Tranzillo, M. | bioRxiv Science

bioRxiv2026

Discovery of microbial intergenic features with genomic language modeling and multimodal search

Systematic characterization of microbial noncoding regions is limited by two distinct challenges: discovery of conserved sequence features without predefined motifs and functional interpretation of newly identified elements. We address these challenges by training a sparse autoencoder on genomic language model (gLM2) representations to identify intergenic sequence features without prior annotation, and by implementing multimodal search to generate functional hypotheses from conserved associations with neighboring proteins, RNA families, and genomic organization. This framework uncovered divergent, previously uncharacterized noncoding elements, including candidate regulatory DNA sequences and structured RNAs not captured by existing annotation models. gLM2-derived intergenic features can be explored through SeqHub's multimodal search, freely available for academic use at seqhub.org.

microbiology↗

bioRxiv2026

Linear-time prediction of proteome-scale microbial protein interactions

Protein-protein interactions (PPIs) underpin biological function, yet proteome-scale interaction prediction remains bottlenecked by the quadratic computational complexity of all-vs-all pairwise comparisons. Here, we present FlashPPI, a contrastive learning framework, grounded in residue-level interactions, that enables linear-time prediction of physical protein interfaces across a microbial proteome. By leveraging a genomic language model that captures cross-protein co-evolutionary signals from metagenomic sequences, FlashPPI aligns interacting partners in a shared latent space. We demonstrate a four-fold performance increase over existing sequence-based methods, while reducing proteome-wide screening time from days to minutes. Crucially, FlashPPI achieves comparable screening performance to state-of-the-art structure-folding models at a fraction of the computational cost. Finally, we integrate FlashPPI into seqhub.org, an interactive web platform that combines predicted networks with functional annotations and genomic context, making proteome-wide network analysis rapid and accessible for microbial discovery.

molecular biology↗