Paper List
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Simulation and inference methods for non-Markovian stochastic biochemical reaction networks
This paper addresses the computational bottleneck of simulating and performing Bayesian inference for non-Markovian biochemical systems with history-d...
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Translating Measures onto Mechanisms: The Cognitive Relevance of Higher-Order Information
This review addresses the core challenge of translating abstract higher-order information theory metrics (e.g., synergy, redundancy) into defensible, ...
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Emergent Bayesian Behaviour and Optimal Cue Combination in LLMs
This paper addresses the critical gap in understanding whether LLMs spontaneously develop human-like Bayesian strategies for processing uncertain info...
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Vessel Network Topology in Molecular Communication: Insights from Experiments and Theory
This work addresses the critical lack of experimentally validated channel models for molecular communication within complex vessel networks, which is ...
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Modulation of DNA rheology by a transcription factor that forms aging microgels
This work addresses the fundamental question of how the transcription factor NANOG, essential for embryonic stem cell pluripotency, physically regulat...
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Imperfect molecular detection renormalizes apparent kinetic rates in stochastic gene regulatory networks
This paper addresses the core challenge of distinguishing genuine stochastic dynamics of gene regulatory networks from artifacts introduced by imperfe...
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Approximate Bayesian Inference on Mechanisms of Network Growth and Evolution
This paper addresses the core challenge of inferring the relative contributions of multiple, simultaneous generative mechanisms in network formation w...
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An AI Implementation Science Study to Improve Trustworthy Data in a Large Healthcare System
This paper addresses the critical gap between theoretical AI research and real-world clinical implementation by providing a practical framework for as...
SpikGPT: A High-Accuracy and Interpretable Spiking Attention Framework for Single-Cell Annotation
Department of Biomedical Informatics, Emory University | Department of Surgery, Duke University
The 30-Second View
IN SHORT: This paper addresses the core challenge of robust single-cell annotation across heterogeneous datasets with batch effects and the critical need to identify previously unseen cell populations.
Innovation (TL;DR)
- Methodology First integration of spiking neural networks with transformer architecture for single-cell analysis, using Leaky Integrate-and-Fire (LIF) neurons in a multi-head Spiking Self-Attention mechanism for energy-efficient computation.
- Methodology Novel two-step embedding expansion strategy: repeating cell embeddings along feature channels (default m=300) and temporal dimensions (default T=4) to enhance representation richness and training stability.
- Biology Confidence-based rejection mechanism that successfully identifies 97% of unseen 'alpha cells' as 'Unknown' in pancreas datasets, enabling robust detection of novel cell types absent from training data.
Key conclusions
- SpikGPT achieves accuracy of 0.991 on SAHR dataset and 0.920 on HLCA dataset, outperforming or matching 8 benchmark methods including scGPT, CCA, and scPred.
- The model demonstrates superior robustness to batch effects, maintaining macro F1-score of 0.711 on heterogeneous HLCA data where traditional methods like SingleR drop to 0.207 F1-score.
- SpikGPT successfully identifies 97% of unseen 'alpha cells' as 'Unknown' using confidence thresholding (p<0.05), enabling reliable detection of novel cell populations.
Abstract: Accurate and scalable cell type annotation remains a challenge in single-cell transcriptomics, especially when datasets exhibit strong batch effects or contain previously unseen cell populations. Here we introduce SpikGPT, a hybrid deep learning framework that integrates scGPT-derived cell embeddings with a spiking Transformer architecture to achieve efficient and robust annotation. scGPT provides biologically informed dense representations of each cell, which are further processed by a multi-head Spiking Self-Attention mechanism, energy-efficient feature extraction. Across multiple benchmark datasets, SpikGPT consistently matches or exceeds the performance of leading annotation tools. Notably, SpikGPT uniquely identifies unseen cell types by assigning low-confidence predictions to an 'Unknown' category, allowing accurate rejection of cell states absent from the training reference. Together, these results demonstrate that SpikGPT is a versatile and reliable annotation tool capable of generalizing across datasets, resolving complex cellular heterogeneity, and facilitating discovery of novel or disease-associated cell populations.