What makes a pancreatic beta cell different from a delta or an alpha cell? A team from the Endocrine Regulatory Genomics at the Department of Medicine and Life Sciences of Pompeu Fabra University (MELIS-UPF) has developed SPICEY, a computational tool that helps identify which genes and which DNA regulatory regions are specific to each cell type. Applied to pancreatic islets, it may help us better understand how this tissue works in health and diabetes.
Single-cell technologies have revolutionised the way complex tissues such as the pancreas are studied. Instead of analysing a whole tissue as a single average, single-cell technology makes it possible to analyse the genetic material of cells one by one and see more clearly how they differ. But having more data does not always mean understanding it better: there was still no clear way to measure to what extent a gene, or a DNA regulatory region, is truly specific to a particular cell type.
This is where SPICEY comes in. On the one hand, the tool analyses which genes are especially active in each cell population and, on the other, which chromatin regions (the genetic material packed inside the nucleus) are more accessible and may act as “switches” for those genes. Its added value is that it integrates both layers of information.
From known markers to new candidates
Applied to human pancreatic islets, SPICEY recovers known markers of different cell populations, such as insulin in pancreatic beta cells or somatostatin in delta cells. But it also makes it possible to identify new candidates with high cell-type specificity, such as ADCYAP1 in beta cells, which shows a high degree of agreement between expression and chromatin accessibility. This helps connect regulatory regions to their target genes, as well as reconstruct functional relationships within tissue-specific gene regulatory networks.
“SPICEY was developed to fill an important gap in single-cell data analysis: until now, we did not have a clear and quantitative way to measure how specific a gene’s expression or a regulatory element’s activity is to one cell type compared with others”
Georgina Fuentes-Páez, PhD student and one of the lead authors of the study.
This is especially relevant in the case of the pancreas, because many genetic variants associated with diabetes are found in non-coding regions of the genome. In other words, they do not directly alter a gene, but rather its regulation. That is why tools such as SPICEY may be useful for better understanding which regulatory mechanisms matter in health and disease.
Beyond the pancreas and diabetes
Although the study focuses on pancreatic islets, the authors explain that SPICEY is a versatile tool that can be applied to other biological contexts. It may be useful in studies of healthy or diseased tissue, inflammation, treatment response or cell differentiation processes, whenever gene expression and/or regulatory activity data are available across different cell types.
The tool may help prioritise genes and regulatory elements with potential functional relevance for future studies. At a time when biology is generating ever more detailed data, tools such as SPICEY are a reminder that the challenge is not only to obtain information, but also to know how to interpret it.
Fuentes-Páez, G., Molina, N., Ramos-Rodríguez, M. et al. SPICEY: an R package for quantifying tissue specificity from single cell multi-omics data. BMC Bioinformatics 27, 80 (2026).
