Telomere-to-Telomere: the complete human genome

Nature Methods is pleased to publish several papers presenting methods developed by members of the Telomere-to-Telomere (T2T) Consortium, which facilitated the generation and analysis of the first complete human genome.

An optimized pipeline for improved inference and analysis of structural variants (SVs) has been developed, which uses Iris for refining breakpoints and sequences, and Jasmine for comparing SV calls at population scale.

The work describes the validation and polishing strategies developed by the telomere-to-telomere consortium for evaluating and improving the first complete human genome assembly.

Merfin is a computational tool for variant filtering that improves accuracy in genotyping and genome assembly polishing.

Winnowmap2 enables better long-read mapping and more accurate variant calling in repetitive regions of the genome.

DiMeLo-seq uses native long-read sequencing to examine protein–DNA interactions by mapping exogenous methylation marks generated by a nonspecific DNA methyltransferase, as well as profile endogenous CpG methylation simultaneously.

The complete assembly of human chromosome 8 resolves previous gaps and reveals hidden complex forms of genetic variation, enabling functional and evolutionary characterization of primate centromeres.

High-coverage, ultra-long-read nanopore sequencing is used to create a new human genome assembly that improves on the coverage and accuracy of the current reference (GRCh38) and includes the gap-free, telomere-to-telomere sequence of the X chromosome.

The release of the first telomere-to-telomere (T2T) human genome sequence marks a milestone for human genomics research and holds promise of complete genomes for evolutionary genomic studies. Here we describe the advances that this new human genome assembly represents and explore the potential insights that the complete genome sequence could bring to evolutionary genomics. We also discuss the potential challenges to be faced in applying this new sequencing strategy to a broad spectrum of extant species.

Sequences of the human genome have typically included gaps in repetitive regions of DNA. A combination of state-of-the-art technologies has now enabled researchers to generate the first complete human genome sequence.

A repeat-aware pipeline corrects structural assembly errors and polishes assembly sequences in large repeats without overcorrection.

DiMeLo-seq leverages immunotethered DNA methyltransferases with long-read sequencing to map the locations of chromatin proteins in their natural context.

Researchers added 200 million DNA base pairs and 115 protein-coding genes — but they’ve yet to entirely sequence the Y chromosome.

Advances in sequencing technology mean that scientists are on the verge of finally finishing an end-to-end human genome map.

Genome assembly projects get a boost from high-accuracy long-read sequencing.