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The primitive hominins from Dmanisi in the Republic of Georgia are often thought to be akin to Homo erectus and are arguably the earliest known members of the human family outside Africa. This conclusion has come, so far, from the presentation of postcranial material: now a partial skeleton of an adolescent individual associated with a skull, and remains from three adult individuals, suggest that the Dmanisi hominids are even more primitive than that, akin to Homo habilis.

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.

Analysis of 2,170 SARS-CoV-2 sequences from the first wave of the COVID-19 epidemic in Spain provides insights into transmission patterns and the effects of lockdown on the emergence of new variants.

Here the authors report results from a randomized clinical trial testing a combination of ChAOx1/MVA.HTI vaccines and the TLR7 agonist vesatolimod in men living with HIV-1. While the treatment showed a good safety profile and induction of HTI-focused T-cell responses, viral rebound was similar in treatment arm and placebo arm.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

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.

Cavity optomechanics connects light to the mechanical degrees of freedom of a resonator and has great potential for sensing applications. Here, the authors realize a one-dimensional optomechanical crystal with a complete phononic bandgap containing high Q-factor modes and limited clamping losses.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

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.

The link between the dynamics of decision formation and movement is unclear. Here the authors reveal a tight relationship between evidence accumulation during perceptual decisions and response trajectories observed in rats and humans.

Analysis of the spread of the 20E (EU1) variant of SARS-CoV-2 through Europe suggests that international travel and insufficient containment, rather than increased transmissibility, led to a resurgence of infections.

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.

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.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Magneto-ionics are a promising approach for controlling magnetism via electric fields, but most studies have been limited to thin films, rather than the nanostructures that would form the basis of a magneto-ionic memory unit. Here, Spasojevic et al demonstrate magneto-ionic control over transitions among paramagnetic, single domain, and vortex states in an array of nanodots.

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.

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.

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.

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.

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.

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

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.

Bidirectional neural interface electronic devices offer therapeutic options. Here, the authors present wafer-scale fabrication of flexible nanoporous graphene-based implantable microelectrode arrays with low impedance and high charge injection for in vivo brain recording and nerve stimulation.

Here, the authors identify B lymphocyte antigen CD20 as a marker for HIV-infected T cells and provide evidence for the potential use of anti-CD20 antibodies in combination with latency reversing agents for depletion of viral reactivated CD4 T cells in patients on antiretroviral therapy.

In this era of rapidly expanding human genomics in research and healthcare, efficient data reuse is essential to maximize benefits for society. In response, the Federated European Genome–Phenome Archive (FEGA) was launched in 2022, and as of 2024, the FEGA network was composed of seven national nodes. Here we describe the complexities, challenges and achievements of FEGA, unravelling the dynamic interplay of regulatory frameworks, technical challenges and the shared vision of advancing genomic research.

Standard platinum-based chemotherapy is the basis of treatment of many cancers, however a proportion of patients do not derive benefit. Here the authors show that the platinum-based drug oxaliplatin accumulates in cancer-associated fibroblasts, activating pathways associated with cancer progression and resistance to therapy.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Lung resident memory T (T_RM) cells are important for protection from viral infection in the lungs. Here the authors use paired lung biopsy material and blood to characterize T cell responses in patients with COVID-19 over time and find persistence of antiviral lung T_RM cells that might be important to limit reinfection.

α-Synuclein (αS) aggregation is a driver of several neurodegenerative disorders. Here, the authors identify a class of peptides that bind toxic αS oligomers and amyloid fibrils but not monomeric functional protein, and prevent further αS aggregation and associated cell damage.

The generation of patient-specific induced pluripotent stem cells (iPS cells) is thought to hold great therapeutic potential. Here, somatic cells from Fanconi anaemia patients are reprogrammed to pluripotency after correction of the genetic defect, generating patient-specific iPS cells.

In an early-phase lentiviral gene therapy trial, gene-corrected autologous hematopoietic stem cells show sustained engraftment and phenotypic correction in non-conditioned patients with Fanconi anemia.

Genome sequences of human-infective tapeworm species reveal extreme losses of genes and pathways that are ubiquitous in other animals, species-specific expansions of non-canonical heat shock proteins and families of known antigens, specialized detoxification pathways, and metabolism that relies on host nutrients; this information is used to identify new potential drug targets.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.