Paper List
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PanFoMa: A Lightweight Foundation Model and Benchmark for Pan-Cancer
This paper addresses the dual challenge of achieving computational efficiency without sacrificing accuracy in whole-transcriptome single-cell represen...
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Beyond Bayesian Inference: The Correlation Integral Likelihood Framework and Gradient Flow Methods for Deterministic Sampling
This paper addresses the core challenge of calibrating complex biological models (e.g., PDEs, agent-based models) with incomplete, noisy, or heterogen...
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Contrastive Deep Learning for Variant Detection in Wastewater Genomic Sequencing
This paper addresses the core challenge of detecting viral variants in wastewater sequencing data without reference genomes or labeled annotations, ov...
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SpikGPT: A High-Accuracy and Interpretable Spiking Attention Framework for Single-Cell Annotation
This paper addresses the core challenge of robust single-cell annotation across heterogeneous datasets with batch effects and the critical need to ide...
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Unlocking hidden biomolecular conformational landscapes in diffusion models at inference time
This paper addresses the core challenge of efficiently and accurately sampling the conformational landscape of biomolecules from diffusion-based struc...
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Learning From Limited Data and Feedback for Cell Culture Process Monitoring: A Comparative Study
This paper addresses the core challenge of developing accurate real-time bioprocess monitoring soft sensors under severe data constraints: limited his...
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Cell-cell communication inference and analysis: biological mechanisms, computational approaches, and future opportunities
This review addresses the critical need for a systematic framework to navigate the rapidly expanding landscape of computational methods for inferring ...
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Generating a Contact Matrix for Aged Care Settings in Australia: an agent-based model study
This study addresses the critical gap in understanding heterogeneous contact patterns within aged care facilities, where existing population-level con...
Contrastive Deep Learning for Variant Detection in Wastewater Genomic Sequencing
Georgia State University, Atlanta, Georgia, USA
The 30-Second View
IN SHORT: This paper addresses the core challenge of detecting viral variants in wastewater sequencing data without reference genomes or labeled annotations, overcoming issues of high noise, low coverage, and fragmented reads.
Innovation (TL;DR)
- Methodology First comprehensive application of VQ-VAE with EMA quantization to wastewater genomic surveillance, achieving 99.52% token-level reconstruction accuracy with 19.73% codebook utilization.
- Methodology Integration of masked reconstruction pretraining (BERT-style) maintaining ~95% accuracy under 20% token corruption, enabling robust inference with missing/low-quality data.
- Methodology Contrastive fine-tuning with varying embedding dimensions showing +35% (64-dim) and +42% (128-dim) Silhouette score improvements, establishing representation capacity impact on variant discrimination.
Key conclusions
- VQ-VAE achieves 99.52% mean token-level accuracy and 56.33% exact sequence match rate on SARS-CoV-2 wastewater data with 100,000 reads.
- Contrastive fine-tuning improves clustering performance by +35% (0.31→0.42) with 64-dim embeddings and +42% (0.31→0.44) with 128-dim embeddings.
- The framework maintains efficient codebook utilization (19.73%, 101 of 512 codes active) while providing robust performance under data corruption.
Abstract: Wastewater-based genomic surveillance has emerged as a powerful tool for population-level viral monitoring, offering comprehensive insights into circulating viral variants across entire communities. However, this approach faces significant computational challenges stemming from high sequencing noise, low viral coverage, fragmented reads, and the complete absence of labeled variant annotations. Traditional reference-based variant calling pipelines struggle with novel mutations and require extensive computational resources. We present a comprehensive framework for unsupervised viral variant detection using Vector-Quantized Variational Autoencoders (VQ-VAE) that learns discrete codebooks of genomic patterns from k-mer tokenized sequences without requiring reference genomes or variant labels. Our approach extends the base VQ-VAE architecture with masked reconstruction pretraining for robustness to missing data and contrastive learning for highly discriminative embeddings. Evaluated on SARS-CoV-2 wastewater sequencing data comprising approximately 100,000 reads, our VQ-VAE achieves 99.52% mean token-level accuracy and 56.33% exact sequence match rate while maintaining 19.73% codebook utilization (101 of 512 codes active), demonstrating efficient discrete representation learning. Contrastive fine-tuning with different projection dimensions yields substantial clustering improvements: 64-dimensional embeddings achieve +35% Silhouette score improvement (0.31→0.42), while 128-dimensional embeddings achieve +42% improvement (0.31→0.44), clearly demonstrating the impact of embedding dimensionality on variant discrimination capability. Our reference-free framework provides a scalable, interpretable approach to genomic surveillance with direct applications to public health monitoring.