Paper List
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Exactly Solvable Population Model with Square-Root Growth Noise and Cell-Size Regulation
This paper addresses the fundamental gap in understanding how microscopic growth fluctuations, specifically those with size-dependent (square-root) no...
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Assessment of Simulation-based Inference Methods for Stochastic Compartmental Models
This paper addresses the core challenge of performing accurate Bayesian parameter inference for stochastic epidemic models when the likelihood functio...
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Realistic Transition Paths for Large Biomolecular Systems: A Langevin Bridge Approach
This paper addresses the core challenge of generating physically realistic and computationally efficient transition paths between distinct protein con...
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MoRSAIK: Sequence Motif Reactor Simulation, Analysis and Inference Kit in Python
This work addresses the computational bottleneck in simulating prebiotic RNA reactor dynamics by developing a Python package that tracks sequence moti...
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The BEAT-CF Causal Model: A model for guiding the design of trials and observational analyses of cystic fibrosis exacerbations
This paper addresses the critical gap in cystic fibrosis exacerbation management by providing a formal causal framework that integrates expert knowled...
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A Theoretical Framework for the Formation of Large Animal Groups: Topological Coordination, Subgroup Merging, and Velocity Inheritance
This paper addresses the core problem of how large, coordinated animal groups form in nature, challenging the classical view of gradual aggregation by...
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ANNE Apnea Paper
This paper addresses the core challenge of achieving accurate, event-level sleep apnea detection and characterization using a non-intrusive, multimoda...
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DeeDeeExperiment: Building an infrastructure for integrating and managing omics data analysis results in R/Bioconductor
This paper addresses the critical bottleneck of managing and organizing the growing volume of differential expression and functional enrichment analys...
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.