Alla Mikheenko

Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion-base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies.

Motivation: The emergence of high-throughput sequencing technologies revolutionized genomics in early 2000s. The next revolution came with the era of long-read sequencing. These technological advances along with novel computational approaches became the next step towards the automatic pipelines capable to assemble nearly complete mammalian-size genomes. Results: In this manuscript, we demonstrate performance of the state-of-the-art genome assembly software on six eukaryotic datasets sequenced using different technologies. To evaluate the results, we developed QUAST-LG-a tool that compares large genomic de novo assemblies against reference sequences and computes relevant quality metrics. Since genomes generally cannot be reconstructed completely due to complex repeat patterns and low coverage regions, we introduce a concept of upper bound assembly for a given genome and set of reads, and compute theoretical limits on assembly correctness and completeness. Using QUAST-LG, we show how close the assemblies are to the theoretical optimum, and how far this optimum is from the finished reference. Availability and implementation: http://cab.spbu.ru/software/quast-lg. Supplementary information: Supplementary data are available at Bioinformatics online.

UNLABELLED: During the past years we have witnessed the rapid development of new metagenome assembly methods. Although there are many benchmark utilities designed for single-genome assemblies, there is no well-recognized evaluation and comparison tool for metagenomic-specific analogues. In this article, we present MetaQUAST, a modification of QUAST, the state-of-the-art tool for genome assembly evaluation based on alignment of contigs to a reference. MetaQUAST addresses such metagenome datasets features as (i) unknown species content by detecting and downloading reference sequences, (ii) huge diversity by giving comprehensive reports for multiple genomes and (iii) presence of highly relative species by detecting chimeric contigs. We demonstrate MetaQUAST performance by comparing several leading assemblers on one simulated and two real datasets. AVAILABILITY AND IMPLEMENTATION: http://bioinf.spbau.ru/metaquast CONTACT: aleksey.gurevich@spbu.ru SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, and functions, which include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere human genome assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric and centromeric repeats, which constitute 6.2% of the genome (189.9 megabases). Detailed maps of these regions revealed multimegabase structural rearrangements, including in active centromeric repeat arrays. Analysis of centromere-associated sequences uncovered a strong relationship between the position of the centromere and the evolution of the surrounding DNA through layered repeat expansions. Furthermore, comparisons of chromosome X centromeres across a diverse panel of individuals illuminated high degrees of structural, epigenetic, and sequence variation in these complex and rapidly evolving regions.