sc-SPLASH — Reference-Free Discovery for Single-Cell and Spatial Transcriptomics

sc-SPLASH extends the SPLASH statistical framework to barcoded scRNA-seq (10x Chromium) and spatial transcriptomics (10x Visium), enabling reference-free, statistics-first discovery of transcriptomic variation without a reference genome. Its standalone BKC preprocessing submodule is ~50× faster than UMI-tools, and the pipeline has demonstrated discovery of novel secreted proteins in non-model organisms, tumor-associated mutations, and spatially-regulated alternative splicing. Published in Nature Biotechnology (April 2026).

sc-SPLASH — Statistics-First Reference-Free Single-Cell Discovery

Source: github.com/refresh-bio/SPLASH | Published in Nature Biotechnology (April 2026)

Reference-free, statistics-first discovery for 10x Chromium scRNA-seq and 10x Visium spatial data
BKC preprocessing submodule: ~50× faster than UMI-tools (standalone use supported)
Discovers novel transcriptomic events: secreted proteins, alternative splicing, tumor mutations
No reference genome required — unbiased discovery across any organism
Preprint on bioRxiv (December 2024); peer-reviewed in Nature Biotechnology (April 2026)