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DBSOMA: A Machine Learning Method that Identifies Chemical Modulators of Transcriptional States Uncovers Effectors of Beta-Cell Maturation

ABSTRACT: There are currently few high-throughput ways to determine the aptness of applying the transcriptional readout of a biological perturbation to specific systems. Herein we use density analysis of transcriptional correlations to computationally predict whether a given perturbation readout is relevant to Stem Cell derived islet (SC-Islet) maturation. The approach, Denisty Based Self-Organizing Map Analysis (DBSOMA), first learns patterns of gene expression represented in scRNA-seq sets by clustering genes with the Self-Organizing-Map (SOM) algorithm. Perturbation expression profiles and other gene lists are then projected onto the SOM grid, where the degree of clustering is determined by the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm. Filtering based on the degree of structure and the degree of overlap with a desired state yields candidate perturbagens for use in that system. Here we applied DBSOMA to SC-Islet maturation and identified known and novel regulators of β-cell maturation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE309159 | GEO | 2026/01/30

REPOSITORIES: GEO

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Single nuclei multiomics of human stem cell-derived islets identifies deficiencies in lineage specification

Project description:We profiled the transcritpome and ATAC profiles of human pancreatic islets generated from pluripotent stem cells. Multiomic profiling was also performed on primary human islets and in vivo matured SC-islets for comparision. We catalogued the ATAC associated signatures for each cell types in SC-islets and compared them to their human primiary islet counterparts. In vivo maturation of SC-islets were also compared with in vitro SC-islets. In this study, we identified key regulators associated with islet identity during differentiation and maturation. Gene manipulation of CTCF affects differentiating SC-islet cell fate to enteroendocrine-like lineage. ARID1B knockdown caueses islet cells to present mature signatures. These gene altered SC-islets were also sequenced.

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