Comment in 2024

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.