De novo Gene Signature Identification from Single-Cell RNA-Seq with Hierarchical Poisson Factorization
De novo Gene Signature Identification from Single-Cell RNA-Seq with Hierarchical Poisson Factorization
Abstract Common approaches to gene signature discovery in single cell RNA-sequencing (scRNA-seq) depend upon predefined structures like clusters or pseudo-temporal order, require prior normalization, or do not account for the sparsity of single cell data. We present single cell Hierarchical Poisson Factorization (scHPF), a Bayesian factorization method that adapts Hierarchical Poisson Factorization [1] for de novo discovery of both continuous and discrete expression patterns from scRNA-seq. scHPF does not require prior normalization and captures statistical properties of single cell data better than other methods in benchmark datasets. Applied to scRNA-seq of the core and margin of a high-grade glioma, scHPF uncovers marked differences in the abundance of glioma subpopulations across tumor regions and subtle, regionally-associated expression biases within glioma subpopulations. scHFP revealed an expression signature that was spatially biased towards the glioma-infiltrated margins and associated with inferior survival in glioblastoma.
Levitin Hanna Mendes、Cheng Yim Ling、Bruce Jeffrey N.、Canoll Peter、Blei David M.、Sims Peter A.、Bush Erin C.、Lasorella Anna、Iavarone Antonio、Ruiz Francisco J.R.、Yuan Jinzhou
Department of Systems Biology, Columbia University Medical CenterDepartment of Systems Biology, Columbia University Medical CenterDepartment of Neurological Surgery, Columbia University Medical CenterDepartment of Pathology and Cell Biology, Columbia University Medical CenterDepartment of Computer Science, Columbia University||Department of Statistics, Columbia University Medical CenterDepartment of Systems Biology, Columbia University Medical Center||Sulzberger Columbia Genome Center, Columbia University Medical Center||Department of Biochemistry and Molecular Biophysics, Columbia University Medical CenterDepartment of Systems Biology, Columbia University Medical Center||Sulzberger Columbia Genome Center, Columbia University Medical CenterDepartment of Pathology and Cell Biology, Columbia University Medical Center||Institute for Cancer Genetics, Columbia University Medical Center||Deparment of Pediatrics, Columbia University Medical CenterDepartment of Pathology and Cell Biology, Columbia University Medical Center||Institute for Cancer Genetics, Columbia University Medical Center||Department of Neurology, Columbia University Medical CenterDepartment of Computer Science, Columbia University||Department of Engineering, University of CambridgeDepartment of Systems Biology, Columbia University Medical Center
基础医学生物科学研究方法、生物科学研究技术肿瘤学
Levitin Hanna Mendes,Cheng Yim Ling,Bruce Jeffrey N.,Canoll Peter,Blei David M.,Sims Peter A.,Bush Erin C.,Lasorella Anna,Iavarone Antonio,Ruiz Francisco J.R.,Yuan Jinzhou.De novo Gene Signature Identification from Single-Cell RNA-Seq with Hierarchical Poisson Factorization[EB/OL].(2025-03-28)[2025-05-05].https://www.biorxiv.org/content/10.1101/367003.点此复制
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