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Integrating multi-omics technologies to decipher microbiome functions.

Multi-omics approaches have revolutionized our understanding of microbial communities by enabling simultaneous interrogation of genomic, transcriptomic, proteomic, and metabolomic data. The systematic integration and analysis of these deep datasets help decipher the functional roles of microbiomes, providing critical insights into microbial activities, interactions, and dynamics across diverse environments. Biological complexity makes multi-omics analysis of a single, isolated organism demanding but highly informative, yet this complexity increases further when samples comprise hundreds to thousands of individual species. As microbiome research continues to expand into clinical, environmental, and engineered systems, standardized workflows, benchmarked datasets, and community-driven initiatives are essential to ensure reproducibility, standardization and interpretability. Establishing and disseminating best practices for experimental design, data processing, and integrative analyses will be critical for maximizing comparability and scientific rigor across studies. This perspective highlights recent advances in multi-omics microbiome research, outlines key obstacles in data integration and metadata harmonization, and proposes a collaborative roadmap for scalable, FAIR-compliant multi-omics investigations and potentially disruptive Artificial Intelligence (AI) advances comparable to those of AlphaFold in the field of microbiome science.

Multiomics

Consistently processed RNA sequencing data from 50 sources enriched for pediatric data.

Larger cohorts improve the power of tumor gene expression analysis, but the signal is muddied if datasets are processed using different methods or have inaccurate metadata. Here we present five compendia containing consistently processed gene expression data derived from 16,446 diverse RNA sequencing datasets. To create the compendia, we obtained access to RNA sequence data from repositories containing public data as well as clinical partners with access to non-published data. We then assessed the quality, quantified gene expression, harmonized clinical metadata, and released the expression values and metadata without access restrictions. These datasets have been used for diverse projects ranging from identifying similarities between tumor types to assessing how well cell lines recapitulate tumors. They have also been used for n-of-1 analysis to identify genes with unusual expression patterns in a single sample and to infer molecular diagnosis. The comparison to new data is enabled by our dockerized, freely available pipeline. The compendia have been cited in at least 20 publications.

Humans

ClarID: A Human-Readable and Compact Identifier Specification for Biomedical Metadata Integration.

BACKGROUND: In biomedical research, subjects and biospecimens are commonly tracked using simple IDs or UUIDs, which guarantee uniqueness but convey no embedded semantic information. Contextual metadata (such as tissue type, diagnosis, or assay) is often stored separately, making integration, cohort selection, and downstream analysis cumbersome. While structured barcoding systems exist in large consortia (e.g., TCGA, GTEx) or domain-specific contexts (e.g., SPREC, GOLD), no unified, extensible framework currently spans both subjects and biosamples in a human- and machine-readable way. METHODS: We developed ClarID, a domain-agnostic specification that supports two identifier formats: (i) a human-readable form (e.g., 'CNAG_Test-HomSap-00001-LIV-TUM-RNA-C22.0-TRT-P1W' that encodes key metadata such as project, species, subject_id, tissue, assay, disease, timepoint and duration (from that event); and (ii) a compact version named 'stub' (e.g., 'CT01001LTR0N401T1W') optimized for filenames, pipelines, and labeling.ClarID is implemented through an open-source command-line tool, ClarID-Tools, which processes tabular metadata files (CSV/TSV) and uses a YAML-based codebook to generate, decode, and validate identifiers, as well as to create and read QR codes. The tool supports bulk and single-sample processing and allows easy integration with institutional workflows. RESULTS: To demonstrate ClarID's utility, we applied it to datasets from the Genomic Data Commons (GDC), generating interpretable identifiers for more than 113,000 clinical records (subjects) and 4,255 biospecimen records. All materials, including pre-processing scripts, input and encoded data, are publicly available and fully reproducible via the accompanying GitHub repository and Google Colab. CONCLUSIONS: ClarID fills a critical gap between opaque accession numbers and rich metadata schemas by embedding key context directly into structured identifiers. It enhances traceability, facilitates downstream analysis, and remains adaptable to project-specific needs through a configurable codebook. The accompanying ClarID-Tools software is freely available, together with full documentation and reproducible pipelines, at https://github.com/CNAG-Biomedical-Informatics/clarid-tools.

Biosample identifiers

SimpleMicrobiome: An integrated web-based platform for streamlined microbiome data analysis and visualization.

Microbiome studies require multiple analytical steps after initial sequence processing. These steps commonly include data harmonization, preprocessing, taxonomic profiling, diversity analysis, differential abundance testing, predictive modeling, network inference, and preparation of publication-ready outputs. Although robust packages are available for many of these tasks, routine use often depends on command-line workflows, repeated data reformatting, and method-specific scripting. These requirements can limit accessibility for experimental researchers and complicate consistent analysis across interdisciplinary teams. We developed SimpleMicrobiome, a web-based R Shiny platform that integrates established microbiome analysis methods into a single interactive downstream workflow. The application accepts standard abundance, taxonomy, and metadata tables, supports interactive preprocessing and sample filtering, and provides modules for taxa profile visualization, alpha and beta diversity analysis, ANCOM-BC2 and MaAsLin2 differential abundance testing, Random Forest modeling with SHAP-based interpretation, microbial association network inference using SparCC and SPIEC-EASI through NetCoMi, correlation heatmaps, and dbRDA/CAP-style association biplots. The platform is implemented as a modular Shiny application so that preprocessing choices are propagated across downstream analyses, results can be exported as figures and tables, and the same application can be run through the public server, source-code installation, or a Docker image. SimpleMicrobiome consolidates major downstream microbiome analysis tasks in an accessible browser-based environment while retaining links to established analytical frameworks. The platform may reduce technical barriers for non-programming users, improve consistency across exploratory and reporting-oriented analyses, and support collaborative microbiome research. The public application is available at https://simplemicrobiome.mglab.org, the source code is available at https://github.com/yjcho2252/SimpleMicrobiome, and a Docker image for local deployment is available at https://hub.docker.com/r/mglab2252/simplemicrobiome.

differential abundance