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Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Here, the authors apply a standardized system, called TXsystem, to transplant wild mouse gut microbiota into SPF mice, developing “TXwildlings” mice that stably retain natural microbiota and human-like immune traits, enhancing reproducibility and translational relevance.

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.

Artificial intelligence (AI) system is known to improve dermatologists’ diagnostic accuracy for melanoma. This group applies the eye-tracking technology on dermatologists when diagnosing dermoscopic images of melanomas and reports improved balanced diagnostic accuracy when using an X(explainable) AI system comparing to the standard one.

Experiments show that olivine is transparent at high pressure and temperature, with radiative heat transport representing 40% of olivine’s thermal conductivity. Heat radiation enhances slab’s heating rate and affects subduction dynamics.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

This flagship study from the European Solve-Rare Diseases Consortium presents a diagnostic framework including bioinformatic analysis of clinical, pedigree and genomic data coupled with expert panel review, leading to 500 new diagnoses in a cohort of 6,000 families with suspected rare diseases.

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.

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.

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.

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.

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

Using sequencing and haplotype-resolved assembly of 65 diverse human genomes, complex regions including the major histocompatibility complex and centromeres are analysed.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

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.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

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.

Photoionization of atoms and molecules is a complex process and requires sensitive probes to explore the ultrafast dynamics. Here the authors combine transient absorption and photo-ion spectroscopy methods to explore and control the attosecond pulse initiated excitation, ionization and Auger decay in Kr atoms.

Massive subduction and continental crust production during the Earth’s first 500 million years is suggested by the composition of a 4.3 Ga old mantle source of melt included in olivine from Archean komatiites and geodynamic models.

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.

Inter-particle reactions in weakly bound systems are often difficult to pinpoint by detecting exclusively the kinetic energy of the produced ions. Here the authors present a full-coincidence experiment, where inter-particle reaction channels are determined by the measurement of all outgoing particles.

Genomic analysis of Plasmodium DNA from 36 ancient individuals provides insight into the global distribution and spread of malaria-causing species during around 5,500 years of human history.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Here, Libertini and colleagues devise a computation tool that can analyze whole-genome bisulfite sequencing (WGBS) data to recover of ∼30% of the lost differential methylation position information. They use COMETgazer and COMETvintage to analyze 13 diffferent methylome data to demonstrate their performance.

Rudalska et al. describe a novel class of p38α inhibitors with increased target residence time. They explore the drugs’ specificity, pharmacokinetics and toxicity profile and show that they are efficacious in the context of colorectal cancer.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Machine learning models represent an opportunity for the automatic generation of histopathology reports. Here, the authors develop HistoGPT, a vision language model that can generate reports from multiple gigapixel-sized whole slide images and also predict tumour thickness, subtypes, and margins, among other diseases.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

Aldol condensation is an important reaction in polymer synthesis, but due to the lack of reliable analytical methods, direct evidence of the polymer microstructure and sequence has remained elusive. Here, the authors combine electrospray deposition and scanning tunnelling microscopy to image four n-type polymers at sub-monomer resolution, revealing and quantifying unexpected structural defects intrinsic to the aldol condensation process.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

Reducing the signal-to-noise ratio is a never-ending challenge for many types of experiments. Now, improved ratios are reported for nuclear magnetic resonance set-ups combining an external high-Q resonator and a low-Q input coil.

Most genomics research cohorts are made up of participants of European ancestry, which limits the reach of precision medicine. Here, the authors describe the genetic diversity in the All of Us research program, which is enriched in underrepresented ancestries.

Hepatitis B virus is an almost uniquely human-tropic pathogen for which model systems are scarce. Here, the authors determine key residues within the HBV receptor that form a barrier in the HBV life cycle in primates and identify marmosets as a model candidate for infection with simian-tropic HBV.

Keyl et al. present an explainable artificial intelligence model-based real-world data analysis from over 15,000 patients across 38 cancer types, identified key prognostic marker interactions, and confirmed these in an external lung cancer cohort.

Venous tumour thrombus can occur within renal cell carcinoma, and can require complex additional surgery and treatment. Here, the authors analyse multiparametric data from patients treated with axitinib and develop a machine learning model to predict neoadjuvant treatment response.