The complete sequence of a human Y chromosome.

The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure that includes long palindromes, tandem repeats and segmental duplications. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, showing the complete ampliconic structures of gene families TSPY, DAZ and RBMY; 41 additional protein-coding genes, mostly from the TSPY family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region.

UniAligner: a parameter-free framework for fast sequence alignment.

Even though the recent advances in 'complete genomics' revealed the previously inaccessible genomic regions, analysis of variations in centromeres and other extra-long tandem repeats (ETRs) faces an algorithmic challenge since there are currently no tools for accurate sequence comparison of ETRs. Counterintuitively, the classical alignment approaches, such as the Smith-Waterman algorithm, fail to construct biologically adequate alignments of ETRs. We present UniAligner-the parameter-free sequence alignment algorithm with sequence-dependent alignment scoring that automatically changes for any pair of compared sequences.

A scalable model for simulating multi-round antibody evolution and benchmarking of clonal tree reconstruction methods.

Affinity maturation (AM) of B cells through somatic hypermutations (SHMs) enables the immune system to evolve to recognize diverse pathogens. The accumulation of SHMs leads to the formation of clonal lineages of antibody-secreting b cells that have evolved from a common naïve B cell. Advances in high-throughput sequencing have enabled deep scans of B cell receptor repertoires, paving the way for reconstructing clonal trees.

Fast and accurate mapping of long reads to complete genome assemblies with VerityMap.

Recent advancements in long-read sequencing have enabled the telomere-to-telomere (complete) assembly of a human genome and are now contributing to the haplotype-resolved complete assemblies of multiple human genomes. Because the accuracy of read mapping tools deteriorates in highly repetitive regions, there is a need to develop accurate, (detecting potential assembly errors), and e (distinguishing different haplotypes) tools for read mapping in complete assemblies. We describe the first accurate, error-exposing, and partially diploid-aware VerityMap tool for long-read mapping to complete assemblies.

Automated annotation of human centromeres with HORmon.

Recent advances in long-read sequencing opened a possibility to address the long-standing questions about the architecture and evolution of human centromeres. They also emphasized the need for centromere annotation (partitioning human centromeres into monomers and higher-order repeats [HORs]). Although there was a half-century-long series of semi-manual studies of centromere architecture, a rigorous centromere annotation algorithm is still lacking.

Chasing perfection: validation and polishing strategies for telomere-to-telomere genome assemblies.

Advances in long-read sequencing technologies and genome assembly methods have enabled the recent completion of the first telomere-to-telomere human genome assembly, which resolves complex segmental duplications and large tandem repeats, including centromeric satellite arrays in a complete hydatidiform mole (CHM13). Although derived from highly accurate sequences, evaluation revealed evidence of small errors and structural misassemblies in the initial draft assembly. To correct these errors, we designed a new repeat-aware polishing strategy that made accurate assembly corrections in large repeats without overcorrection, ultimately fixing 51% of the existing errors and improving the assembly quality value from 70.

The complete sequence of a human genome.

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.

Complete genomic and epigenetic maps of human centromeres.

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.

Multiplex de Bruijn graphs enable genome assembly from long, high-fidelity reads.

Although most existing genome assemblers are based on de Bruijn graphs, the construction of these graphs for large genomes and large k-mer sizes has remained elusive. This algorithmic challenge has become particularly pressing with the emergence of long, high-fidelity (HiFi) reads that have been recently used to generate a semi-manual telomere-to-telomere assembly of the human genome. To enable automated assemblies of long, HiFi reads, we present the La Jolla Assembler (LJA), a fast algorithm using the Bloom filter, sparse de Bruijn graphs and disjointig generation.

CentromereArchitect: inference and analysis of the architecture of centromeres.

Motivation: Recent advances in long-read sequencing technologies led to rapid progress in centromere assembly in the last year and, for the first time, opened a possibility to address the long-standing questions about the architecture and evolution of human centromeres. However, since these advances have not been yet accompanied by the development of the centromere-specific bioinformatics algorithms, even the fundamental questions (e.g.

The structure, function and evolution of a complete human chromosome 8.

The complete assembly of each human chromosome is essential for understanding human biology and evolution. Here we use complementary long-read sequencing technologies to complete the linear assembly of human chromosome 8. Our assembly resolves the sequence of five previously long-standing gaps, including a 2.

Automated assembly of centromeres from ultra-long error-prone reads.

Centromeric variation has been linked to cancer and infertility, but centromere sequences contain multiple tandem repeats and can only be assembled manually from long error-prone reads. Here we describe the centroFlye algorithm for centromere assembly using long error-prone reads, and apply it to assemble human centromeres on chromosomes 6 and X. Our analyses reveal putative breakpoints in the manual reconstruction of the human X centromere, demonstrate that human X chromosome is partitioned into repeat subfamilies and provide initial insights into centromere evolution.

Telomere-to-telomere assembly of a complete human X chromosome.

After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end to end, and hundreds of unresolved gaps persist. Here we present a human genome assembly that surpasses the continuity of GRCh38, along with a gapless, telomere-to-telomere assembly of a human chromosome.

The string decomposition problem and its applications to centromere analysis and assembly.

Motivation: Recent attempts to assemble extra-long tandem repeats (such as centromeres) faced the challenge of translating long error-prone reads from the nucleotide alphabet into the alphabet of repeat units. Human centromeres represent a particularly complex type of high-order repeats (HORs) formed by chromosome-specific monomers. Given a set of all human monomers, translating a read from a centromere into the monomer alphabet is modeled as the String Decomposition Problem.

TandemTools: mapping long reads and assessing/improving assembly quality in extra-long tandem repeats.

Motivation: Extra-long tandem repeats (ETRs) are widespread in eukaryotic genomes and play an important role in fundamental cellular processes, such as chromosome segregation. Although emerging long-read technologies have enabled ETR assemblies, the accuracy of such assemblies is difficult to evaluate since there are no tools for their quality assessment. Moreover, since the mapping of error-prone reads to ETRs remains an open problem, it is not clear how to polish draft ETR assemblies.

Reconstructing Antibody Repertoires from Error-Prone Immunosequencing Reads.

Transforming error-prone immunosequencing datasets into Ab repertoires is a fundamental problem in immunogenomics, and a prerequisite for studies of immune responses. Although various repertoire reconstruction algorithms were released in the last 3 y, it remains unclear how to benchmark them and how to assess the accuracy of the reconstructed repertoires. We describe an accurate IgReC algorithm for constructing Ab repertoires from high-throughput immunosequencing datasets and a new framework for assessing the quality of reconstructed repertoires.