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The gut microbiota may contribute to depression, but the underlying mechanism is not well understood. Here the authors use a mouse model of stress induced depression to demonstrate that behavioural changes conferred by fecal transplant from stressed to naïve mice require the endocannabinoid system.

Co-abundance analysis of 938 healthy individuals uncovers how host factors shape gut microbiome interactions, highlighting a core set of 200 impacted genera and additional factor-specific interactions.

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.

Including data from 1,047 patients across 19 inflammatory diseases, a new atlas presents a comprehensive model of inflammation in circulating immune cells.

IL-33 induces tertiary lymphoid structures.

Authors utilise a murine model of infection to provide mechanistic insight into how antimicrobial therapy may be a predisposing risk factor for hospital-acquired pneumonia. They show that antibiotic-induced microbiota perturbations compromise inflammatory monocytes and thereby impair antibacterial defence.

Authors used nanopore-based ITS2 sequencing analysis to map the global distribution of human-infecting Trichuris spp. They reveal a wide presence of T. incognita, its zoonotic potential, and provide insights for better control of infections.

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.

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.

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.

Cancer genetics has benefited from the advent of next generation sequencing, yet a comparison of sequencing and analysis techniques is lacking. Here, the authors sequence a normal-tumour pair and perform data analysis at multiple institutes and highlight some of the pitfalls associated with the different methods.

Local microbiome composition influences treatment efficacy of chemotherapy in colon cancer via modulation of tolerogenic versus immunogenic ileal intestinal epithelial cell death, which in turn influences follicular helper T cell priming.

Working with cancer genomes from multiple projects can increase investigative power, but quality of sequences can vary. Here, the authors present a framework for comparing whole genome sequencing quality to help researchers guide downstream analyses and exclude poor quality samples.

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.

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.

Cancer evolutionary dynamics are quantitatively inferred using a method, EVOFLUx, applied to fluctuating DNA methylation.

Accurate analysis of mitochondrial DNA is important for mitochondrial disease clinical research and diagnostics. Here, authors present a method using Cas9 cleavage, nanopore sequencing and a custom pipeline to identify pathogenic variants, deletions and accurately quantify heteroplasmy to below 1%.

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

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 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.

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.

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.

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.

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.

Examination of archaeological pottery residues and modern genes suggest that environmental conditions, subsistence economics and pathogen exposure may explain selection for lactase persistence better than prehistoric consumption of milk.

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.

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.

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.

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.

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.

Analysis of the genomes of 50 species of Lemuriformes shows high levels of genomic diversity, likely due to allele sharing, as well as population declines and inbreeding patterns resulting from ecological factors and human impacts in Madagascar.

Dendritic cells (DC) are important for maintaining immune homeostasis in the gut, but how they promote intestinal inflammation upon bacterial infection is still unclear. Here the authors show that IgA immune complexes induce proinflammatory cytokine production by metabolic reprogramming of otherwise tolerogenic human CD103⁺ DCs.

Trabjerg et al. show that the activity of carnitine palmitoyl transferase 1 (CPT1) and lipid metabolism are associated with the disease progression of the SOD1 G93A mouse model mimicking a motor neuron disease Amyotrophic lateral sclerosis (ALS). This study suggests CPT1 as a potential therapeutic target in treating ALS.

RNA sequencing of 465 human lymphoblastoid cell lines across seven European laboratories shows the feasibility of transcriptome sequencing for population-wide and cross-biobank studies.

The development of a new genetic tool to selectively deplete or modify group 2 innate lymphoid cells (ILC2s) addresses the debate regarding the non-redundant functions of this immune cell type.

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

Oxylipin profiling in the sea anemone Exaiptasia diaphana with different symbionts identifies stereospecific lipid signals. Results suggest that oxylipin regulatory pathways shape cnidarian–dinoflagellate symbiosis, homeostasis, and resilience.

Whole-genome alignment of 239 primate species reveals noncoding regulatory elements that are under selective constraint in primates but not in other placental mammals, that are enriched for variants that affect human gene expression and complex traits in diseases.

In cancer, global DNA methylation loss and CpG island hypermethylation are commonly observed. Here, in breast cancer the authors find that hyper-variability of partially methylated domains is the prime source of DNA methylation variation and that these domains fuel CpG island hypermethylation.

Multi-layered epigenetic regulation in higher eukaryotes makes it challenging to disentangle the individual effects of modifications on chromatin structure and function. Here, the authors expressed mammalian DNA methyltransferases in yeast, which have no DNA methylation, to show that methylation has intrinsic effects on chromatin structure.

Renal cancer accounts for 2.4% of all adult cancers and its incidence is increasing worldwide. Here, the authors carry out genome and transcriptome sequencing of clear cell renal cell carcinomas (ccRCCs) and highlight genomic aberrations and biological pathways underlying ccRCC tumorigenesis.