biostudies-literatureBerson ENIA NIH HHSNCRR NIH HHSNancy and Buster Alvord EndowmentNHLBI NIH HHSNational Institutes of HealthNIGMS NIH HHS13849https://www.ebi.ac.uk/biostudies/studies/S-EPMC10449792biostudies-literatureUnknown13(1)Comparing brain structure across species and regions enables key functional insights. Leveraging publicly available data from a novel mass cytometry-based method, synaptometry by time of flight (SynTOF), we applied an unsupervised machine learning approach to conduct a comparative study of presynapse molecular abundance across three species and three brain regions. We used neural networks and their attractive properties to model complex relationships among high dimensional data to develop a unified, unsupervised framework for comparing the profile of more than 4.5 million single presynapses among normal human, macaque, and mouse samples. An extensive validation showed the feasibility of performing cross-species comparison using SynTOF profiling. Integrative analysis of the abundance of 20 Scientific reportsCross-species comparative analysis of single presynapses.PMC10449792HL122393U19 AG066567AG057915R01 HL122393AG058829UF1 AG057707R01 AG057915AG049638AG068279R01 AG056287HL087103P30 AG066509RF1 AG077443R01 AG068279P30 AG049638RF1 AG058829GM138353R01 HL087103P30 AG072947S10 RR027431R35 GM138353Bendall SCPostupna NBecker MCraft SGajera CRDe Francesco DAghaeepour NChang ALRegister TCMontine KSFox EJRavindra NGPhongpreecha TPerna AShively CALatimer CSEspinosa CBerson EKeene CDBukhari SAMontine TJfalseCross-species comparative analysis of single presynapses.Comparing brain structure across species and regions enables key functional insights. Leveraging publicly available data from a novel mass cytometry-based method, synaptometry by time of flight (SynTOF), we applied an unsupervised machine learning approach to conduct a comparative study of presynapse molecular abundance across three species and three brain regions. We used neural networks and their attractive properties to model complex relationships among high dimensional data to develop a unified, unsupervised framework for comparing the profile of more than 4.5 million single presynapses among normal human, macaque, and mouse samples. An extensive validation showed the feasibility of performing cross-species comparison using SynTOF profiling. Integrative analysis of the abundance of 20 2023-01-01T00:00:00Z2023 Aug2025-05-29T21:44:38.65Z2024-11-08T22:52:41.04ZS-EPMC104497923762036310.1038/s41598-023-40683-8