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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.

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.

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.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Microscopic colitis is a chronic inflammatory disease of the large intestine. Here the authors use single-cell RNA transcriptomic profiling and tissue localization studies to characterise the colon immune cell populations in MC, showing expansion of CD8 T cells with diverse TCR clonotypes and expression of CD4 T reg cell signatures.

Aspartoacylase expression in white adipose tissue regulates circulating levels of N-acetylaspartate, which in turn modulates plasma pyrimidine levels and regulates postprandial body temperature.

Regioselectivity during electrophilic aromatic substitution is typically controlled by substituents on the aryl group. Here the authors report an electrophilic aromatic substitution reaction, wherein remote chiral ester groups direct the electrophile to a precise location on the molecule.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Group II introns are large, self-splicing RNAs that catalyze their own excision from pre-mRNA molecules. Here the authors determine the 3.7 Å crystal structure of the group II intron in the stage immediately before the second step of splicing and present a complete model for the second step of group II intron splicing.

A data-efficient deep learning model developed to predict ground-state and photophysical properties of molecules and nanomaterials by learning many-body Green’s functions achieves an accuracy surpassing the state-of-the-art density functional theory calculations.

A pulse of ocean acidification is reconstructed from the boron isotope composition of fossilized oysters at the Triassic-Jurassic boundary, implicating ocean acidification from volcanic outgassing as a kill mechanism during the extinction event.

The Verwey transition in magnetite was reported 80 years ago but identifying the underlying mechanism has been difficult. Here the authors show that structural distortions associated with the Verwey transition emerge as local fluctuations at the Curie temperature, confirming their link with magnetic order.

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.

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.

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.

The cell adhesion molecule E-selectin regulates haematopoietic stem cell self-renewal in the bone marrow vascular niche. Here, the authors show E-selectin adhesion directly induces survival signaling in acute myeloid leukaemia and therapeutic inhibition improves chemotherapy outcomes in mice.

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.

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.

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.

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.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

A clinical study of women with abnormal breast mammograms establishes a workflow to evaluate the capability of breast photoacoustic computed tomography in the classification, monitoring and segmentation of lesions.

Uechi et al. found that a small-molecule lipoamide dissolves stress granules (SGs) by targeting SFPQ, a redox-sensitive disordered SG protein, alleviating pathological phenotypes caused by amyotrophic lateral sclerosis-associated FUS and TDP-43 mutants.

Tröger et al. identify a positioning and tethering process ensuring proper mitochondrial distribution during dendritic arbor formation of neurons and reveal the first molecular players - rhotekin2 and syndapin I - and underlying mechanisms.

The morphogenetic events that occur during gastrulation involve dramatic cell- and tissue-level changes. Here they show that propagation of nematic order, leading to long-range spatial correlation, is universally conserved during metazoan embryogenesis.

Repeated vaccination is needed to maintain high levels of SARS-CoV-2 immunity in vulnerable populations, but there is concern that it could lead to immune exhaustion. Here, the authors assess the evidence for immune exhaustion following multiple SARS-CoV-2 vaccination three vulnerable population cohorts in Canada.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

A soft mesh microelectrode array can seamlessly integrate in developing brains, enabling long-term, stable mapping of how single-neuron activity and population dynamics emerge and evolve during brain development.

Progranulin deficiency causes untreatable neurodegenerative diseases. Here, the authors show that hematopoietic stem cell transplantation and optimized brain conditioning correct the disease phenotype in progranulin-deficient mice.

A predictive model has been created for a stereoselective palladium-catalysed allylic amination reaction. Derived only from quantum chemical data, the method is accurate enough to reveal multiple erroneous assignments in literature experiments.

Antibody and antibody-avidity assays relying on near-infrared-fluorescence amplification by nanostructured plasmonic gold substrates accurately quantify antibodies to SARS-CoV-2 and to common viruses in human serum and saliva.

A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve outcomes.

Dissecting the causal relationship between genotype and phenotype can be challenging, Here, the authors develop Worm Perturb-Seq, a high throughput sequencing and analytical framework to assess transcriptomic changes upon gene perturbation in whole C. elegans.

Co-occurring mutations in the tumor suppressor LKB1 are frequent in KRAS-mutant lung cancers. Here, the authors show that LKB1 regulates JNK-dependent stress signaling apoptotic dependencies of KRAS-mutant tumors, making LKB1-deficient cells vulnerable to MCL-1 inhibition.

Detecting dilute airborne biomarkers is important in healthcare but is limited by the low sensitivity of current gas sensors. A portable, low-cost device is introduced that uses water condensation to enrich airborne biomarkers into a concentrated liquid, enabling existing liquid sensors to detect biomarkers with high sensitivity and broad accessibility.