Volume 51 Issue 6, June 2019

The Nordic region, comprising primarily Denmark, Estonia, Finland, Iceland, Norway and Sweden, has many of the necessary characteristics for being at the forefront of genome-based precision medicine. These include egalitarian and universal healthcare, expertly curated patient and population registries, biobanks, large population-based prospective cohorts linked to registries and biobanks, and a widely embraced sense of social responsibility that motivates public engagement in biomedical research. However, genome-based precision medicine can be achieved only through coordinated action involving all actors in the healthcare sector. Now is an opportune time to organize scientists in the Nordic region, together with other stakeholders including patient representatives, governments, pharmaceutical companies, academic institutions and funding agencies, to initiate a Nordic Precision Medicine Initiative. We present a roadmap for how this organization can be created. The Initiative should facilitate research, clinical trials and knowledge transfer to meet regional and global health challenges.

Epigenetic heterogeneity underlies the diversity of cell states found in health and disease. A new study presents a method for profiling of histone modifications in single cells and applies it to identify rare chromatin states, possibly predisposed to drug resistance, within patient-derived tumor xenografts.

Multi-tissue transcriptome analyses using PrediXcan identify numerous trait-associated genes for schizophrenia, bipolar disorder, attention deficit hyperactivity disorder and broad depression, and highlight potentially causal genes in non-brain tissues.

Phosphorylation of histone H3.3 at serine 31 by CHK1 is shown to stimulate activity of the acetyltransferase p300 in trans. Depletion of histone H3.3 in embryonic stem cells reduces enhancer acetylation during differentiation.

The authors generate Dux cluster knockout mouse lines and find that embryos can survive to adulthood. Transcriptome profiling of the mutant embryos indicates minimal effects on zygotic genome activation.

The authors present a new genomic prediction method for maize germplasm evaluation under genotype × environment interaction, in which genotype × environment interaction of grain yield components is modeled as genotypic sensitivity to environmental drivers.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

Application of a deep-learning-based framework shows that individuals with autism spectrum disorder (ASD) harbor regulation-disrupting mutations of higher functional impact than those in unaffected siblings and identifies a convergent genetic landscape of coding and noncoding de novo mutations in ASD.

Similarity regression is an improved method for predicting transcription factor motifs, enabling analysis of DNA-binding motifs across eukaryotes and an expansion of the Cis-BP database of measured and predicted transcription factor motifs.

The folate pathway enzyme MTHFD1 is recruited to chromatin by BRD4. Inhibition of BRD4 or MTHFD1 similarly changes nuclear metabolite composition and gene expression, and dual inhibition synergistically impairs cancer cell viability.

CRISPR screens identify JNK–JUN family genes as repressors of definitive endoderm differentiation in human pluripotent stem cells. JUN co-occupies stem cell enhancers with OCT4, NANOG, SMAD2 and SMAD3 and inhibits the exit from pluripotency.

Release of paused Pol II at specific intronic loci or chromatin domains favors the formation of abnormal DNA recombination, leading to cancer-associated chromosomal translocations.

Swapping the Xist/Tsix transcriptional units and placing their promoters in each other’s topologically associating domain shows that the topological partitioning of the X-inactivation center is critical to ensure proper X inactivation during development.

Analyses of 2,083 globally distributed group A Streptococcus (GAS) genomes enable the development of a compendium of all GAS vaccine antigen sequences, providing a platform for population-genomics-informed vaccine design.

A tomato pan-genome constructed from genome sequences of 725 tomato accessions captures 4,873 genes absent from the reference genome and identifies a rare allele of TomLoxC regulating fruit flavor.

A high-quality reference genome of the maize SK inbred line and analyses between the tropical SK line and two other maize genomes, B73 and Mo17, provide insights into structural variation and crop improvement.

The authors present a high-throughput single-cell ChIP-seq method with coverage of up to 10,000 loci per cell. They identify diverse chromatin landscapes in breast cancer cells characterized by dynamic H3K27me3 levels.