SenNet Portal: Build, Optimization and Usage

Abstract Cellular senescence is a hallmark of aging and a driver of functional decline across tissues, yet its heterogeneity and context dependence have limited systematic study. The Common Fund’s Cellular Senescence Network (SenNet) Program addresses this challenge by generating multimodal, multi-tissue datasets that profile senescent cells across the human lifespan and complementary mouse models. The SenNet Data Portal (https://data.sennetconsortium.org) serves as the public gateway to these resources, providing open access to harmonized single-cell, spatial, imaging, transcriptomic, and proteomic data; senescence biomarker catalogs; and standardized protocols that can be used to comprehensively identify and characterize senescent cells in mouse and human tissue. As of April 2026, the portal hosts 2,041 publicly available human and mouse datasets across 15 organs using 6 general assay types. Experts from 13 Tissue Mapping Centers (TMCs) and 12 Technology Development and Application (TDAs) components contribute tissue data, analyze data, identify senescent biomarkers, and agree on panels for cross-tissue antibody harmonization. They also register human tissue data into the Human Reference Atlas (HRA) and develop user interfaces for the multiscale and multimodal exploration of this data. Built on a scalable hybrid cloud microservices architecture by the Consortium Organization and Data Coordinating Center (CODCC), the Portal enables data submission, management, integrated analysis, spatial context mapping, and harmonized access to cross-species data critical for aging research. This paper presents user needs, the Portal’s architecture, data processing workflows, and senescence-focused analytical tools; usage scenarios illustrating applications in biomarker discovery, quality benchmarking, hypothesis generation, spatial analysis, cost-efficient profiling, and cell distance distribution analysis; and utility and usage by the larger researcher community. Current limitations and planned extensions—including expanded spatial-omics releases and improved tools for senotype characterization—are discussed. SenNet protocols, code, and user interfaces are freely available on https://docs.sennetconsortium.org/apis. Competing Interest Statement In the past three years, R.S. has received compensation from Bristol-Myers Squibb, ImmunAI, Resolve Biosciences, Nanostring, 10X Genomics, Neptune Bio, and the NYC Pandemic Response Lab. R.S. is a co-founder and equity holder of Neptune Bio. N.G. is a co-founder and equity owner of Datavisyn. R.F. is scientific founder and adviser for IsoPlexis, Singleron Biotechnologies, and AtlasXomics. The interests of R.F. were reviewed and managed by Yale University Provost's Office in accordance with the University's conflict of interest policies. All other authors declare no competing interests. Footnotes ↵+ Full list of authors included in SenNet Team is available at the end of the paper This version of the manuscript has been revised to address reviewer comments from a journal.