{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:00:44Z","timestamp":1785276044322,"version":"3.55.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":180,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ELIXIR Italy"},{"name":"Italian node of ELIXIR Europe"},{"name":"European distributed research infrastructure for life-science data"},{"name":"Piano Nazionale di Ripresa e Resilienza","award":["B53C24002140004"],"award-info":[{"award-number":["B53C24002140004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Single-cell RNA sequencing enables high-resolution characterization of transcriptional heterogeneity, but provides only a partial view of the regulatory and metabolic processes associated with cellular states. Several computational methods infer transcription factor (TF) activity and metabolic features directly from RNA, yielding complementary functional representations of cellular organisation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we use a latent factor organisational strategy to jointly model four transcriptome-derived functional projections, namely gene expression, TF regulon activity, metabolite-level features and predicted metabolic fluxes. Although all layers originate from the same measurement, each captures distinct regulatory or metabolic programs. The resulting latent space organizes these inferred programs into coordinated axes of variation guided by complementary regulatory and metabolic constraints, facilitating functional interpretation beyond gene expression alone. When applied to a breast cancer cell line dataset, the proposed framework identifies distinct functional programs, including proliferative, oxidative-metabolic and stress-associated axes, that are only partially resolved in RNA-only analyses of this dataset. Overall, our results suggest that regulatory and metabolic programs inferred from scRNA-seq can be structured into an interpretable latent representation, supporting a more coherent functional characterization of cellular states from transcriptome-derived functional projections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioadv\/vbag185","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:35:12Z","timestamp":1782822912000},"source":"Crossref","is-referenced-by-count":0,"title":["A latent factor framework to organize regulatory and metabolic programs inferred from scRNA-seq"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7750-5412","authenticated-orcid":false,"given":"Chiara","family":"Napoli","sequence":"first","affiliation":[{"name":"NeuroneLab\u2014Department of Management and Innovation Systems (DISA-MIS), University of Salerno , Fisciano, SA 84084,","place":["Italy"]},{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, Sapienza University of Rome , Rome, RM 00185,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0199-6623","authenticated-orcid":false,"given":"Francesco","family":"Bardozzo","sequence":"additional","affiliation":[{"name":"NeuroneLab\u2014Department of Management and Innovation Systems (DISA-MIS), University of Salerno , Fisciano, SA 84084,","place":["Italy"]},{"name":"NAIR Center (Navarra Artificial Intelligence Research Centre), Calle del Sadar , Pamplona, 31006,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suraj","family":"Verma","sequence":"additional","affiliation":[{"name":"School of Computing, Engineering and Digital Technologies, Teesside University , Middlesbrough, TS1 3BX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9656-7287","authenticated-orcid":false,"given":"Le Minh Thao","family":"Doan","sequence":"additional","affiliation":[{"name":"School of Computing, Engineering and Digital Technologies, Teesside University , Middlesbrough, TS1 3BX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7543-2073","authenticated-orcid":false,"given":"Pierpaolo","family":"Fiore","sequence":"additional","affiliation":[{"name":"NeuroneLab\u2014Department of Management and Innovation Systems (DISA-MIS), University of Salerno , Fisciano, SA 84084,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Faggiano","sequence":"additional","affiliation":[{"name":"NeuroneLab\u2014Department of Management and Innovation Systems (DISA-MIS), University of Salerno , Fisciano, SA 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