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The fetal globin gene repressors BCL11A and ZBTB7A directly bind γ-globin gene promoter regions. Repressor binding is disrupted by naturally occurring point mutations located upstream of the transcriptional start site that are associated with hereditary persistence of fetal hemoglobin.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Cardiac fibrosis arises from persistent myofibroblast activity. This study reveals how chromatin factors control scar-forming cells in the heart and shows that inhibiting KAT5 can reduce harmful cardiac fibrosis.

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

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Two groups of ammonia-oxidizing archaea drive marine nitrification. Stuehrenberg et al. reveal that their distribution reflects substrate use, with one relying on urea and the other on ammonia to maintain nitrification in open-ocean waters.

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.

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.

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 RNAseq can struggle to capture cellular heterogeneity due to the relatively low expression of biologically meaningful transcripts. Here the authors present an approach called scCLEAN, which uses CRISPR/Cas9 to target and remove certain ubiquitous transcripts, thereby enhancing the detection of low-abundance transcripts.

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.

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.

Jin et al. discovered Atlantic grey seal milk contains 332 complex sugars, including 166 novel structures. Seal milk rivals human milk complexity, includes giant molecules up to 28 sugar units, changes during lactation, and shows immune-boosting effects.

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.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

Microbial communities are shaped by their environment. Here, the authors demonstrate temporal structuring of microbial communities in the pelagic Arctic Ocean, using remote, long-term sampling with long-read metagenomics and SSU ribosomal metabarcoding.

This study shows that expressing uncertainty about best- and worst-case effects of climate change on sea-level rise increases trust in climate scientists and message acceptance but not when the full extent of inevitable uncertainty due to unpredictable storm surges is also acknowledged.

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

High-coverage, ultra-long-read nanopore sequencing is used to create a new human genome assembly that improves on the coverage and accuracy of the current reference (GRCh38) and includes the gap-free, telomere-to-telomere sequence of the X chromosome.

Here the authors show that lab mice have retained ancient gut bacterial symbionts that diversified in parallel with rodent species, but the genomes of these gut bugs have accumulated mutational burdens over the past ~ 120 years of inbreeding in captivity.

Symbiont-housing structures are well-studied in multicellular eukaryotes but rarely in unicellular protists. This study shows that low-oxygen-adapted Anaeramoebae have symbiosomes positioning sulfate-reducing bacteria near hydrogenosomes, with genomic analyses suggesting likely metabolic interactions.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

The multikilobase reads that can be produced by single-molecule sequencing technologies may span complex, repetitive genomic regions but have high error rates. Bashir et al. use these reads to organize contigs assembled from accurate, short-read data, facilitating the analysis of clinically important regions of an outbreak strain of cholera.

Basal cell carcinoma is a common cancer among people of European ancestry, with associated high economic costs to monitor and treat. Here Stacey et al.conduct a genome-wide association study on Icelandic and other European populations, identifying four novel loci associated with cancer susceptibility.

CRISPR-TO, a system for programmable control of spatial localization of cellular RNAs, is presented and enables functional investigation of endogenous RNA localization in diverse living cells.

Germline pseudogenes have an important role in human evolution. Here, the authors analyse sequencing data from 660 cancer samples and find evidence for the formation of somatically acquired pseudogenes, a new class of mutation, which may contribute to cancer development.

Goel et al. examine why some factually correct news articles are often shared by users who also shared fake news articles on social media.

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.

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.

Wamaitha and colleagues used the rhesus macaque to characterize the transcriptional and spatial mechanisms underlying ovarian reserve formation in prenatal life providing insights into the molecular processes governing ovarian follicle establishment.

A phase I trial of a neoantigen-targeting personalized cancer vaccine led to durable and polyfunctional T cell responses and antitumour recognition, and was associated with no recurrence in patients with high-risk clear cell renal cell carcinoma.

While multiple resistance-to-Phytophthora sojae loci/alleles have been mapped in soybean, many of them have become ineffective to newly evolved isolates. Here, the authors show that a 27.7-kb nucleotide-binding site-leucine-rich repeat gene confers broad-spectrum resistance to P. sojae in soybean.

Retinoic acid is known to be effective against bone marrow metastatic neuroblastoma cells, but not primary tumors. Here, authors discover that bone morphogenetic protein signaling is responsible for determining neuroblastoma cell fate and sensitivity to retinoic acid.

Here, the authors investigate the relationship between HUSH-MORC2 and DNA methylation in embryo-derived human neural progenitor cells, enhancing the understanding of the epigenetic control of repeats in somatic cells.

Regev, Casto et al. examine the temporal response patterns of neural populations in the language network and discover that these populations process information over different timescales.

Genome complexity is a distinguishing feature of advanced cancers in contrast to precancerous conditions. Here, by analysing chromosomal copy-number evolution in early cancers and precancerous lesions of the oesophagus, the authors reveal signatures of ongoing chromosomal instability and its role in promoting tumour progression.

Circular extrachromosomal DNA in high-risk medulloblastoma contributes to tumor heterogeneity and associates with relapse and survival. Enhancer rewiring events involving known oncogenes are frequent events, affecting transcription and proliferation.

Mitochondria are essential cellular components that are found in animals, plants, fungi, and protists. This study reports what is believed to be the first example of complete mitochondrial loss in a free-living organism, providing insights into the evolutionary plasticity of eukaryotic cells.

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.

Ting and colleagues report the safety and efficacy of combined radiation and immunotherapy in a phase II trial on patients with MSS colorectal or pancreatic cancer and observe that disease control correlates with higher repetitive RNA transcription.

In this study, the authors report and analyze four complete genomes of respiratory endosymbionts to show that they carry the potential to breathe both oxygen and nitrogen oxides providing energy to their hosts. These organisms likely represent a snapshot in the evolutionary transition from symbiont to organelle.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Crossing the blood–brain barrier in primates is a major obstacle to gene delivery in the brain. Here an adeno-associated virus variant (AAV.CAP-Mac) is identified and demonstrated for crossing the blood–brain barrier and delivering gene sequences to the brain of different non-human primates species.

Analysis of genomic data from 981 colorectal cancers from participants in 11 countries reveals variations in mutational signatures of microsatellite-stable cancers that are dependent on geographical origin and age at which the cancer was diagnosed.