Biological language model performance depends heavily on pretraining data quality, diversity, and size. While metagenomic datasets feature enormous biological diversity, their utilization as pretraining data has been limited due to challenges in data accessibility, quality filtering and deduplication. Here, we present the Open MetaGenomic (OMG) corpus, a genomic pretraining dataset totalling 3.1T base pairs and 3.3B protein coding sequences, obtained by combining two largest metagenomic dataset repositories (JGI's IMG and EMBL's MGnify). We first document the composition of the dataset and describe the quality filtering steps taken to remove poor quality data. We make the OMG corpus available as a mixed-modality genomic sequence dataset that represents multi-gene encoding genomic sequences with translated amino acids for protein coding sequences, and nucleic acids for intergenic sequences. We train the first mixed-modality genomic language model (gLM2) that leverages genomic context information to learn robust functional representations, as well as coevolutionary signals in protein-protein interfaces and genomic regulatory syntax. Furthermore, we show that deduplication in embedding space can be used to balance the corpus, demonstrating improved performance on downstream tasks. The OMG dataset is publicly hosted on the Hugging Face Hub at https://huggingface.co/datasets/tattabio/OMG and gLM2 is available at https://huggingface.co/tattabio/gLM2_650M.

SUMMARY: Accurate metagenomic taxonomic profiling is critical for understanding microbial communities. However, computational analysis often requires command-line proficiency and high-performance computing resources. To lower these barriers, we developed Metabuli App, an all-in-one desktop application that efficiently runs taxonomic profiling locally on a consumer-grade computer. It features user-friendly graphical interfaces for custom database curation, raw read quality control (QC), taxonomic profiling, and interactive result visualization. AVAILABILITY AND IMPLEMENTATION: GPLv3-licensed source code and prebuilt apps for Windows, macOS, and Linux are available at https://github.com/steineggerlab/Metabuli-App and are archived at https://doi.org/10.5281/zenodo.15876171. Analysis scripts are available at https://github.com/jaebeom-kim/metabuli-app-analysis. The Sankey-based taxonomy visualization component is available at https://github.com/steineggerlab/taxoview for easy integration into other web projects.

SUMMARY: Highly accurate protein structure predictors have generated hundreds of millions of protein structures; these pose a challenge in terms of storage and processing. Here, we present Foldcomp, a novel lossy structure compression algorithm, and indexing system to address this challenge. By using a combination of internal and Cartesian coordinates and a bi-directional NeRF-based strategy, Foldcomp improves the compression ratio by a factor of three compared to the next best method. Its reconstruction error of 0.08 Å is comparable to the best lossy compressor. It is five times faster than the next fastest compressor and competes with the fastest decompressors. With its multi-threading implementation and a Python interface that allows for easy database downloads and efficient querying of protein structures by accession, Foldcomp is a powerful tool for managing and analysing large collections of protein structures. AVAILABILITY AND IMPLEMENTATION: Foldcomp is a free open-source software (GPLv3) and available for Linux, macOS, and Windows at https://foldcomp.foldseek.com. Foldcomp provides the AlphaFold Swiss-Prot (2.9GB), TrEMBL (1.1TB), and ESMatlas HQ (114GB) database ready-for-download.

SUMMARY: MMseqs2 taxonomy is a new tool to assign taxonomic labels to metagenomic contigs. It extracts all possible protein fragments from each contig, quickly retains those that can contribute to taxonomic annotation, assigns them with robust labels and determines the contig's taxonomic identity by weighted voting. Its fragment extraction step is suitable for the analysis of all domains of life. MMseqs2 taxonomy is 2-18× faster than state-of-the-art tools and also contains new modules for creating and manipulating taxonomic reference databases as well as reporting and visualizing taxonomic assignments. AVAILABILITY AND IMPLEMENTATION: MMseqs2 taxonomy is part of the MMseqs2 free open-source software package available for Linux, macOS and Windows at https://mmseqs.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: SpacePHARER (CRISPR Spacer Phage-Host Pair Finder) is a sensitive and fast tool for de novo prediction of phage-host relationships via identifying phage genomes that match CRISPR spacers in genomic or metagenomic data. SpacePHARER gains sensitivity by comparing spacers and phages at the protein level, optimizing its scores for matching very short sequences, and combining evidence from multiple matches, while controlling for false positives. We demonstrate SpacePHARER by searching a comprehensive spacer list against all complete phage genomes. AVAILABILITY AND IMPLEMENTATION: SpacePHARER is available as an open-source (GPLv3), user-friendly command-line software for Linux and macOS: https://github.com/soedinglab/spacepharer. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: The MMseqs2 desktop and web server app facilitates interactive sequence searches through custom protein sequence and profile databases on personal workstations. By eliminating MMseqs2's runtime overhead, we reduced response times to a few seconds at sensitivities close to BLAST. AVAILABILITY AND IMPLEMENTATION: The app is easy to install for non-experts. GPLv3-licensed code, pre-built desktop app packages for Windows, MacOS and Linux, Docker images for the web server application and a demo web server are available at https://search.mmseqs.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: HH-suite is a widely used open source software suite for sensitive sequence similarity searches and protein fold recognition. It is based on pairwise alignment of profile Hidden Markov models (HMMs), which represent multiple sequence alignments of homologous proteins. RESULTS: We developed a single-instruction multiple-data (SIMD) vectorized implementation of the Viterbi algorithm for profile HMM alignment and introduced various other speed-ups. These accelerated the search methods HHsearch by a factor 4 and HHblits by a factor 2 over the previous version 2.0.16. HHblits3 is ∼10× faster than PSI-BLAST and ∼20× faster than HMMER3. Jobs to perform HHsearch and HHblits searches with many query profile HMMs can be parallelized over cores and over cluster servers using OpenMP and message passing interface (MPI). The free, open-source, GPLv3-licensed software is available at https://github.com/soedinglab/hh-suite . CONCLUSION: The added functionalities and increased speed of HHsearch and HHblits should facilitate their use in large-scale protein structure and function prediction, e.g. in metagenomics and genomics projects.