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Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

CCR9 is chemokine receptor involved in gut inflammation and cancer. Here, the authors use AI-based modeling, protein engineering and pharmacological experiments to reveal the unusual anatomy of CCR9 activation by its endogenous chemokine agonist CCL25.

Colobomatous microphthalmia often lacks a genetic diagnosis despite its developmental complexity. Here, the authors show that rare variants in NR6A1 cause a syndromic form with eye, kidney, and vertebral defects, supported by zebrafish functional validation.

Magnetic skyrmions are promising objects for future spintronic devices. However, a better understanding of their dynamics is required. Here, the authors show that in contrast to predictions the skyrmion Hall angle is independent of their diameter and motion is dominated by disorder and skyrmion-skyrmion interactions in the system.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

Dengue (DENV) and Zika (ZIKV) viruses normally display as smooth spherical particles, while DENV can also become bumpy-surfaced, resulting in immune evasion. Here, Morrone et al. report DENV and ZIKV infectious club-shaped particles (clubSP) that display distinct antibody binding properties.

DeepRETStroke is a deep learning system using retinal photographs to detect silent brain infarction and predict future stroke events.

Fluorinated poly(aryl thioethers), unlike their poly(aryl ethers) counterparts, have received little attention despite excellent physical properties displayed by many polysulfides. Here the authors show a highly efficient route to fluorinated poly(aryl thioethers) via an organocatalyzed nucleophilic aromatic substitution of silyl-protected dithiols.

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.

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.

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 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.

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.

The genomic and immune landscape of pre-invasive lung adenocarcinoma is poorly understood. Here, the authors perform exome and transcriptome sequencing on precursor legions and invasive lung adenocarcinomas, identifying recurrently mutated genes in pre/minimally invasive cases, and arm level alteration events linked to immune infiltration.

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.

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.

A state-of-the-art generative artificial intelligence model of a video game is introduced to allow the support of human creative ideation, with the analysis of user study data highlighting three necessary capabilities, namely, consistency, diversity and persistency.

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.

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.

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.

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.

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.

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.

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.

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 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.

Tailored to provide diabetes management recommendations from large training and validation datasets, an artificial intelligence system integrating language and computer vision capabilities is shown to improve self-management of patients in a prospective implementation study.

A deep learning algorithm shows promising performance in predicting progression to diabetic retinopathy in patients, up to 5 years in advance, potentially providing support for medical treatment decisions and indications for personalized screening frequency in a real-world cohort.

Monolayer graphene in the quantum Hall regime exhibits a third-order nonlinear Hall response, which is robust against variations in magnetic field and temperature and provides insights into the interaction of chiral edge states.

Shen et al. report a method for multiplexing isogenic iPSCs for single-cell RNA-seq. With it, they created an atlas of in vitro differentiation and identified TMEM88 as a regulator of cardiovascular development, impacting blood pressure in adult mice.

Researchers developed an accurate model to analyse bivalent antibody binding. By analysing many SARS-CoV-2-specific antibodies, they found that their molecular reach can predict their neutralisation potency.

The extracellular secreted NS1 (sNS1) is a major factor contributing to dengue hemorrhagic fever. Here, Shu et al. report sNS1 exists in multiple oligomeric states and presents a tetrameric structure.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Ruminococcus gnavus is a mucus-associated gut commensal that can release the sialic acid, 2,7-anhydro-Neu5Ac. Here, the authors identify the pathway for its transportation and metabolism in R. gnavus, and show that this pathway is essential for its spatial localization in vivo.

Graphene has a centrosymmetric crystal symmetry, which prohibits second-order effects in transport experiments. Yet, giant second-order nonlinear transports can emerge in graphene moiré superlattices at zero magnetic field, originating from the skew scattering of chiral Bloch electrons in the superlattice and giving rise to both longitudinal and transverse nonlinear conductivities under time-reversal symmetry.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

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.

Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) regulate immune cell activities, including anti-tumor immune responses. Structures and visualization of human and mouse GITR–GITRL complexes offer insight into the architecture of higher-order membrane assemblies, and their signaling.

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.