Small open reading frames (smORFs) shorter than 100 codons are widespread and perform essential roles in microorganisms, where they encode proteins active in several cell functions, including signal pathways, stress response, and antibacterial activities. However, the ecology, distribution and role of small proteins in the global microbiome remain unknown. Here, we construct a global microbial smORFs catalog (GMSC) derived from 63,410 publicly available metagenomes across 75 distinct habitats and 87,920 high-quality isolate genomes. GMSC contains 965 million non-redundant smORFs with comprehensive annotations. We find that archaea harbor more smORFs proportionally than bacteria. We moreover provide a tool called GMSC-mapper to identify and annotate small proteins from microbial (meta)genomes. Overall, this publicly-available resource demonstrates the immense and underexplored diversity of small proteins.

In recent years, there has been an exponential growth in sequencing projects due to accelerated technological advances, leading to a significant increase in the amount of data and resulting in new challenges for biological sequence analysis. Consequently, the use of techniques capable of analyzing large amounts of data has been explored, such as machine learning (ML) algorithms. ML algorithms are being used to analyze and classify biological sequences, despite the intrinsic difficulty in extracting and finding representative biological sequence methods suitable for them. Thereby, extracting numerical features to represent sequences makes it statistically feasible to use universal concepts from Information Theory, such as Tsallis and Shannon entropy. In this study, we propose a novel Tsallis entropy-based feature extractor to provide useful information to classify biological sequences. To assess its relevance, we prepared five case studies: (1) an analysis of the entropic index q; (2) performance testing of the best entropic indices on new datasets; (3) a comparison made with Shannon entropy and (4) generalized entropies; (5) an investigation of the Tsallis entropy in the context of dimensionality reduction. As a result, our proposal proved to be effective, being superior to Shannon entropy and robust in terms of generalization, and also potentially representative for collecting information in fewer dimensions compared with methods such as Singular Value Decomposition and Uniform Manifold Approximation and Projection.

Small open reading frames (smORFs) shorter than 100 codons are widespread and perform essential roles in microorganisms, where they encode proteins active in several cell functions, including signal pathways, stress response, and antibacterial activities. However, the ecology, distribution and role of small proteins in the global microbiome remain unknown. Here, we constructed a global microbial smORFs catalogue (GMSC) derived from 63,410 publicly available metagenomes across 75 distinct habitats and 87,920 high-quality isolate genomes. GMSC contains 965 million non-redundant smORFs with comprehensive annotations. We found that archaea harbor more small proteins proportionally than bacteria. We moreover provide a tool called GMSC-mapper to identify and annotate small proteins from microbial (meta)genomes. Overall, this publicly-available resource demonstrates the immense and underexplored diversity of small proteins.

The prediction of biological sequence properties has traditionally relied on alignment-based methods that assume evolutionary homology and depend on curated reference databases. This, in turn, limits scalability and sensitivity for large or heterogeneous datasets, remote homologs, short sequences, and rapidly evolving genomic regions. Although Machine-Learning (ML) approaches offer alignment-free alternatives, their broader adoption is limited by: (i) the lack of standardized, externally validated benchmark models across diverse datasets, and (ii) the technical expertise required for feature engineering, model selection, and evaluation. Automated machine learning (AutoML) alleviates these challenges by systematically optimizing representations and models with minimal user intervention. However, most existing frameworks prioritize task-specific model construction and lack mechanisms for preserving trained models as persistent, comparable benchmarks. We introduce BioAutoML-FAST, an end-to-end web platform for automated ML analysis of nucleotide and amino acid sequences. It supports both classification and regression tasks and automates feature extraction, model training, and evaluation without requiring prior user expertise. Uniquely, it serves as a community benchmarking resource, hosting a continuously expanding repository of reusable, standardized models (currently 60) for genomic, transcriptomic, and proteomic applications. Extensive validation on independent datasets demonstrates performance comparable to or exceeding that of state-of-the-art methods, including protein language models such as ESM-2. BioAutoML-FAST is available at https://bioautoml.icmc.usp.br/. This website is free and open to all users, and there is no login requirement.