{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T17:36:21Z","timestamp":1769448981987,"version":"3.49.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neuroinform."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The accumulation of genomic and brain data opens new opportunities for resource friendly, data driven brain exploration. A key challenge is to develop versatile and accessible strategies that integrate and mine multimodal datasets for novel neuroscientific insights. Here, we optimized an integrated workflow for mapping multigenic evolutionary traits in the human brain across cognitive, cellular, and molecular levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>At the input stage, the workflow fuses an evolutionary genetic dataset with searchable synthetic functional magnetic resonance imaging (fMRI) databases that are pre clustered into concise psychological domains for improved interpretability. At its core, a Genetic Algorithm for Generalized Biclustering (GABi) mines gene sets under evolutionary selection that also show high expression correlation with fMRI networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Applying this workflow, we identified evolutionary patterns spanning cognitive traits, brain cell types, and molecular mechanisms. Focusing on socio affective traits, the algorithm highlighted peaks in adaptive selection in networks for social interaction (language) and social concepts (theory of mind) across hominid, early hominin, and anatomically modern human (AMH) ancestry. These traits emerge from a broad spectrum of excitatory (glutamatergic) and inhibitory (GABAergic) neuronal, as well as non neuronal, cell types. The associated Gene Ontology (GO) terms were enriched for cell signaling, synaptic organization, and neuronal morphology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Together, these findings demonstrate an integrated workflow for molecular to systems level exploration of the brain and provide new perspectives on the evolutionary history of human socio affective functions. This approach can be adapted to screen for functional traits in the context of mental disorders or applied to the brains of other phylogenies in a similar manner.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fninf.2025.1623174","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T07:19:47Z","timestamp":1769411987000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational reconstruction of evolutionary selection in human brain networks"],"prefix":"10.3389","volume":"19","author":[{"given":"Lukasz","family":"Piszczek","sequence":"first","affiliation":[{"name":"Department of Neuronal Cell Biology, Center for Brain Research, Medical University of Vienna","place":["Vienna, Austria"]}]},{"given":"Clara","family":"Fazzari","sequence":"additional","affiliation":[{"name":"Department of Neuronal Cell Biology, Center for Brain Research, Medical University of Vienna","place":["Vienna, Austria"]},{"name":"Department of Biology, University of Rome Tor Vergata","place":["Rome, Italy"]}]},{"given":"Sophia","family":"Ulonska","sequence":"additional","affiliation":[{"name":"Biomedical Image Informatics, VRVis GmbH","place":["Vienna, Austria"]}]},{"given":"Katja","family":"B\u00fchler","sequence":"additional","affiliation":[{"name":"Biomedical Image Informatics, VRVis GmbH","place":["Vienna, Austria"]}]},{"given":"Wulf","family":"Haubensak","sequence":"additional","affiliation":[{"name":"Department of Neuronal Cell Biology, Center for Brain Research, Medical University of Vienna","place":["Vienna, Austria"]},{"name":"Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)","place":["Vienna, Austria"]}]}],"member":"1965","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/1756-6606-4-21","article-title":"Transcriptional dysregulation of 5-HT1A autoreceptors in mental illness","volume":"4","author":"Albert","year":"2011","journal-title":"Mol. Brain"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"513","DOI":"10.3390\/nu14030513","article-title":"The implication of physiological ketosis on the cognitive brain: a narrative review","volume":"14","author":"Altayyar","year":"2022","journal-title":"Nutrients"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/s41593-025-01904-7","article-title":"Integrating multimodal data to understand cortical circuit architecture and function","volume":"28","author":"Arkhipov","year":"2025","journal-title":"Nat. Neurosci."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"5369","DOI":"10.1038\/s41467-021-25680-7","article-title":"Unified AI framework to uncover deep interrelationships between gene expression and Alzheimer\u2019s disease neuropathologies","volume":"12","author":"Beebe-Wang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref9001","doi-asserted-by":"crossref","first-page":"eabq4964","DOI":"10.1126\/science.abq4964","article-title":"The dawn of spatial omics","volume":"381","author":"Bressan","year":"2023","journal-title":"Science"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"824069","DOI":"10.3389\/fnins.2022.824069","article-title":"Imaging genetic based mediation analysis for human cognition","volume":"16","author":"Chen","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref8","first-page":"93","article-title":"Biclustering of expression data","volume":"8","author":"Cheng","year":"2000","journal-title":"Proc Int Conf Intell Syst Mol Biol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1038\/s41559-019-0996-x","article-title":"Inferred divergent gene regulation in archaic hominins reveals potential phenotypic differences","volume":"3","author":"Colbran","year":"2019","journal-title":"Nat Ecol