Paper List
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Pharmacophore-based design by learning on voxel grids
This paper addresses the computational bottleneck and limited novelty in conventional pharmacophore-based virtual screening by introducing a voxel cap...
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CONFIDE: Hallucination Assessment for Reliable Biomolecular Structure Prediction and Design
This paper addresses the critical limitation of current protein structure prediction models (like AlphaFold3) where high-confidence scores (pLDDT) can...
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On the Approximation of Phylogenetic Distance Functions by Artificial Neural Networks
This paper addresses the core challenge of developing computationally efficient and scalable neural network architectures that can learn accurate phyl...
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EcoCast: A Spatio-Temporal Model for Continual Biodiversity and Climate Risk Forecasting
This paper addresses the critical bottleneck in conservation: the lack of timely, high-resolution, near-term forecasts of species distribution shifts ...
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Training Dynamics of Learning 3D-Rotational Equivariance
This work addresses the core dilemma of whether to use computationally expensive equivariant architectures or faster symmetry-agnostic models with dat...
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Fast and Accurate Node-Age Estimation Under Fossil Calibration Uncertainty Using the Adjusted Pairwise Likelihood
This paper addresses the dual challenge of computational inefficiency and sensitivity to fossil calibration errors in Bayesian divergence time estimat...
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Few-shot Protein Fitness Prediction via In-context Learning and Test-time Training
This paper addresses the core challenge of accurately predicting protein fitness with only a handful of experimental observations, where data collecti...
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scCluBench: Comprehensive Benchmarking of Clustering Algorithms for Single-Cell RNA Sequencing
This paper addresses the critical gap of fragmented and non-standardized benchmarking in single-cell RNA-seq clustering, which hinders objective compa...
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.