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Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

An inactive mutant of a bacterial O-GlcNAc hydrolase was used as an affinity reagent to enrich O-GlcNAc-modified proteins from Drosophila embryos and led to the identification, by MS–proteomics, of O-GlcNAcylated proteins involved in embryogenesis.

An early step in the autophagy process is the conjugation of the ubiquitin-like proteins (UBLs) Atg8 and Atg12 to their targets. Structural and functional experiments reveal how the autophagy E1 Atg7 uses a trans mechanism to catalyze the charging of the autophagy UBLs onto their respective carrier E2 proteins, Atg3 and Atg10.

A state-dependent dopamine filter system in the male Drosophila brain balances threat perception against the drive to mate.

Transgenic RNA ‘sponges’ that inhibit specific microRNAs are valuable tools for functional studies. Fulga et al. present a library of conditional microRNA sponges in Drosophila, and reveal widespread involvement of microRNAs in the maintenance of adult muscle structure and function.

High data volumes from multidimensional imaging techniques can lead to slow collection and processing times. Here, the authors implement multispectral fluorescence lifetime imaging microscopy (FLIM) that uses time-correlated photon counting technology to reach simultaneously high imaging rates combined with high spectral and temporal resolution.

Using avian trait data and genomic data, the authors infer whether changes in net effective population size over time in response to climate change are correlated with multiple morphological and life history traits; they find that larger-bodied, slower-reproducing species with limited dispersal capacity are most sensitive to changes in warming and cooling climates.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

DNA methylation profiles from 26 bat species accurately predicts chronological age, while longevity-related methylation patterns across the genome suggest that bat longevity results from augmented immune response and cancer suppression.

The cryo-EM structure of phage φTE is presented, revealing a distinct neck topology, tail sheath baseplate organization and oligomeric state of the tape measure protein. These features suggest a mechanism linking base plate conformational changes to sheath contraction and genome ejection.

A Homo aff. erectus individual dated to 1.4 million to 1.1 million years ago found at Sima del Elefante (Sierra de Atapuerca, Spain) does not display the modern-human-like aspect of Homo antecessor found at the neighbouring Gran Dolina site (900,000–800,000 years ago).

The GntR superfamily is one of the largest families of transcription factors in prokaryotes. Here the authors combine biophysical analysis and structural biology to dissect the mechanism by which NanR — a GntR-family regulator — binds to its promoter to repress the transcription of genes necessary for sialic acid metabolism.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Daedalus is looking to the structure of birds' wings to develop aircraft wings with minimal drag and optimal lift.

Small populations of interneurons in mice and inDrosophila melanogasterhave been shown to control both mating and aggression. Here, David Anderson proposes that these neuron populations may represent a conserved or analogous circuit node that controls reproductive behaviours in animals by promoting internal motivational, arousal or drive states.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

The bird hand is thought to derive from the second, third and fourth digits of an ancestral five-digit hand. However, the three-fingered hand of theropod dinosaurs, which are the closest extinct relatives of birds, are thought to derive from the first, second and third digits. The discovery of a small, primitive herbivorous theropod from the Jurassic period of China with a stub of the first digit alongside more developed second, third and fourth digits, sheds light on this problem.

The authors find that the gustatory pheromone detection system in Drosophila can control male-male aggression and that it acts independently of the olfactory pheromone detection system to modulate both aggression and courtship behaviors.

Early Eocene ENSO had stronger amplitude and longer periodicity than present, driven primarily by tectonic changes, but high atmospheric CO₂ levels offset tectonic influence on the ENSO amplitude through altered ocean-atmospheric interaction.

Ongoing hydrogen loss from two sibling exoplanets provides support for the role of such hydrogen loss in the evolution of close-orbiting sub-Neptunes.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Lokareddy et al. determine the complete structure of DEV, a lytic virus that infects Pseudomonas aeruginosa, using a combination of cryo-electron microscopy, biochemical methods, and genetic knockouts. They propose that the virion-associated RNA polymerase may be part of a genome ejection motor.

Although aggression is known to be regulated by pheromones in many animal species, in no system have the pheromones, their receptors and corresponding sensory neurons been identified. Here, 11-cis-vaccenyl acetate (cVA), a volatile pheromone produced by male fruitflies, is shown to promote male-to-male aggression through the activation of olfactory sensory neurons expressing the receptor Or67d.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Some cancer patients first present with metastases where the ___location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.