Deep Lineage: Single-Cell Lineage Tracing and Fate Inference Using Deep Learning

Recent advances in single-cell RNA-sequencing and lineage tracing techniques have provided valuable insights into the temporal changes in gene expression during development, tumour progression, and disease onset. However, there are few computational methods available to analyze this information to help understand multicellular dynamics. We introduce Deep Lineage, a novel deep-learning method for analyzing time-series single-cell RNA-sequencing with matched lineage-tracing data. Our method accurately predicts early cell fate biases and gene expression profiles at different time points within a clone, surpassing current state-of-the-art methods in fate prediction accuracy. Additionally, through in silico perturbations in cellular reprogramming and hematopoiesis development data, we show that Deep Lineage can accurately model dynamic multicellular responses while identifying key genes and pathways associated with cell fate determination.