News & Comment

People with disabilities are under-represented in general (non-disability-specific) precision medicine research (PMR), limiting access to its benefits. We examine key reasons for this, focusing on the role of (dis)trust, and identify areas for further inquiry to guide researchers and enhance PMR’s trustworthiness for people with disabilities.

The rich ethnolinguistic and sociocultural differences that exist in India offers a unique opportunity to study human diversity. With the whole genomes of 10,000 healthy and unrelated Indians from 83 populations, the GenomeIndia project captures the genetic diversity of one of the highly underrepresented populations in the global genomics landscape.

In this era of rapidly expanding human genomics in research and healthcare, efficient data reuse is essential to maximize benefits for society. In response, the Federated European Genome–Phenome Archive (FEGA) was launched in 2022, and as of 2024, the FEGA network was composed of seven national nodes. Here we describe the complexities, challenges and achievements of FEGA, unravelling the dynamic interplay of regulatory frameworks, technical challenges and the shared vision of advancing genomic research.

This Comment outlines the creation of the Global Alliance for Spatial Technologies (GESTALT), a collaborative initiative aimed at fostering the growth and standardization of spatial tissue profiling technologies. It explores the need for GESTALT, its community-driven structure and its goals, spanning from the immediate to the long term.

Despite extensive advancements in cancer genetics in North America and Europe, the African continent remains underrepresented in this vital research area. Here we highlight a pioneering collaborative project in Kenya, with a focus on expanding cancer genetics services and research into retinoblastoma, a prototypical heritable cancer syndrome.

In the first-ever Undiagnosed Hackathon, nearly 100 experts from 28 countries combined advanced phenotyping and genomic techniques for 48 hours, ultimately providing diagnoses to 40% of the previously undiagnosed families. This inspiring model demonstrates the power of multidisciplinary collaboration and patient partnership in precision diagnostics.

Accurate naming of genetic variants is essential to identify clinical data that interpret the consequences of such variants. In partnership with the Human Genome Organization, we advocate for integration of VariantValidator in publishing of journals and databases, to improve the quality of shared genetic data and ultimately patient outcomes.

Polygenic scores (PGSs) have transformed human genetic research and have numerous potential clinical applications. Here we present a series of recent enhancements to the PGS Catalog and highlight the PGS Catalog Calculator, an open-source, scalable and portable pipeline for reproducibly calculating PGSs that democratizes equitable PGS applications.

R-loops contain DNA:RNA hybrids and an unpaired single-stranded DNA. N⁶-methyladenosine (m⁶A) has been reported to modulate R-loop levels, but with varying outcomes (R-loop resolution versus stabilization). We propose that in different contexts, m⁶A may either directly prevent R-loop accumulation or stabilize R-loops via the formation of RNA abasic sites.

Calls for more diverse data in genetics studies typically fall short of offering further guidance. Here we summarize a policy framework from the Global Alliance for Genomics and Health designed to fill this gap. The framework prompts researchers to consider both what types of diversity are needed and why, and how aims can be achieved through choices made throughout the data life cycle.

Genotype prediction from RNA sequencing (RNA-seq) data has become widespread, but there is a lack of clarity in current policy and inconsistency in data handling. To address this we call for a framework consisting of registered access for RNA-seq data, controlled access for genotypes, a code of conduct and enhanced downstream protections.

Efforts to integrate computational tools for variant effect prediction into the process of clinical decision-making are in progress. However, for such efforts to succeed and help to provide more informed clinical decisions, it is necessary to enhance transparency and address the current limitations of computational predictors.

Defining minimal standards for data collection is key to creating interoperative, searchable genomic and clinical databases. We highlight here the 1+Million Genomes Minimal Dataset for Cancer, encompassing 140 items in 8 domains to foster the collection of cancer data, inform transnational cooperation and advance precision cancer medicine.

The recently launched Egyptian Genome Project aims to sequence genomic variants of 100,000 apparently healthy Egyptian adults, with around 8,000 individuals suspected to have a genetic disease, as well as 200 ancient Egyptian mummies. The project will provide the first comprehensive genomic dataset from Egypt and North Africa.

Achieving a diagnosis for Indigenous people living with a rare, often genetic, disease is crucial for equitable healthcare. The International Rare Disease Research Consortium convened a global Task Force to bridge the gap in diagnosing Indigenous rare diseases, and identify solutions to tackle the health inequity faced by Indigenous people.

While the number of SARS-CoV-2 genome sequences grew to over 15 million, the Ultrafast Sample placement on Existing tRees (UShER) tool suite maintained a comprehensive phylogenetic tree in near real time. This experience, and critical performance improvements throughout the pandemic, provide valuable lessons for rapidly scaling analyses.

Keeping up with the latest variant-related research is vital for genomic medicine. Here we present LitVar 2.0, a significantly improved web-based system to accurately search for genetic variants in the unstructured literature. LitVar 2.0 provides a unified search of full text and supplementary data, and improved variant recognition accuracy.

Current ontologies of race, ethnicity and genetic ancestry rely on categorization, but have limitations — as exemplified by multiracial individuals. We argue that including these individuals will foster inclusion by better capturing complex identities, with equity benefits for the full human population.

The Qatar Genome Program was established to interrogate the genomics and genetics of populations in the Middle East. Improving precision medicine strategies and building long-term research capacity are both key aims of the initiative.