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bioRxiv · 10.1101/2025.08.01.667781

Approaching an Error-Free Diploid Human Genome

Chu, Y.·Huang, Z.·Shao, C.·Guo, S.·Yu, X.·Wang, J.·Tian, Y.·Chen, J.·Li, R.·He, Y.·Yu, J.·Huang, J.·Gao, Z.·Kang, Y.
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Abstract

Complete human genomes now resolve regions long inaccessible to genetic analysis, yet repetitive and structurally complex sequences remain prone to assembly errors because of limitations in current assembly algorithms. We introduce a support-based framework founded on the principle that each sequencing read provides independent evidence for the underlying genome sequence. Implemented through Sufficient Alignment Support (SAS), the framework identifies regions lacking concordant read support, localizes residual errors, and guides correction. Applying SAS to T2T-YAO, a haplotype-resolved Han Chinese genome, produced a support-validated assembly in which nearly all sequences outside unresolved rDNA arrays and long homopolymer tracts are supported by independent sequencing evidence. This work establishes a scalable framework for genome validation and provides a support-validated East Asian diploid reference for investigating human genomic diversity.

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Chu, Y., Huang, Z., Shao, C., Guo, S., Yu, X., Wang, J., Tian, Y., Chen, J., Li, R., He, Y., Yu, J., Huang, J., Gao, Z., Kang, Y.. 2025-08-01. Approaching an Error-Free Diploid Human Genome. https://doi.org/10.1101/2025.08.01.667781

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