Evol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1186\/s12859-014-0355-5","article-title":"A framework for generalized subspace pattern mining in high-dimensional datasets","volume":"15","author":"Curry","year":"2014","journal-title":"BMC Bioinformatics"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1038\/s41593-024-01624-4","article-title":"Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia","volume":"27","author":"Dear","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1016\/j.cell.2004.11.040","article-title":"Accelerated evolution of nervous system genes in the origin of Homo sapiens","volume":"119","author":"Dorus","year":"2004","journal-title":"Cell"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.2174\/092986707781368450","article-title":"HTR2A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies","volume":"14","author":"Drago","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1016\/j.cell.2009.03.041","article-title":"A humanized version of Foxp2 affects Cortico-basal ganglia circuits in mice","volume":"137","author":"Enard","year":"2009","journal-title":"Cell"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"a021717","DOI":"10.1101\/cshperspect.a021717","article-title":"The origins and Organization of Vertebrate Pavlovian Conditioning","volume":"8","author":"Fanselow","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1126\/science.aaa1975","article-title":"Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion","volume":"347","author":"Florio","year":"2015","journal-title":"Science"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s12110-016-9275-6","article-title":"The driving forces of cultural complexity","volume":"28","author":"Fogarty","year":"2017","journal-title":"Hum. Nat."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.tics.2018.10.005","article-title":"Bridging the gap between connectome and transcriptome","volume":"23","author":"Fornito","year":"2019","journal-title":"Trends Cogn. Sci."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.neuroimage.2017.08.070","article-title":"Predicting functional neuroanatomical maps from fusing brain networks with genetic information","volume":"170","author":"Ganglberger","year":"2018","journal-title":"NeuroImage"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1126\/science.1188021","article-title":"A draft sequence of the Neandertal genome","volume":"328","author":"Green","year":"2010","journal-title":"Science"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1038\/s41562-021-01082-z","article-title":"Mapping gene transcription and neurocognition across human neocortex","volume":"5","author":"Hansen","year":"2021","journal-title":"Nat. Hum. Behav."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1038\/s41593-022-01186-3","article-title":"Mapping neurotransmitter systems to the structural and functional organization of the human neocortex","volume":"25","author":"Hansen","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","article-title":"Array programming with NumPy","volume":"585","author":"Harris","year":"2020","journal-title":"Nature"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/nature11405","article-title":"An anatomically comprehensive atlas of the adult human brain transcriptome","volume":"489","author":"Hawrylycz","year":"2012","journal-title":"Nature"},{"key":"ref9002","first-page":"65","article-title":"A Beginners Guide to Estimating the Non-synonymous to Synonymous Rate Ratio of all Protein-Coding Genes in a Genome. In Parasite Genomics Protocols, Peacock C (ed) New York, NY: Springer New York","author":"Jeffares","year":"2015"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"111287","DOI":"10.1016\/j.celrep.2022.111287","article-title":"Molecular archaeology of human cognitive traits","volume":"40","author":"Kaczanowska","year":"2022","journal-title":"Cell Rep."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1007\/s13258-023-01393-7","article-title":"Association between genetic polymorphisms of synaptophysin (SYP) gene and attention deficit hyperactivity disorder in Korean subjects","volume":"45","author":"Kim","year":"2023","journal-title":"Genes Genomics"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"6296","DOI":"10.1038\/s41598-018-24331-0","article-title":"Reconstructing the Neanderthal brain using computational anatomy","volume":"8","author":"Kochiyama","year":"2018","journal-title":"Sci. Rep."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"5266","DOI":"10.1002\/hbm.26001","article-title":"Regional gene expression patterns are associated with task-specific brain activation during reward and emotion processing measured with functional MRI","volume":"43","author":"Komorowski","year":"2022","journal-title":"Hum. Brain Mapp."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/nbt.4038","article-title":"Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain","volume":"36","author":"Lake","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"8536","DOI":"10.1038\/s41467-025-64259-4","article-title":"Data-driven fine-grained region discovery in the mouse brain with transformers","volume":"16","author":"Lee","year":"2025","journal-title":"Nat. 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Methods"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s42003-025-07505-1","article-title":"Cortical areas associated to higher cognition drove primate brain evolution","volume":"8","author":"Melchionna","year":"2025","journal-title":"Commun Biol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/nature12788","article-title":"A mitochondrial genome sequence of a hominin from Sima de los Huesos","volume":"505","author":"Meyer","year":"2014","journal-title":"Nature"},{"key":"ref36","volume-title":"Nilearn","author":"Chamma","year":"2025"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s13353-011-0069-6","article-title":"Genetic determinants of aggression and impulsivity in humans","volume":"53","author":"Pavlov","year":"2012","journal-title":"J. Appl. Genet."