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Comprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE1and RefSeq2launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins. Here, we describe the MANE transcript sets for use as universal standards for variant reporting and browser display. The MANE Select set identifies a representative transcript for each human protein-coding gene, whereas the MANE Plus Clinical set provides additional transcripts at loci where the Select transcripts alone are not sufficient to report all currently known clinical variants. Each MANE transcript represents an exact match between the exonic sequences of an Ensembl/GENCODE transcript and its counterpart in RefSeq such that the identifiers can be used synonymously. We have now released MANE Select transcripts for 97% of human protein-coding genes, including all American College of Medical Genetics and Genomics Secondary Findings list v3.0 (ref.3) genes. MANE transcripts are accessible from major genome browsers and key resources. Widespread adoption of these transcript sets will increase the consistency of reporting, facilitate the exchange of data regardless of the annotation source and help to streamline clinical interpretation.

The Dog Aging Project is a long-term longitudinal study of ageing in tens of thousands of companion dogs. The domestic dog is among the most variable mammal species in terms of morphology, behaviour, risk of age-related disease and life expectancy. Given that dogs share the human environment and have a sophisticated healthcare system but are much shorter-lived than people, they offer a unique opportunity to identify the genetic, environmental and lifestyle factors associated with healthy lifespan. To take advantage of this opportunity, the Dog Aging Project will collect extensive survey data, environmental information, electronic veterinary medical records, genome-wide sequence information, clinicopathology and molecular phenotypes derived from blood cells, plasma and faecal samples. Here, we describe the specific goals and design of the Dog Aging Project and discuss the potential for this open-data, community science study to greatly enhance understanding of ageing in a genetically variable, socially relevant species living in a complex environment.

Cells contain hundreds of organelles and macromolecular assemblies. Obtaining a complete understanding of their intricate organization requires the nanometre-level, three-dimensional reconstruction of whole cells, which is only feasible with robust and scalable automatic methods. Here, to support the development of such methods, we annotated up to 35 different cellular organelle classes—ranging from endoplasmic reticulum to microtubules to ribosomes—in diverse sample volumes from multiple cell types imaged at a near-isotropic resolution of 4 nm per voxel with focused ion beam scanning electron microscopy (FIB-SEM)1. We trained deep learning architectures to segment these structures in 4 nm and 8 nm per voxel FIB-SEM volumes, validated their performance and showed that automatic reconstructions can be used to directly quantify previously inaccessible metrics including spatial interactions between cellular components. We also show that such reconstructions can be used to automatically register light and electron microscopy images for correlative studies. We have created an open data and open-source web repository, ‘OpenOrganelle’, to share the data, computer code and trained models, which will enable scientists everywhere to query and further improve automatic reconstruction of these datasets. Focused ion beam scanning electron microscopy (FIB-SEM) combined with deep-learning-based segmentation is used to produce three-dimensional reconstructions of complete cells and tissues, in which up to 35 different organelle classes are annotated.

Data sharing was a core principle that led to the success of the Human Genome Project 20 years ago. Now scientists are struggling to keep information free. Data sharing was a core principle that led to the success of the Human Genome Project 20 years ago. Now scientists are struggling to keep information free.

Digitized patient charts were supposed to revolutionize medical practice. Artificial intelligence could help unlock their potential. Digitized patient charts were supposed to revolutionize medical practice. Artificial intelligence could help unlock their potential.

How did data get so big? Through political, social and economic interests, shows Sabina Leonelli, in the fourth essay on how the past 150 years have shaped the science system, marking Nature’s anniversary. How did data get so big? Through political, social and economic interests, shows Sabina Leonelli.

Metastatic cancer is a major cause of death and is associated with poor treatment efficacy. A better understanding of the characteristics of late-stage cancer is required to help adapt personalized treatments, reduce overtreatment and improve outcomes. Here we describe the largest, to our knowledge, pan-cancer study of metastatic solid tumour genomes, including whole-genome sequencing data for 2,520 pairs of tumour and normal tissue, analysed at median depths of 106× and 38×, respectively, and surveying more than 70 million somatic variants. The characteristic mutations of metastatic lesions varied widely, with mutations that reflect those of the primary tumour types, and with high rates of whole-genome duplication events (56%). Individual metastatic lesions were relatively homogeneous, with the vast majority (96%) of driver mutations being clonal and up to 80% of tumour-suppressor genes being inactivated bi-allelically by different mutational mechanisms. Although metastatic tumour genomes showed similar mutational landscape and driver genes to primary tumours, we find characteristics that could contribute to responsiveness to therapy or resistance in individual patients. We implement an approach for the review of clinically relevant associations and their potential for actionability. For 62% of patients, we identify genetic variants that may be used to stratify patients towards therapies that either have been approved or are in clinical trials. This demonstrates the importance of comprehensive genomic tumour profiling for precision medicine in cancer., The mutational landscape of metastatic cancer genomes is analysed in a large-scale, pan-cancer study of metastatic solid tumours that includes whole-genome sequencing of 2,520 tumour–normal tissue pairs.

International agencies need the mandate, funds and expertise to connect information — otherwise pandemics, hunger and unsustainability will go unsolved. International agencies need the mandate, funds and expertise to connect information — otherwise pandemics, hunger and unsustainability will go unsolved.

Researchers warn that plans to prevent the next global outbreak don’t consider the failures that have fuelled our current predicament. Researchers warn that plans to prevent the next global outbreak don’t consider the failures that have fuelled our current predicament.

The head of scientific work at the World Health Organization reflects on the agency’s challenges and achievements as it navigates the COVID pandemic. The head of scientific work at the World Health Organization reflects on the agency’s challenges and achievements as it navigates the COVID pandemic.

Researchers have spoken out against policies that have exacerbated the country’s coronavirus crisis. Policymakers must listen. Researchers have spoken out against policies that have exacerbated the country’s coronavirus crisis. Policymakers must listen.

Efforts to protect people’s privacy in a massive international cancer project offer lessons for data sharing. Efforts to protect people’s privacy in a massive international cancer project offer lessons for data sharing.

Social networking tools, opportunities to share resources and creatively capitalizing on regional differences can give researchers an edge. Social networking tools, opportunities to share resources and creatively capitalizing on regional differences can give researchers an edge.

Palaeontologists have been urged to share 3D scans of fossils online, but a Nature analysis finds that few researchers do so. Palaeontologists have been urged to share 3D scans of fossils online, but a Nature analysis finds that few researchers do so.