DOGMA: Weaving Structural Information into Data-centric Single-cell Transcriptomics Analysis

TL;DR

DOGMA introduces a biologically informed, multi-level prior knowledge framework for single-cell transcriptomics, improving data representation, robustness, and efficiency over existing heuristic methods.

Contribution

It presents a novel prior-guided graph construction approach that incorporates biological ontologies for enhanced analysis of single-cell data.

Findings

DOGMA achieves superior zero-shot cell-type classification accuracy.

It uses less GPU memory and inference time compared to baseline methods.

The framework demonstrates robustness across multi-species and multi-organ datasets.

Abstract

Recently, data-centric AI methodology has been a dominant paradigm in single-cell transcriptomics analysis, which treats data representation rather than model complexity as the fundamental bottleneck. In the review of current studies, earlier sequence methods treat cells as independent entities and adapt prevalent ML models to analyze their directly inherited sequence data. Despite their simplicity and intuition, these methods overlook the latent intercellular relationships driven by the functional mechanisms of biological systems and the inherent quality issues of the raw sequencing data. Therefore, a series of structured methods has emerged. Although they employ various heuristic rules to capture intricate intercellular relationships and enhance the raw sequencing data, these methods often neglect biological prior knowledge. This omission incurs substantial overhead and yields suboptimal graph representations, hindering the utility of ML models. To address these issues, we propose DOGMA, a data-centric framework designed for the structural reshaping and semantic enhancement of raw data through multi-level biological prior knowledge. Transcending reliance on purely data-driven heuristics, DOGMA provides a prior-guided graph construction pipeline that integrates statistical alignment with Cell Ontology and phylogenetic structure for biologically grounded cell-graph construction and robust cross-species alignment. Furthermore, Gene Ontology is utilized to bridge the feature-level semantic gap by incorporating functional priors. In complex multi-species and multi-organ benchmarks, DOGMA exhibits strong robustness in strict zero-shot cell-type evaluation and sample efficiency while using substantially lower GPU memory and inference time in downstream evaluation.