Systematic evaluation of Single-Cell Multimodal Data Integration for Comprehensive Human Reference Atlas

We systematically evaluated experimental and computational strategies for integrating multimodal single-cell and single-nucleus genomics data in complex human tissues. Using human renal cortex as the primary tissue, we generated a benchmarking dataset comprising 3′ and 5′ single-cell RNA sequencing (scRNA-seq) as well as paired single-nucleus RNA sequencing and chromatin accessibility profiling (snRNA-seq and snATAC-seq). Samples were obtained from healthy adult donors undergoing nephrectomy, resulting in 33 kidney cortex samples from 19 donors. In total, over 119,000 high-quality cells and nuclei were profiled. The study evaluates horizontal, vertical, and global multimodal integration strategies and introduces an interpretable machine-learning framework (scOMM) to harmonize annotations and benchmark modality-specific contributions to cell type and cell state resolution. The datasets made available through dbGaP include raw sequencing data and associated metadata supporting reproducible evaluation of multimodal integration strategies in human tissues. ]]>
This study includes kidney cortex samples from 21 adult patients undergoing total nephrectomy. Inclusion Criteria: All patients over the age of 18 years undergoing total nephrectomy per the discretion of their surgeon. Exclusion Criteria: • Unable to provide informed consent • Baseline estimated GFR<30 ml/min/1.73 m2 • Positive urine pregnancy test or pregnancy • Vulnerable populations, including the incarcerated or institutionalized • If the surgeon believes it will be unsafe to obtain kidney tissue for any reason • Autosomal dominant polycystic kidney disease • Atrophic kidney • Chronic pyelonephritis • Urinary Tract Infection • Age > 65 years may not be eligible as per the University of Michigan's research activation committee. This was monitored and enforced when applicable. Rationale for Participant Selection: Patients of both sexes were recruited for this study and all races and ethnicities were enrolled for this study. We excluded patients with advanced CKD because morphometric and transcriptomic analysis were unlikely to be helpful in patients with extremely scarred kidney tissue. ]]>