A new study led by Jonathan Karin, Reshef Mintz, Dr. Barak Raveh and Dr. Mor Nitzan from Hebrew University, published in Nature Computational Science, introduces a new framework for interpreting single-cell and spatial omics data by monitoring deep neural networks training dynamics. The research aims to address the inherent ambiguities in cell annotations and offers a novel approach for understanding complex biological data.
Single-cell and spatial omics data have transformed our ability to explore cellular diversity and cellular behaviors in health and disease. However, the interpretation of these high-dimensional datasets is challenging, primarily due to the difficulty of assigning discrete and accurate annotations, such as cell types or states, to heterogeneous cell populations. These annotations are often subjective, noisy, and incomplete, making it difficult to extract meaningful insights from the data.
The researchers developed a new framework, Annotatability, which helps identify mismatches in cell annotations and better characterizes biological data structures. By monitoring the dynamics and difficulty of training a deep neural network over annotated data, Annotatability identifies areas where cell annotations are ambiguous or erroneous. The approach also highlights intermediate cell states and the complex, continuous nature of cellular development.
As part of the study, the team introduced a signal-aware graph embedding method that enables more precise downstream analysis of biological signals. This technique captures cellular communities associated with target signals and facilitates the exploration of cellular heterogeneity, developmental pathways, and disease trajectories.
The study demonstrates the applicability of Annotatability across a range of single-cell RNA sequencing and spatial omics datasets. Notable findings include the identification of erroneous annotations, delineation of developmental and disease-related cell states, and better characterization of cellular heterogeneity. The results highlight the potential of this framework for unraveling complex cellular behaviors and advancing our understanding of both health and disease at the single-cell level.
The researchers' work presents a significant step forward in genomic data interpretation, offering a powerful tool for unraveling cellular diversity and enhancing our ability to study the dynamics of health and disease.
Karin J, Mintz R, Raveh B, Nitzan M.
Interpreting single-cell and spatial omics data using deep neural network training dynamics.
Nat Comput Sci. 2024 Dec;4(12):941-954. doi: 10.1038/s43588-024-00721-5