An international team of researchers have significantly expanded the catalogue of known human genetic variation. The resulting datasets, shared in two back-to-back publications in the journal Nature, constitute what may be the most complete overview of the human genome to date. In tests, the new reference set reduces the list of suspect mutations from tens of thousands to just a few hundred, accelerating the path to the diagnosis of rare genetic syndromes and other types of diseases like cancer. The two papers provide a roadmap that makes assembling a complete human pangenome more practical rather than aspirational.

The 1000 Genomes Project (2007–2015) collected DNA samples from diverse human populations across five continents to analyse genetic variation from humans across the globe. Using advanced sequencing technologies, scientists have now mapped genomic variation in over 1,000 individuals from the project, offering new insights into human biology. In a complementary study, researchers assembled nearly complete genome sequences for 65 individuals, enabling detailed analyses of complex regions such as centromeres. These new datasets represent one of the most comprehensive overviews of the human genome to date and will enhance our understanding of genetic diversity across populations. Structural variations mapped through these datasets play a major role in many diseases, including cancer, providing a reference to allow understanding of what goes wrong under disease conditions in future clinical studies.

Pancreatic cancer cachexia is a devastating syndrome marked by unintentional weight loss, skeletal muscle wasting, and metabolic dysfunction that severely impairs patient outcomes. Affecting over 60% of pancreatic cancer patients, cachexia contributes to reduced quality of life, therapy intolerance, and high mortality. In a new comprehensive review published in hLife, researchers from the Peking Union Medical College Hospital and Harvard T.H. Chan School of Public Health highlight how this condition arises not from malnutrition alone, but through complex systemic crosstalk among multiple organs. The review provides a detailed account of the biological drivers of cachexia—including inflammatory cytokines, TGF-β family ligands, catabolic mediators, and tumor-derived extracellular vesicles—and their roles in orchestrating multi-organ deterioration. It also explores cutting-edge animal models and proposes potential therapeutic targets that could disrupt the vicious cycle of body wasting. This work lays a foundation for future clinical strategies to diagnose, monitor, and treat cachexia as a systemic disease.