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s41576-023-00643-4","article-title":"More than a decade of genetic research on the Denisovans","volume":"25","author":"Peyr\u00e9gne","year":"2024","journal-title":"Nat. Rev. Genet."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"9704","DOI":"10.1073\/pnas.1903589116","article-title":"Tinbergen\u2019s challenge for the neuroscience of behavior","volume":"116","author":"Pfaff","year":"2019","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"eabl6422","DOI":"10.1126\/science.abl6422","article-title":"Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals","volume":"377","author":"Pinson","year":"2022","journal-title":"Science"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1515\/hsz-2023-0199","article-title":"Towards correlative archaeology of the human mind","volume":"405","author":"Piszczek","year":"2023","journal-title":"Biol. Chem."},{"key":"ref42","article-title":"GRIN1-related neurodevelopmental disorder","volume-title":"GeneReviews\u00ae","author":"Platzer","year":"1993"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/s41576-022-00568-4","article-title":"Human-specific genetics: new tools to explore the molecular and cellular basis of human evolution","volume":"24","author":"Pollen","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"ref44","volume-title":"Figtree","author":"Rambaut","year":"2018"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"R970","DOI":"10.1016\/j.cub.2022.08.027","article-title":"The contribution of Neanderthal introgression to modern human traits","volume":"32","author":"Reilly","year":"2022","journal-title":"Curr. Biol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1126\/science.1255905","article-title":"Correlated gene expression supports synchronous activity in brain networks","volume":"348","author":"Richiardi","year":"2015","journal-title":"Science"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e2218308120","DOI":"10.1073\/pnas.2218308120","article-title":"Large-scale functional screen identifies genetic variants with splicing effects in modern and archaic humans","volume":"120","author":"Rong","year":"2023","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.52294\/001c.87681","article-title":"NiMARE: neuroimaging meta-analysis research environment","volume":"3","author":"Salo","year":"2023","journal-title":"Aperture Neuro"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41587-025-02857-9","article-title":"Multimodal learning enables chat-based exploration of single-cell data","author":"Schaefer","year":"2025","journal-title":"Nat. Biotechnol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"2252","DOI":"10.1038\/s41467-023-37574-x","article-title":"Evolution of cortical geometry and its link to function, behaviour and ecology","volume":"14","author":"Schwartz","year":"2023","journal-title":"Nat. Commun."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"eadd7046","DOI":"10.1126\/science.add7046","article-title":"Transcriptomic diversity of cell types across the adult human brain","volume":"382","author":"Siletti","year":"2023","journal-title":"Science"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1146\/annurev-genom-083117-021749","article-title":"Ancient genomics of modern humans: the first decade","volume":"19","author":"Skoglund","year":"2018","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.gde.2014.09.001","article-title":"Transcriptomic insights into human brain evolution: acceleration, neutrality, heterochrony","volume":"29","author":"Somel","year":"2014","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nature04072","article-title":"Initial sequence of the chimpanzee genome and comparison with the human genome","volume":"437","year":"2005","journal-title":"Nature"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1093\/gbe\/evt017","article-title":"Improving genome-wide scans of positive selection by using protein isoforms of similar length","volume":"5","author":"Villanueva-Ca\u00f1as","year":"2013","journal-title":"Genome Biol. Evol."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: fundamental algorithms for scientific computing in Python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat. Methods"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.nicl.2016.03.015","article-title":"Validity and reliability of four language mapping paradigms","volume":"16","author":"Wilson","year":"2017","journal-title":"NeuroImage Clin"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1093\/oxfordjournals.molbev.a025957","article-title":"Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution","volume":"15","author":"Yang","year":"1998","journal-title":"Mol. Biol. Evol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1093\/molbev\/msm088","article-title":"PAML 4: phylogenetic analysis by maximum likelihood","volume":"24","author":"Yang","year":"2007","journal-title":"Mol. Biol. Evol."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/s41467-024-55611-1","article-title":"Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity","volume":"16","author":"Yao","year":"2025","journal-title":"Nat. Commun."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/nmeth.1635","article-title":"Large-scale automated synthesis of human functional neuroimaging data","volume":"8","author":"Yarkoni","year":"2011","journal-title":"Nat. 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