We are pleased to invite you to a special webinar organized within the FORGENOM II project, featuring Dr. Dávid Porubský, a leading researcher in the fields of bioinformatics and genomics.

👉 Link to join the webinar: https://meet.google.com/whm-omum-ofq

Speaker

Dr. Dávid Porubský is a Slovak-born bioinformatician and genomic researcher based at the Department of Genome Sciences at the University of Washington in Seattle, where he holds the position of Acting Instructor in the laboratory of Professor Evan E. Eichler. Since early 2025, he has also been a member of the research staff at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, further strengthening his ties to the European research landscape.

He earned his PhD in Bioinformatics from the University of Groningen in the Netherlands, focusing on haplotype-resolved genomes and their computational challenges. He previously completed both his Bachelor’s and Master’s degrees in Molecular Biology at Comenius University in Bratislava and has held research positions across Europe and North America. His research bridges cutting-edge genomic technologies and computational biology, with a focus on human genome assembly, structural variation, and single-cell sequencing. He has been the first author or a co-author of numerous high-impact publications in Nature, Science, Nature Genetics, and Nature Biotechnology, and is widely recognized as a leading expert in the study of human genetic variation and genome architecture.

Abstract

Telomere-to-telomere (T2T) chromosome assemblies generated from diploid samples provide access to complete genetic information, allowing us to revisit fundamental properties of mutation, transmission, and genetic recombination. We have generated deep Pacific Biosciences (PacBio) high-fidelity (HiFi), ultra-long Oxford Nanopore Technologies (ONT), Strand-seq, and Illumina whole-genome sequencing data to construct near-T2T, phased genome assemblies from primary material obtained from a 4-generation (G1-G4), 28-member CEPH reference family (1463). Using a hybrid genome assembly pipeline, we created reference genome-grade assemblies that are highly accurate (QV>50) and contiguous (N50 >100 Mbp), resolving both the paternal and maternal haplotypes, including complete centromeres and complex regions of segmental duplications (SDs). We constructed a comprehensive and validated catalog of single-nucleotide variants, indels, short tandem repeats, and structural variants for each haplotype from each member and assessing transmission characteristics, including a detailed assessment of inversion polymorphisms. We estimate 98-206 de novo mutations per transmission and show that centromeres are remarkably stable when transmitted from generation to generation. We also document the first de novo structural mutation of centromeres, consistent with higher-order repeat (HOR)-mediated changes of α-satellite DNA. The use of multiple orthogonal technologies, near-T2T phased-genome assemblies, and a multi-generation family to assess transmission as well epigenetic changes has the potential to create a “truth set” for all classes of human genetic variation upon which to test and benchmark new technologies.