Bias reduction improves accuracy and informativity of high-throughput sequencing chimerism assays

•Bias precludes the use of a significant fraction of markers, affecting informativity.•Data-analytical bias-correction improves accuracy under all circumstances.•Bias-correction improves sensitivity affording use of type II markers in practice.•Also markers considered optimal (type-I) can suffer clinically important bias.•Assay optimization strategies may further reduce bias and increase sensitivity.