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Therapeutic T cells engineered to recognize tumour antigens are frequently short-lived and acquire unfavourable phenotypes in tumours. Here authors show that a tandem approach using autologous T cells targeted against the tumour antigen NY-ESO-1, followed by transfer of hematopoietic stem cells with the same specificity in the clinical trial NCT03240861, provides a safe and promising therapeutic option.

High-content protein arrays were used to identify cysteine dioxygenase (CDO1) as a small-molecule glue target for the von Hippel–Lindau (VHL) E3 ubiquitin ligase and induces VHL-dependent proteasomal degradation of CDO1 in cells.

Here the authors combine a deep generative model with structure-based drug design and prospectively validate functionally active, nanomolar, A_2A adenosine receptor ligands and solve their crystal structures to close the Artificial Intelligence Structure-Based Drug Design loop.

This analysis provides a collection of sequencing datasets generated from long-read and short-read RNA sequencing, serving as a valuable resource for transcriptome profiling.

A study presents a strategy based on human pluripotent stem cells for treating neurodegenerative disorders of the gastrointestinal tract.

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.

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.

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

Nonninger et al. identify the TFEB–TGFβ signaling axis as a regulator of stem cell resilience that protects against a senescence-like state during the adult diapause in Caenorhabditis elegans, a mechanism conserved in vertebrate aging and mammalian cancer.

Barcoding microbial ribosomal RNA creates a recording of gene transfer events without requiring translation.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

Lai et al. present the machine learning model MAARS to predict arrhythmic sudden cardiac death from multimodal imaging and clinical data in patients with hypertrophic cardiomyopathy.

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.

Wu et al. demonstrate that REM transcription factors and GDE1 guide RNA polymerase IV to specific genomic loci, establishing a DNA sequence-dependent mechanism for siRNA biogenesis and DNA methylation patterning.

Variation in responses to bacterial and viral stimuli between Batwa rainforest hunter-gatherers and Bakiga agriculturalists from Uganda suggests population-level divergence under natural selection, with hunter-gatherers disproportionately showing signatures of positive selection.

Vaccination efficiency in HIV infection is hampered by the low immunogenicity of HIV-1 Env glycoprotein (Env). Here authors optimise the neutralising antibody response to Env by stabilizing the Env trimers in the context of expressing them in a Newcastle Disease Virus-like particle and providing conditions that mimics replicating virus infection.

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.

Oxidized mitochondrial DNA can be released into cytoplasm activating the Nlrp3 inflammasome resulting in its extracellular release. Here the authors show that only this oxidized form can induce autoantibody production by uptake into plasmacytoid dendritic cells, which then produce interleukin-21 to differentiate naive T cells into T_FH cells.

The authors used long-read sequencing to reveal novel isoforms and differential transcript use in a transgenic model of tau pathology. Similar patterns were found in the human cortex, supporting a role for alternative splicing in Alzheimer’s disease.

High-resolution multi-omic profiling indicates widespread gut dysbiosis in individuals with MASLD, also affecting the virome, and reveals microbial signatures that can classify MASLD and its subtypes.

Comparing to Gossypium hirsutum, G. barbadense cotton lines have superior fiber quality but lower fiber yield. Here, the authors construct pangenome using 12 newly assembled G. barbadense genomes and 17 publicly tetraploid cotton genomes and reveal yield- and fiber-related diversity and interspecific gene flow.

Cryo-electron microscopy and biochemical studies elucidate the read–write mechanisms of non-canonical PRC1-containing RYBP in histone H2A lysine 119 monoubiquitination and their roles in maintaining epigenetic inheritance.

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.

Single cell analysis of histologic variant bladder tumors detects a shared CA125+ tumor cell state associated with aggressive clinical features and reveals enriched expression of TM4SF1, a membrane protein that can be targeted with CAR T cells.

Leveraging long-read RNA-seq data and machine learning, Bambu facilitates accurate transcript discovery and quantification.

