Olanrewaju Austine-Orimoloye

Ensembl (https://www.ensembl.org) is unique in its flexible infrastructure for access to genomic data and annotation. It has been designed to efficiently deliver annotation at scale for all eukaryotic life, and it also provides deep comprehensive annotation for key species. Genomes representing a greater diversity of species are increasingly being sequenced. In response, we have focussed our recent efforts on expediting the annotation of new assemblies. Here, we report the release of the greatest annual number of newly annotated genomes in the history of Ensembl via our dedicated Ensembl Rapid Release platform (http://rapid.ensembl.org). We have also developed a new method to generate comparative analyses at scale for these assemblies and, for the first time, we have annotated non-vertebrate eukaryotes. Meanwhile, we continually improve, extend and update the annotation for our high-value reference vertebrate genomes and report the details here. We have a range of specific software tools for specific tasks, such as the Ensembl Variant Effect Predictor (VEP) and the newly developed interface for the Variant Recoder. All Ensembl data, software and tools are freely available for download and are accessible programmatically.

Ensembl (https://www.ensembl.org) has produced high-quality genomic resources for vertebrates and model organisms for more than twenty years. During that time, our resources, services and tools have continually evolved in line with both the publicly available genome data and the downstream research and applications that utilise the Ensembl platform. In recent years we have witnessed a dramatic shift in the genomic landscape. There has been a large increase in the number of high-quality reference genomes through global biodiversity initiatives. In parallel, there have been major advances towards pangenome representations of higher species, where many alternative genome assemblies representing different breeds, cultivars, strains and haplotypes are now available. In order to support these efforts and accelerate downstream research, it is our goal at Ensembl to create high-quality annotations, tools and services for species across the tree of life. Here, we report our resources for popular reference genomes, the dramatic growth of our annotations (including haplotypes from the first human pangenome graphs), updates to the Ensembl Variant Effect Predictor (VEP), interactive protein structure predictions from AlphaFold DB, and the beta release of our new website.

Ensembl (https://www.ensembl.org) is a freely available genomic resource that has produced high-quality annotations, tools, and services for vertebrates and model organisms for more than two decades. In recent years, there has been a dramatic shift in the genomic landscape, with a large increase in the number and phylogenetic breadth of high-quality reference genomes, alongside major advances in the pan-genome representations of higher species. In order to support these efforts and accelerate downstream research, Ensembl continues to focus on scaling for the rapid annotation of new genome assemblies, developing new methods for comparative analysis, and expanding the depth and quality of our genome annotations. This year we have continued our expansion to support global biodiversity research, doubling the number of annotated genomes we support on our Rapid Release site to over 1700, driven by our close collaboration with biodiversity projects such as Darwin Tree of Life. We have also strengthened support for key agricultural species, including the first regulatory builds for farmed animals, and have updated key tools and resources that support the global scientific community, notably the Ensembl Variant Effect Predictor. Ensembl data, software, and tools are freely available.

Ensembl (www.ensembl.org) is an open platform integrating publicly available genomics data across the tree of life with a focus on eukaryotic species related to human health, agriculture and biodiversity. This year has seen a continued expansion in the number of species represented, with >4800 eukaryotic and >31 300 prokaryotic genomes available. The new Ensembl site, currently in beta, has continued to develop, currently holding >2700 eukaryotic genome assemblies. The new site provides genome, gene, transcript, homology and variation views, and will replace the current Rapid Release site; this represents a key step towards provision of a single integrated Ensembl site. Additional activities have included developing improved regulatory annotation for human, mouse and agricultural species, and expanding the Ensembl Variant Effect Predictor tool. To learn more about Ensembl, help and documentation are available along with an extensive training program that can be accessed via our training pages.

Abstract Diverse sets of complete human genomes are required to construct a pangenome reference and to understand the extent of complex structural variation. Here we sequence 65 diverse human genomes and build 130 haplotype-resolved assemblies (median continuity of 130 Mb), closing 92% of all previous assembly gaps 1,2 and reaching telomere-to-telomere status for 39% of the chromosomes. We highlight complete sequence continuity of complex loci, including the major histocompatibility complex (MHC), SMN1 / SMN2 , NBPF8 and AMY1/AMY2 , and fully resolve 1,852 complex structural variants. In addition, we completely assemble and validate 1,246 human centromeres. We find up to 30-fold variation in α-satellite higher-order repeat array length and characterize the pattern of mobile element insertions into α-satellite higher-order repeat arrays. Although most centromeres predict a single site of kinetochore attachment, epigenetic analysis suggests the presence of two hypomethylated regions for 7% of centromeres. Combining our data with the draft pangenome reference 1 significantly enhances genotyping accuracy from short-read data, enabling whole-genome inference 3 to a median quality value of 45. Using this approach, 26,115 structural variants per individual are detected, substantially increasing the number of structural variants now amenable to downstream disease association studies.