# Contrastive Deep Learning for Variant Detection in Wastewater Genomic Sequencing

arXiv: https://arxiv.org/abs/2512.03158 · HTML: https://mlsanity.com/paper/2512.03158/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 13 of its 41 references that are in the map.
- First posted on arXiv 2 Dec 2025.

## Builds on (most cited first, 13 of 13)

- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [Representation Learning with Contrastive Predictive Coding](https://mlsanity.com/paper/1807.03748/) (2018)
- [Momentum Contrast for Unsupervised Visual Representation Learning](https://mlsanity.com/paper/1911.05722/) (2019)
- [Neural Discrete Representation Learning](https://mlsanity.com/paper/1711.00937/) (2017)
- [Estimating or Propagating Gradients Through Stochastic Neurons for Conditional Computation](https://mlsanity.com/paper/1308.3432/) (2013)
- [Generating Diverse High-Fidelity Images with VQ-VAE-2](https://mlsanity.com/paper/1906.00446/) (2019)
- [Generating Sentences from a Continuous Space](https://mlsanity.com/paper/1511.06349/) (2015)
- [Jukebox: A Generative Model for Music](https://mlsanity.com/paper/2005.00341/) (2020)
- [Parallel WaveNet: Fast High-Fidelity Speech Synthesis](https://mlsanity.com/paper/1711.10433/) (2017)
- [DNABERT-2: Efficient Foundation Model and Benchmark For Multi-Species Genome](https://mlsanity.com/paper/2306.15006/) (2023)
- [Not All Image Regions Matter: Masked Vector Quantization for Autoregressive Image Generation](https://mlsanity.com/paper/2305.13607/) (2023)
- [Learning Hierarchical Features from Generative Models](https://mlsanity.com/paper/1702.08396/) (2017)

## Abstract (arXiv)

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 to 0.42), while 128-dimensional embeddings achieve +42% improvement (0.31 to 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.