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However, a systematic analysis of cell-type\u2013resolved gene regulatory architecture in PD is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we develop an integrative, metacell-based multiscale network analysis (MCMNA) of snRNA-seq data from the substantia nigra to systematically uncover molecular mechanisms and identify potential therapeutic targets for PD. MCMNA overcomes the inherent sparsity of single-cell data by leveraging metacell-based aggregation, enabling construction of robust gene regulatory networks. Gene coexpression network analysis identifies cell-type\u2013specific gene modules associated with PD. Integration of metacell-based differential gene expression and a Bayesian causal network systematically reveals putative driver genes and their hierarchies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our multiscale network models provide a framework for prioritizing candidate molecular regulators and pathways for further investigation of disease mechanisms and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/gigascience\/giag096","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:32:14Z","timestamp":1791286334000},"source":"Crossref","is-referenced-by-count":0,"title":["Multiscale transcriptomic network models of Parkinson\u2019s disease at the single-cell level"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7463-5947","authenticated-orcid":false,"given":"Linh","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]},{"name":"Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York , NY 10029 ,","place":["USA"]},{"name":"Department of Neurology, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]},{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4238-5100","authenticated-orcid":false,"given":"Gefei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]},{"name":"Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York , NY 10029 ,","place":["USA"]},{"name":"Icahn Institute of Genomics, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9350-4467","authenticated-orcid":false,"given":"Xianxiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]},{"name":"Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York , NY 10029 ,","place":["USA"]},{"name":"Icahn Institute of Genomics, Icahn School of Medicine at Mount Sinai , New York, NY 10029 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School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]},{"name":"Friedman Brain Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]},{"name":"Center of Parkinson\u2019s Disease Neurobiology, Icahn School of Medicine at Mount Sinai , New York, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-5653","authenticated-orcid":false,"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]},{"name":"Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York , NY 10029 ,","place":["USA"]},{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]},{"name":"Icahn Institute of Genomics, Icahn 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