News & Views

Human centromeres contain a small chromatin region with low levels of DNA cytosine methylation that resides with CENP-A. Salinas-Luypaert et al. find a role of DNA methylation in maintaining the size and function of centromeres by controlling the binding affinity of key centromere components.

Bryophytes are a widespread group of land plants that occupy nearly all biomes, yet their genetics and evolutionary history have long remained underexplored. Now, a study that generates extensive genomic data for bryophytes highlights de novo gene formation and horizontal gene transfer as key forces that shape bryophyte diversity and adaptation.

A newly uncovered mechanism shows how a single transposable element of retroviral origin can adopt the expression pattern of a neighboring gene. This leads to the production of viral-like particles that disrupt organ formation when epigenetic silencing is compromised.

Two complementary studies used whole-genome sequencing of single cell-derived hematopoietic colonies to show that chemotherapy results in a marked decrease in hematopoietic stem and progenitor cell (HSPC) diversity, with the parallel evolution of multiple independent HSPCs harboring mutations in DNA damage response genes.

How primary gallbladder tumors evolve to acquire immunosuppressive and pro-metastatic capabilities remains unclear. A study using single-cell RNA sequencing coupled with spatial profiling and functional experiments has pinpointed mechanisms of immune-mediated tumor cell reprogramming, fostering disease progression.

Shigella is a major human pathogen with a stark lack of pipelines linking genome content to clinical pathogenesis. An innovative study using large-scale organoid models, combined with genome-wide mutagenesis screening, reveals virulence factors required for Shigella colonization.

Enhancer sequences evolve rapidly, which has led to the prevailing view that most are not functionally conserved across species. A study now challenges this assumption by leveraging interspecies point projection — a method that uses genome synteny to uncover hidden enhancer conservation.

CRISPR–Cas base editing of trinucleotide repeats shows promise in reducing somatic repeat expansions in Huntington’s disease and Friedreich’s ataxia, offering a potential new therapeutic strategy.

A large genome-wide meta-analysis across the allele frequency spectrum has identified genetic associations with infertility. This study reveals wide-ranging genetic insights underlying diagnostic heterogeneity in infertility.

Multivariate estimators of how much a perturbation affects the overall gene expression phenotype in Perturb-seq data can be derived using univariate statistics from differential gene expression tools.

In this study, somatic mutations in desmosome genes of keratinocytes were found to support melanoma growth. This work has fundamental implications for our understanding of the somatic landscape of cancer.

The biological significance of somatic mutations in rare genetic liver diseases has remained elusive. A study using genomic sequencing paired with experimental cell-based assays has shed light on the selective advantage and accumulation of somatic variants in SERPINA1 found in liver explants from patients with alpha-1 anti-trypsin deficiency.

Borzoi is a deep learning model that predicts RNA sequencing coverage across each exon of every human gene, across different cells and tissues, based on DNA sequence alone.

Mass spectrometry-based proteomics demonstrated its increasing analytical power and unique strengths in measuring genome-wide plasma proteomes and identifying protein quantitative trait loci (pQTLs), as reported in a study of over 3,000 Danish children and adolescents.

Cancer phylogenetic trees describe the evolutionary relationship between primary tumors and metastatic sites. A study now shows that mutations in guanine homopolymer microsatellites represent accurate molecular clocks, revealing the number of cell divisions that have occurred during cancer development and progression.

A study describes the development of PERFF-seq, a method to ‘FISH’ out rare cells using RNA markers, helping to solve the challenge in single-cell biology of studying cells that make up less than 1% of a sample.

A novel in vivo CRISPR screening platform identifies genetic modifiers of huntingtin CAG repeat somatic instability. These modifiers include known and novel genes that are promising therapeutic targets for Huntington’s disease.

PD-1 pathway blockade in combination with chemotherapy has emerged as a treatment paradigm for patients with resectable lung cancer, but insights into predictive biomarkers and mechanisms of immune responses are lacking. A study uses spatial transcriptomic methods to identify patterns within the tumor microenvironment associated with response.

Using reported parental disease history to decipher the genetics of Alzheimer’s disease may be promising, but this approach is also susceptible to complex selection and information bias that can mislead researchers if not accounted for.

A novel method for analyzing single-cell genomics enables direct inference of cell cycle and proliferation status, highlighting the diversity of proliferation rates in clonal cancer. This approach opens a new avenue for high-resolution exploration of the role of proliferation in cancer evolution at the single-cell level.