Auditable recovery of single-cell RNA-seq zeros with SPARE

Abstract

In Single-cell RNA-seq, observed zeroes are the mix between biological absence and technical limitations. However, current evaluation metrics fail to distinguish between these two states, focusing on reconstruction accuracy rather than the biological validity of edits. We introduce SPARE, a partition-aware framework that audits the imputation process by cataloging observed zeros as edited, unchanged, or marker-vetoed prior to sequence reconstruction. Across multiple tissue benchmarks, SPARE successfully recovered masked expression while cataloging edit burden, marker leakage and raw-state movement. Protein and disease-context audits showed that recovered expression must be accepted, restricted or rejected endpoint by endpoint. SPARE reframes imputation as auditable zero editing rather than generic matrix completion.