Pan-genomics of complex loci in the human genome

Objectives

Despite tremendous progress in genome assembly, recalcitrant genomic loci remain whose sequences cannot be resolved. Such regions are often variable in copy number and such copy number variants (CNVs) have been linked to various disorders, including neuropsychiatric conditions and autism spectrum disorders. “Rearrangement hot spots”, which are regions in the human genome that are particularly vulnerable to deletion and duplication, are especially complex but at the same time often gene rich and potentially involved in diseases. This projects focuses on developing novel graph based algorithms to study such loci.

The group of Tobias Marschall has a long track record of work on algorithms for pangenomics, haplotype reconstrution, genome assembly, and structural variation. This project provides ample opportunities to interact with other group members, with other researchers within the Alpaca network, and with other leading consortia that tackle related questions, including the Human Genome Structural Variation Consortium, the Human Pangenome Reference Consortium, and the Telomere-to-Telomere Consortium.

Recent Publications

• De novo assembly of 64 haplotype-resolved human genomes of diverse ancestry and integrated analysis of structural variation
  in press (preprint)
• Fully phased human genome assembly without parental data using single-cell strand sequencing and long reads.
  Porubsky, D. et al.
  Nature Biotechnology (2020) doi:10.1038/s41587-020-0719-5
• Single-cell analysis of structural variations and complex rearrangements with tri-channel processing.
  Sanders, A. D. et al.
  Nature Biotechnology (2019) doi:10.1038/s41587-019-0366-x
• Recurrent inversion toggling and great ape genome evolution.
  Porubsky, D. et al.
  Nature Genetics 1–10 (2020) doi:10.1038/s41588-020-0646-x
• A diploid assembly-based benchmark for variants in the major histocompatibility complex.
  Chin, C.-S. et al.
  Nature Communications 11, 4794 (2020) doi:10.1038/s41467-020-18564-9