex":[27,182],"bodies":[29,59],"in":[30,187],"human":[31,66],"brain":[32],"tissue,":[33],"and":[34,77,91,100,141,162],"how":[35],"domain":[36],"adaptation":[37],"affects":[38],"discovery":[40,121,186],"remains":[41],"unclear.":[42],"Here,":[43],"we":[44,80],"introduce":[45],"SPInfer,":[46],"a":[47,148,174],"workflow":[48],"for":[49,176],"proteomic":[51],"inference":[52],"developed":[53],"using":[54,124,129],"5,832":[55],"manually":[56],"annotated":[57],"120":[61],"immunofluorescence":[62],"the":[65,145,191],"prefrontal":[67],"cortex.":[68],"After":[69],"benchmarking":[70],"eight":[71],"methods":[73],"spanning":[74],"classical,":[75],"convolutional,":[76],"foundation":[78,178],"models,":[79],"adapted":[81],"Cellpose-SAM,":[82],"raising":[83],"F1":[86],"0.37":[88],"to":[89,137,169,180],"0.84":[90],"recovering":[92],"compositions":[94],"concordant":[95],"matched":[97],"single-nucleus":[98],"RNA-seq":[99],"transcriptomics.":[102],"Across":[103],"14,765":[104],"69":[107],"postmortem":[108],"donors,":[109],"identical":[110],"Alzheimer\u2019s":[111],"disease":[112],"pathology":[113],"found":[115],"no":[116],"significant":[117],"associations":[118],"after":[119],"false":[120],"rate":[122],"correction":[123],"zero-shot":[125],"masks,":[126,147],"versus":[127],"four":[128,156],"fine-tuned":[130,146],"masks;":[131],"three":[132],"linked":[133,166],"higher":[134],"OLIG2-positive":[135],"fractions":[136],"greater":[138],"neurofibrillary":[139],"tangle":[140],"plaque":[142],"burden.":[143],"Using":[144],"graph":[149],"attention":[150],"network":[151],"over":[152],"nuclear":[153],"neighborhoods":[154],"classified":[155],"types":[158],"without":[159],"marker":[160],"information,":[161],"differential":[163],"expression":[164],"analysis":[165],"morphology":[168],"gene":[170],"expression.":[171],"This":[172],"provides":[173],"pipeline":[175],"fine-tuning":[177],"segment":[181],"tissues,":[183],"enabling":[184],"biological":[185],"at":[190],"population":[192],"scale.":[193]},"counts_by_year":[],"updated_date":"2026-11-08T12:12:28.789561","created_date":"2026-10-25T00:00:00"}
