Nature Genetics

Hematotoxicity: the hidden legacy of CAR T cell therapy

2026-11-03

Nature Genetics, Published online: 03 November 2026; doi:10.1038/s41588-026-02805-6

CD19-directed chimeric antigen receptor (CAR) T cell therapy can produce durable remission in patients with lymphoma, but persistent hematological toxicities remain poorly understood. We show that clonal expansion of mutated hematopoietic clones (clonal hematopoiesis) in an inflamed bone marrow environment is linked to prolonged cytopenias, impaired immune recovery and treatment-related myeloid malignancies.

Progress and disparities in fungal genomics in the long-read era

Erika Kroll — 2026-11-03

Nature Genetics, Published online: 03 November 2026; doi:10.1038/s41588-026-02790-w

This study examines how long-read sequencing has transformed fungal genome assemblies and uncovered genome features once hidden in fragmented drafts, while also revealing that taxonomic bias and uneven annotation continue to constrain the field.

A framework for genome-wide characterization of DNA methylation and variant effect prediction

Weiguang Mao — 2026-11-03

Nature Genetics, Published online: 03 November 2026; doi:10.1038/s41588-026-02807-4

This study introduces a framework for integrating DNA methylation data across more than 90 tissues and cell types, characterizing genome-wide methylation patterns and predicting context-specific effects of genetic variants on DNA methylation and regulatory function using a deep learning model, Wreath.

AI-based precision prognostics and therapy personalization for childhood brain tumors

Sabina Stefan — 2026-11-03

Nature Genetics, Published online: 03 November 2026; doi:10.1038/s41588-026-02815-4

Stefan et al. present MANTIS, an AI model to predict individualized survival in childhood brain tumors from routine DNA methylation profiling. MANTIS may help identify patients who benefit from less intense treatment to reduce lifelong side effects.

Clonal hematopoiesis and cytopenias following CAR19 therapy

Mark P. Hamilton — 2026-11-02

Nature Genetics, Published online: 02 November 2026; doi:10.1038/s41588-026-02795-5

This study shows that clonal hematopoiesis expands after chimeric antigen receptor (CAR) T cell therapy and contributes to secondary myeloid cancers. In addition, the CAR vector frequently integrates into pre-existing clonal hematopoiesis.

A catalog of transcriptome genetic regulation in a consanguineous Middle Eastern biobank

Haroon Naeem — 2026-11-02

Nature Genetics, Published online: 02 November 2026; doi:10.1038/s41588-026-02785-7

This study reports an atlas of transcriptomic genetic effects from a Middle Eastern population biobank, revealing population-specific regulatory variants and links to clinically relevant traits.

Ethical challenges in patient-focused drug development for rare genetic diseases

Meghan C. Halley — 2026-10-30

Nature Genetics, Published online: 30 October 2026; doi:10.1038/s41588-026-02824-3

Patient and family groups increasingly drive the development of drugs for rare diseases, from trial design to regulatory strategy. This model of patient-focused drug development can accelerate therapies for rare diseases but also generates recurring ethical tensions with academic, industry and regulatory partners that remain underdiscussed.

A haplotype reference panel constructed from 490,319 UK Biobank genomes improves genotype imputation for global populations

Lars Wienbrandt — 2026-10-30

Nature Genetics, Published online: 30 October 2026; doi:10.1038/s41588-026-02819-0

A haplotype reference panel constructed from whole-genome sequencing data from 490,319 UK Biobank participants improves genotype imputation accuracy across diverse populations and achieves lower phasing switch error rates than existing approaches.