Multi-omics analysis of a pig-to-human decedent kidney xenotransplant

In this multi-omic investigation of a pig-to-human kidney xenotransplant maintained for more than a month in a brain-dead human decedent, researchers combined single-cell and spatial transcriptomics, immune-repertoire sequencing, and deep longitudinal serum proteomics to reconstruct the molecular events driving graft adaptation and rejection. The Proteograph^® proteomics data — generated from 63 timepoints using MS-based, nanoparticle-enabled profiling — played an essential role by capturing circulating markers of inflammation, complement activation, and tissue injury that paralleled and often preceded transcriptional evidence of graft decline.

A unique strength of the MS-based approach was its ability to disentangle mixed human–pig protein signals within the recipient’s bloodstream. Because xenotransplantation creates a truly hybrid proteome environment, the capacity to accurately distinguish pig-derived peptides from human-derived proteins allowed the study to track graft-specific injury responses alongside host immune activation. This dual-species resolution enabled precise mapping of cross-species signaling, macrophage activation, and interferon-responsive pathways that standard affinity assays cannot resolve.

By connecting these serum-level protein dynamics with the cellular, spatial, and clonal signatures observed within the graft, the study demonstrates how high-resolution MS proteomics provides an indispensable, unbiased view of xenograft biology. The approach not only detects early molecular hallmarks of rejection but establishes a scalable framework for monitoring xenotransplant performance — offering a pathway to earlier intervention and more informed clinical decision-making in future trials.