Paper List
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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...
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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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Hierarchical Molecular Language Models (HMLMs)
This paper addresses the core challenge of accurately modeling context-dependent signaling, pathway cross-talk, and temporal dynamics across multiple ...
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Stability analysis of action potential generation using Markov models of voltage‑gated sodium channel isoforms
This work addresses the challenge of systematically characterizing how the high-dimensional parameter space of Markov models for different sodium chan...
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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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EnzyCLIP: A Cross-Attention Dual Encoder Framework with Contrastive Learning for Predicting Enzyme Kinetic Constants
This paper addresses the core challenge of jointly predicting enzyme kinetic parameters (Kcat and Km) by modeling dynamic enzyme-substrate interaction...
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Tissue stress measurements with Bayesian Inversion Stress Microscopy
This paper addresses the core challenge of measuring absolute, tissue-scale mechanical stress without making assumptions about tissue rheology, which ...
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DeepFRI Demystified: Interpretability vs. Accuracy in AI Protein Function Prediction
This study addresses the critical gap between high predictive accuracy and biological interpretability in DeepFRI, revealing that the model often prio...
SpikGPT: A High-Accuracy and Interpretable Spiking Attention Framework for Single-Cell Annotation
Department of Biomedical Informatics, Emory University | Department of Surgery, Duke University
30秒速读
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.
核心创新
- 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.
主要结论
- 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.
摘要: 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.