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Traditional methods for analyzing functional calcium imaging data rely heavily on spatial features, such as the compact shapes of somas, to extract regions of interest and their associated temporal traces. This spatial dependency can introduce biases in time trace estimation and limit the applicability of these methods across different neuronal morphologies and imaging scales. To address these limitations, the Graph Filtered Temporal Dictionary Learning (GraFT) uses a graph-based approach to identify neural components based on shared temporal activity rather than spatial proximity, enhancing generalizability across diverse datasets. Here we present significant advancements to the GraFT algorithm, including the integration of a more efficient solver for the L1 least absolute shrinkage and selection operator (LASSO) problem and the application of compressive sensing techniques to reduce computational complexity. By employing random projections to reduce data dimensionality, we achieve substantial speedups while maintaining analytical accuracy. These advancements significantly accelerate the GraFT algorithm, making it more scalable for larger and more complex datasets. Moreover, to increase accessibility, we developed a graphical user interface to facilitate running and analyzing the outputs of GraFT. Finally, we demonstrate the utility of GraFT to imaging data beyond meso-scale imaging, including vascular and axonal imaging.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1014038","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T20:02:01Z","timestamp":1773345721000},"page":"e1014038","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fast and accessible morphology-free functional fluorescence imaging analysis"],"prefix":"10.1371","volume":"22","author":[{"given":"Alejandro","family":"Estrada Berlanga","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabrielle Y.","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Kwok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3733-486X","authenticated-orcid":true,"given":"Thomas","family":"Broggini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Lawlor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kishore V.","family":"Kuchibhotla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Kleinfeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5287-3626","authenticated-orcid":true,"given":"Gal","family":"Mishne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9045-3489","authenticated-orcid":true,"given":"Adam S.","family":"Charles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"issue":"1","key":"pcbi.1014038.ref001","doi-asserted-by":"crossref","first-page":"5165","DOI":"10.1038\/s41467-022-32886-w","article-title":"Fast, efficient, and accurate neuro-imaging denoising via supervised deep learning","volume":"13","author":"S Chaudhary","year":"2022","journal-title":"Nature Communications"},{"issue":"8","key":"pcbi.1014038.ref002","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1507110112","article-title":"Whole-brain calcium imaging with cellular resolution in freely behaving Caenorhabditis elegans","volume":"113","author":"JP Nguyen","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi.1014038.ref003","volume-title":"In vivo optical imaging of brain function","author":"RD Frostig","year":"2010"},{"issue":"3","key":"pcbi.1014038.ref004","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1113\/jphysiol.1971.sp009641","article-title":"Depolarization and calcium entry in squid giant axons","volume":"218","author":"PF Baker","year":"1971","journal-title":"J Physiol"},{"issue":"1","key":"pcbi.1014038.ref005","doi-asserted-by":"crossref","DOI":"10.1101\/pdb.top089367","article-title":"Voltage-sensitive dye imaging of neocortical activity","volume":"2016","author":"A Grinvald","year":"2016","journal-title":"Cold Spring Harbor Protocols"},{"issue":"39","key":"pcbi.1014038.ref006","doi-asserted-by":"crossref","first-page":"14063","DOI":"10.1073\/pnas.0506029102","article-title":"Imaging input and output of neocortical networks in vivo","volume":"102","author":"JND Kerr","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7458","key":"pcbi.1014038.ref007","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nature12354","article-title":"Ultrasensitive fluorescent proteins for imaging neuronal activity","volume":"499","author":"T-W Chen","year":"2013","journal-title":"Nature"},{"issue":"4","key":"pcbi.1014038.ref008","doi-asserted-by":"crossref","first-page":"041402","DOI":"10.1117\/1.NPh.9.4.041402","article-title":"Review of data processing of functional optical microscopy for neuroscience","volume":"9","author":"H Benisty","year":"2022","journal-title":"Neurophotonics"},{"key":"pcbi.1014038.ref009","doi-asserted-by":"crossref","unstructured":"Mishne G, Charles AS. 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