Moroidins are plant ribosomally-synthesized and posttranslationally-modified peptides with anticancer activity. Here, the authors generate a searchable database of publicly available plant RNAseq data and identify a moroidin analog with higher cytotoxic activity.

This Registered Report presents the results of the Long-read RNA-Seq Genome Annotation Assessment Project, which is a community effort for benchmarking long-read methods for transcriptome analyses, including transcript isoform detection, quantification and de novo transcript detection.

Here, the authors created a virtual reality task for monkeys and mice to explore if internal states like attention are similar across species. Their facial expressions during the task were similar, suggesting facial expressions reflect shared internal states.

How lung epithelial and endothelial cells develop into alveoli is a major knowledge gap, with implications for lung repair in preterm infants. Here, the authors establish a transcriptomic atlas of human neonatal lung disease, identifying semaphorins as pivotal mediators of organogenesis and injury.

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.

CREBBP mutations in B-cell acute lymphoblastic leukemia (B-ALL) are linked to poor prognosis and chemoresistance. Here, the authors show that genetic or pharmacological inactivation of CREBBP sensitizes B-ALL cells to the BCL2 inhibitor Venetoclax, inducing ferroptotic cell death and extending survival in B-ALL preclinical mouse models.

Here the authors show that PD-1 controls coinhibitory receptor expression by T_reg cells. The absence of PD-1 expression could induce CD30 expression, thereby enhancing T_reg function and tumor escape, suggesting that CD30 might be a therapeutic target in cases of anti-PD-1 resistance.

A study of retrotransposon activity repurposes a retroelement called R2Tocc to create a programmable system called STITCHR that enables diverse genome edits including efficient, scarless large payload insertions.

Here, the authors show that base editing of CD33 and gamma globin genes in HSPCs results in the long-term engraftment of dual edited cells along with HbF reactivation and GO resistance in mice and nonhuman primates.

Zhou, Novak and colleagues identify that the Caenorhabditis elegans hypodermis, a peripheral liver-like metabolic tissue, regulates memory via insulin/IGF-1 and Notch signaling, and show that activating this pathway rescues CREB-dependent memory in aged worms.

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.

Cross-polarized stimulated Brillouin scattering and its integration with quadratic nonlinearity is studied in lithium niobate, which enhanced photonic device performance in a reconfigurable stimulated Brillouin laser with 0.7-Hz narrow linewidth and 40-nm tunability, an efficient coherent mode converter, and Brillouin-quadratic laser and frequency comb operational in near-infrared and visible bands.

Using a spatial reasoning task in mice, the authors show that retrosplenial cortex encodes spatial hypotheses with well-behaved recurrent dynamics, which can combine these hypotheses with incoming information to resolve ambiguities.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

DNA methylation drives parental expression differences at imprinted genes. Here, the authors uncover hundreds of ubiquitous and tissue-specific differentially methylated regions, offering insights into parental regulation and disease inheritance.

Infection by Plasmodium falciparum can manifest as diverse symptoms and outcomes with different treatment requirements. Here the authors use metabolomics, proteomics and transcriptomics data from 79 children to identify potential omics signatures that correlate with different extent and nature of inflammation to provide insights into the development of future treatments.

Galsky and colleagues report the results of a phase 1 clinical trial of anti-programmed cell death protein 1 ligand 1 atezolizumab in combination with PGV001, a personalized neoantigen vaccine, in participants with urothelial cancer.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

Structural variants (SVs) in human genomes contribute diversity and diseases. Here, the authors use a multi-platform strategy to generate haplotype-resolved SVs for three human parent–child trios.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Mutations accumulate with age in the male germline, and can lead to genetic diseases in offspring. Here, the authors collect from individuals sequential sperm samples separated by long timespans, which they profile by high-fidelity sequencing to study germline mutation processes.

By bringing together whole exome and genome sequencing data from five cohorts, the authors assess the contribution of rare germline variants to prostate cancer risk and severity, further validating previously reported genes, and implicating a role for genes not previously reported.

Peer review information

Nature Communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.