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Main Authors: Celikkanat, Abdulkadir, Masegosa, Andres R., Albertsen, Mads, Nielsen, Thomas D.
Format: Preprint
Published: 2025
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Online Access:https://arxiv.org/abs/2509.26116
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author Celikkanat, Abdulkadir
Masegosa, Andres R.
Albertsen, Mads
Nielsen, Thomas D.
author_facet Celikkanat, Abdulkadir
Masegosa, Andres R.
Albertsen, Mads
Nielsen, Thomas D.
contents Metagenomic binning aims to cluster DNA fragments from mixed microbial samples into their respective genomes, a critical step for downstream analyses of microbial communities. Existing methods rely on deterministic representations, such as k-mer profiles or embeddings from large language models, which fail to capture the uncertainty inherent in DNA sequences arising from inter-species DNA sharing and from fragments with highly similar representations. We present the first probabilistic embedding approach, UncertainGen, for metagenomic binning, representing each DNA fragment as a probability distribution in latent space. Our approach naturally models sequence-level uncertainty, and we provide theoretical guarantees on embedding distinguishability. This probabilistic embedding framework expands the feasible latent space by introducing a data-adaptive metric, which in turn enables more flexible separation of bins/clusters. Experiments on real metagenomic datasets demonstrate the improvements over deterministic k-mer and LLM-based embeddings for the binning task by offering a scalable and lightweight solution for large-scale metagenomic analysis.
format Preprint
id arxiv_https___arxiv_org_abs_2509_26116
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle UncertainGen: Uncertainty-Aware Representations of DNA Sequences for Metagenomic Binning
Celikkanat, Abdulkadir
Masegosa, Andres R.
Albertsen, Mads
Nielsen, Thomas D.
Machine Learning
Computational Engineering, Finance, and Science
Metagenomic binning aims to cluster DNA fragments from mixed microbial samples into their respective genomes, a critical step for downstream analyses of microbial communities. Existing methods rely on deterministic representations, such as k-mer profiles or embeddings from large language models, which fail to capture the uncertainty inherent in DNA sequences arising from inter-species DNA sharing and from fragments with highly similar representations. We present the first probabilistic embedding approach, UncertainGen, for metagenomic binning, representing each DNA fragment as a probability distribution in latent space. Our approach naturally models sequence-level uncertainty, and we provide theoretical guarantees on embedding distinguishability. This probabilistic embedding framework expands the feasible latent space by introducing a data-adaptive metric, which in turn enables more flexible separation of bins/clusters. Experiments on real metagenomic datasets demonstrate the improvements over deterministic k-mer and LLM-based embeddings for the binning task by offering a scalable and lightweight solution for large-scale metagenomic analysis.
title UncertainGen: Uncertainty-Aware Representations of DNA Sequences for Metagenomic Binning
topic Machine Learning
Computational Engineering, Finance, and Science
url https://arxiv.org/abs/2509.26116