scSelector: A Flexible Single-Cell Data Analysis Assistant for Biomedical Researchers

TL;DR

scSelector is a new software tool that helps researchers analyze single-cell RNA sequencing data more flexibly and accurately by combining interactive selection with AI assistance.

Contribution

scSelector introduces an interactive, AI-assisted platform for flexible cell population selection and analysis in scRNA-seq data.

Findings

scSelector identified distinct alpha-cell subpopulations with unique remodeling capabilities in pancreatic tissue.

The tool successfully characterized rare cell populations like platelets in PBMCs and endothelial cells in liver tissue.

Cells discarded by standard QC were found to represent biologically functional subpopulations using scSelector.

Abstract

Background: Standard single-cell RNA sequencing (scRNA-seq) analysis workflows face significant limitations, particularly the rigidity of clustering-dependent methods that can obscure subtle cellular heterogeneity and the potential loss of biologically meaningful cells during stringent quality control (QC) filtering. This study aims to develop scSelector (v1.0), an interactive software toolkit designed to empower researchers to flexibly select and analyze cell populations directly from low-dimensional embeddings, guided by their expert biological knowledge. Methods: scSelector was developed using Python, relying on core dependencies such as Scanpy (v1.9.0), Matplotlib (v3.4.0), and NumPy (v1.20.0). It integrates an intuitive lasso selection tool with backend analytical modules for differential expression and functional enrichment analysis. Furthermore, it incorporates Large Language Model (LLM) assistance via API integration (DeepSeek/Gemini) to provide automated, contextually informed cell-type and state prediction reports. Results: Validation across multiple public datasets demonstrated that scSelector effectively resolves functional heterogeneity within broader cell types, such as identifying distinct alpha-cell subpopulations with unique remodeling capabilities in pancreatic tissue. It successfully characterized rare populations, including platelets in PBMCs and extremely low-abundance endothelial cells in liver tissue (as few as 53 cells). Additionally, scSelector revealed that cells discarded by standard QC can represent biologically functional subpopulations, and it accurately dissected the states of outlier cells, such as proliferative NK cells. Conclusions: scSelector provides a flexible, researcher-centric platform that moves beyond the constraints of automated pipelines. By combining interactive selection with AI-assisted interpretation, it enhances the precision of scRNA-seq analysis and facilitates the discovery of novel cell types and complex cellular behaviors.

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