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A Diploid Assembly-based Benchmark for Variants in The Major Histocompatibility Complex



Justin M. Zook, Justin M. Wagner, Chen-Shan Chin, Qiandong Zeng, Alexander Dilthey, Tobias Marschall, Mikko Rautiainen, Erik Garrison, Shilpa Garg


Most human genomes are characterized by aligning individual reads to the reference genome, but accurate long reads and linked reads now enable us to construct accurate, phased de novo assemblies. We focus on a medically important, highly variable, 5 million base-pair (bp) region where diploid assembly is particularly useful - the Major Histocompatibility Complex (MHC). Here, we develop a human genome benchmark derived from a diploid assembly for the openly-consented Genome in a Bottle sample HG002. We assemble a single contig for each haplotype, align them to the reference, call phased small and structural variants, and define a small variant benchmark for the MHC, covering 94% of the MHC and 22368 variants smaller than 50 bp, 49% more variants than a mapping-based benchmark. This benchmark reliably identifies errors in mapping-based callsets, and enables performance assessment in regions with much denser, complex variation than regions covered by previous benchmarks.
Nature Communications


genomics, DNA sequencing, major histocompatibility complex, reference materials


Zook, J. , Wagner, J. , Chin, C. , Zeng, Q. , Dilthey, A. , Marschall, T. , Rautiainen, M. , Garrison, E. and Garg, S. (2020), A Diploid Assembly-based Benchmark for Variants in The Major Histocompatibility Complex, Nature Communications, [online], (Accessed May 26, 2024)


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Created September 21, 2020, Updated March 1, 2021