Neuspectrum: A novel transcriptional framework for high-resolution annotation of neutrophil heterogeneity

Neutrophils, long recognized as key players in the innate immune system, play a central role in mediating inflammatory responses and regulatory processes. Recent studies have revealed that neutrophils are heterogeneous and perform distinct functions in the immune system. However, precise identification of peripheral neutrophil subsets remains a significant challenge, as current methodologies fail to completely capture the complexity of neutrophil heterogeneity. To address this challenge, we developed Neuspectrum, an innovative annotation framework that integrates various transcriptional indices to assess the function and maturation state of peripheral neutrophils. Neuspectrum facilitates high-resolution profiling of neutrophil heterogeneity in both single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data and reveals novel heterogeneity within the G5b subset. Furthermore, Neuspectrum predictions provide nuanced insights into changes in peripheral neutrophil heterogeneity, particularly in distinct disease states and during drug interventions. In summary, Neuspectrum serves as a novel tool for assessing neutrophil heterogeneity, thereby providing a powerful platform for identifying neutrophil subsets and developing strategies for neutrophil-associated diseases.