bioRxiv Science⌕ Search

bioRxiv · 10.64898/2026.05.02.722381

Learning the Language of the Microbiome with Transformers

Abstract

Self-supervised pretraining has become central to biological machine learning, yet microbiome data remains comparatively underexplored in terms of both modeling approaches and evaluation frameworks. To address this gap, we present Atlas, a pretraining dataset of 539,308 microbiome datapoints from the MGnify database. Using Atlas, we train the Waypoint family of microbiome foundation models: a series of GPT-2 style causal language models ranging from 6M to 170M parameters. We also introduce Compass, a curated benchmark of eight predictive tasks spanning biome classification, drug-microbiome interactions, drug degradation, and infant gut development. Using this benchmark, we compare the performance of Waypoint models against classical baselines and the existing MGM foundation model. Our results show that pretraining leads to consistent and significant improvements in downstream task performance, that both dataset scale and tokenization strategy impact model quality, that pretraining is essential for achieving favorable scaling behavior and that representations learned during pretraining generalise between microbiome domains. Furthermore, pretrained transformer models begin to reliably outperform classical methods once training data exceeds roughly 10,000 examples - a threshold that is attainable for modern microbiome studies. Finally, we demonstrate that the Waypoint models achieve state-of-the-art performance among microbiome foundation models. Overall, our work highlights the importance of large-scale self-supervised pretraining in this domain and establishes Atlas, Compass, and the Waypoint models as valuable resources for the research community in this emerging field.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Treloar, N. J., Ur-Rehman, S., Yang, J.. 2026-05-06. Learning the Language of the Microbiome with Transformers. https://doi.org/10.64898/2026.05.02.722381

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

CellChat Hotspot: A Targeted Approach to Cell Cell Communication Analysis With Spatial transcriptomics Validation.

Abstract. In recent years, single cell RNA sequencing (scRNA seq) has enabled the investigation of intercellular communication through Cell Cell Communication (CCC) tools such as CellChat. Despite their potential, these approaches remain challenging to interpret, particularly when global analyses generate complex interaction networks that may include biologically irrelevant signals. To address this limitation, we developed a framework termed CellChat Hotspot, designed to improve the biological interpretability of inferred communication networks. This approach integrates gene set enrichment analysis with a context driven filtering strategy, selecting both genes and cells based on their functional relevance prior to communication inference. Applied to stage II colon cancer data, CellChat Hotspot enabled the identification of condition-specific interaction patterns associated with recurrence. Non recurrent patients showed enrichment of immune related processes, whereas recurrent cases were characterized by pathways associated with invasion and metastasis. Notably, a loss of interaction in the HSPG pathway between CALB1+ and stromal cells was observed in recurrent patients, suggesting a potential disruption of cell matrix adhesion mechanisms. To verify the reliability of this finding, we applied the framework to spatial transcriptomics data, which confirmed the presence of the HSPG2 DAG1 interaction in non-recurrent tumors and its near absence in recurrent ones. Overall, this framework provides a biologically guided strategy for studying intercellular communication in complex systems such as the tumor microenvironment.

bioinformatics↗

SIFT: Syncmer-Informed Selection of Haplotypes for T2T Imputation

Genome patching improves the completeness of fragmented assemblies by filling unresolved gaps with sequences from reference genomes. Pangenome panels provide diverse candidate haplotypes for this task, but identifying suitable references efficiently becomes increasingly challenging as these panels grow. We present SIFT, a compressed indexing method for selecting reference haplotypes for genome patching with ImpuT2T. SIFT combines closed-syncmer parsing, phrase-level indexing, and pseudo-maximal exact match (pseudo-MEM) queries. Closed syncmers provide a context-independent parsing rule with bounded distances between consecutive selected positions, enabling consistent parsing of reference and query sequences. We demonstrate that two closed syncmers determine the distance at which they can occur consecutively in any string, so that equal substrings of two parses represent identical sequences and no gap sequence need be stored. SIFT indexes the reference parse and its reverse using run-length compressed suffix arrays and adapts the Boyer-Moore-Li search procedure to identify pseudo-MEMs between the reference parse and query parse. It then aggregates matching evidence to identify candidate reference haplotypes for downstream patching. This framework connects compressed sequence indexing with haplotype selection and provides a basis for querying large reference panels at the phrase level. SIFT is publicly available under the GNU license at https://github.com/EddieFerro/SIFT.

bioinformatics↗

Assessing the Capacity of Genomic Language Models to Generate Informative Embeddings of Viral Genome Fragments

Genomic language models (gLMs) trained on large volumes of nucleotide sequences are becoming an alternative to classical methods in metagenomic analysis, particularly for studying genomic "dark matter". In this work, we investigate the ability of four gLMs (DNABERT-2, DNABERT-S, ViraLM, and Evo2-7B) to generate taxonomically informative vector representations of short viral genome fragments. We constructed a balanced reference dataset of viruses based on the ICTV Virus Metadata Resource and compared the representations generated by gLMs with conventional k-mer profiles and MinHash sketches using clustering and neighborhood-based metrics (adjusted Rand index (ARI), precision@k, and CROSS precision@k). On the reference dataset, three of the four gLMs outperformed the 4-mer profile in terms of ARI and precision@5 under the same evaluation protocol. The best performance was generally achieved by intermediate model layers. Conventional k-mer profiles consistently outperformed MinHash sketches. We further evaluated the methods on two viral orders (egoviruses and mriyaviruses) absent from the reference dataset, with model layers and k-mer lengths selected exclusively on the reference dataset. DNABERT-S showed the most consistently strong performance across these two orders, ranking first on mriyaviruses and second on egoviruses, while k-mer profiles with Jensen-Shannon distance remained competitive. We also observed the consistency of representations between forward fragments and their reverse complements. Overall, the best-performing gLMs surpassed conventional baselines, although their advantage depended on the dataset and evaluation metric. The consistently strong performance of DNABERT-S suggests a potential benefit of contrastive fine-tuning and indicates that larger models are not necessarily more effective for generating taxonomically informative representations.

bioinformatics↗