RESUMO
RNA velocity estimation is a potentially powerful tool to reveal the directionality of transcriptional changes in single-cell RNA-sequencing data, but it lacks accuracy, absent advanced metabolic labeling techniques. We developed an approach, TopicVelo, that disentangles simultaneous, yet distinct, dynamics by using a probabilistic topic model, a highly interpretable form of latent space factorization, to infer cells and genes associated with individual processes, thereby capturing cellular pluripotency or multifaceted functionality. Focusing on process-associated cells and genes enables accurate estimation of process-specific velocities via a master equation for a transcriptional burst model accounting for intrinsic stochasticity. The method obtains a global transition matrix by leveraging cell topic weights to integrate process-specific signals. In challenging systems, this method accurately recovers complex transitions and terminal states, while our use of first-passage time analysis provides insights into transient transitions. These results expand the limits of RNA velocity, empowering future studies of cell fate and functional responses.
Assuntos
Diferenciação Celular , Análise de Classes Latentes , Análise da Expressão Gênica de Célula Única , Transcrição Gênica , Animais , Humanos , Camundongos , Diferenciação Celular/genética , Conjuntos de Dados como Assunto , Biologia do Desenvolvimento , Hematopoese/genética , Imunidade Inata/genética , Inflamação/genética , Linfócitos/citologia , Linfócitos/imunologia , Probabilidade , Reprodutibilidade dos Testes , Análise da Expressão Gênica de Célula Única/métodos , Pele/imunologia , Pele/patologia , Processos Estocásticos , Fatores de TempoRESUMO
RNA velocity estimation is a potentially powerful tool to reveal the directionality of transcriptional changes in single-cell RNA-seq data, but it lacks accuracy, absent advanced metabolic labeling techniques. We developed a novel approach, TopicVelo, that disentangles simultaneous, yet distinct, dynamics by using a probabilistic topic model, a highly interpretable form of latent space factorization, to infer cells and genes associated with individual processes, thereby capturing cellular pluripotency or multifaceted functionality. Focusing on process-associated cells and genes enables accurate estimation of process-specific velocities via a master equation for a transcriptional burst model accounting for intrinsic stochasticity. The method obtains a global transition matrix by leveraging cell topic weights to integrate process-specific signals. In challenging systems, this method accurately recovers complex transitions and terminal states, while our novel use of first-passage time analysis provides insights into transient transitions. These results expand the limits of RNA velocity, empowering future studies of cell fate and functional responses.
