Neurosymbolic Learning for Predicting Cell Fate Decisions from Longitudinal Single Cell Transcriptomics in Paediatric Acute Myeloid Leukemia

TL;DR

This study introduces a novel neuro-symbolic AI framework combining deep learning and complexity science to predict and understand cell fate decisions in pediatric AML using longitudinal single-cell transcriptomics, revealing key biomarkers and potential therapeutic targets.

Contribution

It is the first to integrate RNNs, Transformers, and Algorithmic Information Dynamics for modeling AML progression and cell fate trajectories, providing new insights into disease mechanisms.

Findings

Identification of dysregulated epigenetic and developmental patterns.

Prediction of neurodevelopmental and morphogenetic signatures in AML.

Implication of brain-immune axis in AML cell fate regulation.

Abstract

Paediatric Acute Myeloid Leukemia is a complex adaptive ecosystem with high morbidity. Current trajectory inference algorithms struggle to predict causal dynamics in AML progression, including relapse and recurrence risk. We propose a symbolic AI and deep learning framework grounded in complexity science, integrating Recurrent Neural Networks, Transformers, and Algorithmic Information Dynamics to model longitudinal single cell transcriptomics and infer complex state transitions in paediatric AML. We identify key plasticity markers as predictive signatures regulating developmental trajectories. These were derived by integrating deep learning with complex systems based network perturbation analysis and dynamical systems theory to infer high dimensional state space attractors steering AML evolution. Findings reveal dysregulated epigenetic and developmental patterning, with AML cells in maladaptive, reprogrammable plastic states, i.e., developmental arrest blocking terminal differentiation. Predictions forecast neurodevelopmental and morphogenetic signatures guiding AML cell fate bifurcations, suggesting ectoderm mesoderm crosstalk during disrupted differentiation. Neuroplasticity and neurotransmission related transcriptional signals implicate a brain immune hematopoietic axis in AML cell fate cybernetics. This is the first study combining RNNs and AID to predict and decipher longitudinal patterns of cell fate transition trajectories in AML. Our complex systems approach enables causal discovery of predictive biomarkers and therapeutic targets for ecosystem engineering, cancer reversion, precision gene editing, and differentiation therapy, with strong translational potential for precision oncology and patient centered care.