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Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

Molecular clock analyses calibrated with fossil material reveal a new timescale of early life.

Blatter’s radicals are highly valuable stable organic free radicals, comprising a heterocyclic ring system functionalized with a heteroaryl or alkyl group at the C-3 position. Here, the authors report a synthetic strategy to obtain Blatter’s radical substituted with an amine and amide group.

A study generates a clinicogenomics dataset resource, MSK-CHORD, that combines natural language processing-derived clinical annotations with patient medical data from various sources to improve models of cancer outcome.

Several cases of replicated radiations (in which sets of similar forms evolve repeatedly within different regions) have been described in animals. Here the authors provide a well-documented example in plants, specifically the Oreinotinus lineage within the angiosperm clade Viburnum in its spread from Mexico to Argentina through disjunct cloud forest environments.

Clark and colleagues show that plant anatomical diversity evolved episodically over geologic time, reflecting ecological expansion facilitated by reproductive innovations. This is paralleled in animals and fungi, suggesting a general evolutionary mode for multicellular bodyplans.

In a prospective international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy, ctDNA detection was associated with shorter survival, independently of clinicopathologic features and metabolic tumor volume.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

The activity of PD-1 blockade in patients with sarcoma has been modest so far. Here, the authors report the results of a pilot clinical trial to assess the efficacy and safety of bempegaldesleukin, a CD122-preferential interleukin-2 (IL-2) pathway agonist, in combination with the PD1 blockade (nivolumab) in patients with locally advanced or metastatic high-grade sarcoma.

 Malignant evolution enabled by p53 inactivation in mice proceeds through an ordered and predictable pattern of Trp53 loss of heterozygosity, accumulation of deletions, genome doubling and the emergence of gains and amplifications.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

Tuberculosis was once a major killer in Europe. Here the authors use metagenomics to obtain genomic sequences of Mycobacterium tuberculosisfrom human remains from eighteenth-century Hungary, revealing mixed infections within individuals as well as presence of the same strain in two individuals.

In a zebrafish model of human cutaneous and acral melanomas, CRKL amplification causes tumours to favour a fin ___location, indicating that tumour ___location is determined by both the driver oncogenes and the pre-existing positional identity gene program.

Mutations in BRCA1/2 are associated with a homologous recombination deficiency phenotype in BRCA-associated cancers. Reversion mutations can restore BRCA1/2 function and result in treatment resistance in these cancer-types. Here, the authors show that, in select cases, reversion mutations in BRCA1/2 can indicate prior BRCA-mediated tumorigenesis in non-canonical histologies.

How different oncogenic Akt mutants can affect the response to Akt inhibitors is currently unclear. Here, the authors analyse somatic mutations of Akt1-3 isoforms in several human cancers, investigate their oncogenic effects and therapeutic relevance in vitro and confirm some of their data in a clinical trial testing the AKT inhibitor capivasertib in patients with solid tumors harboring AKT alterations.

Heart failure is a complex syndrome that is associated with many different underlying risk factors. Here, to increase power, the authors jointly analyse cases of heart failure of different aetiologies in a genome-wide association study and identify 11 loci of which ten had not been previously reported.

DNA and RNA sequencing in large cohorts of patients with rectal cancer treated with neoadjuvant therapies identifies biomarkers of response that could inform patient selection for non-operative treatment strategies.

Subgenomic flavivirus RNAs are generated by a host exoribonuclease and play an important role in virus replication and pathogenesis. Here, the authors show the mechanism by which subgenomic flavivirus RNAs are generated and identify two structurally distinct sfRNA classes in flaviviruses.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

Pigeonpea is an important protein source in many developing countries, but limited genetic resources have constrained its improvement. The draft genome sequence of pigeonpea, the first for a nonindustrial crop and for a grain legume, should facilitate molecular breeding efforts to improve yields for subsistence farmers.

There are few available models to study neuroendocrine prostate cancer. Here they develop and characterize patient derived organoids from metastatic lesions, use these models to show the role of EZH2 in driving neuroendocrine phenotype, and perform high throughput organoid screening to identify therapeutic drug combinations.

Analysis of more than 17,000 tumours suggests that the contribution of germline and somatic mutations in the BRCA1 and BRCA2 genes to oncogenesis depends on tumour lineage.

The authors identify whole-genome doubling (WGD) in 30% of ~10,000 sequenced tumors from patients with advanced cancer. WGD correlates with increased risk of death across cancer types.

Molecular characterization of tumors informs clinical cancer care. Here, Taylor and colleagues review the progress, opportunities, and challenges of scientific and translational discovery that leverages prospective data from clinical genomic screening.