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One-step, generalizable conversion of aromatic rings into heteroaromatic rings remains a challenge in organic chemistry. Here, the authors developed a heteroaromatic swapping reaction for aromatic ketones with broad substrate range and high selectivity.

A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

Mohri et al. show that, in response to genotoxic stress, melanocyte stem cells undergo senescence-associated differentiation, causing their depletion and protecting them against melanomagenesis. This process is suppressed by carcinogens.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

Lineage switching (LS) facilitates acute myeloid leukemia (AML) escaping CD19 targeted immunotherapy, but the underlying mechanism are not well understood. The authors here analyze patients’ single-cell mass cytometry and single-cell transcriptomics data, and identify an LS AML with the MDSC-like phenotype which is associated with LS in AML with KMT2A rearrangement.

Molecular biomarkers of recurrence in colorectal cancer (CRC) generally cannot capture spatial information about the tumour and its microenvironment. Here, the authors develop HIBRID, a deep learning model to predict disease-free survival in CRC from histopathology whole slide images, improving risk stratification in large cohorts.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

Clinical manifestations in patients with systemic sclerosis (SSc) are highly heterogeneous, and identifying the root causes of clinical symptoms is challenging. Here, by performing single-cell profiling of peripheral blood from SSc patients, the authors identify distinct immune abnormalities associated with acute organ complications, including interstitial lung disease and scleroderma renal crisis.

The herpes simplex virus 1 uracil-DNA glycosylase counters host APOBEC1 to evade genome editing and to enable viral replication that promotes encephalitis in mice.

In a large cohort with a 23-month median follow-up of the CIRCULATE-Japan GALAXY observational study, ctDNA-based detection of molecular residual disease was predictive of survival outcomes and benefit of adjuvant chemotherapy in patients with resectable colorectal cancer.

Residual stress in crystalline polymers can lead to material failure, but currently methods which can quantify residual stress in such materials are lacking. Here, by using fluorescent-type mechanochromophores, the authors develop a method to visualize and quantify low degrees of stress that arises from micro-mechanical forces during polymer crystallization.

Ecto-nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein that hydrolyzes both ATP and cGAMP. Here the authors present the crystal structures of the extracellular domain of mouse ENPP1 in complex with 3′3′-cGAMP and the reaction intermediate pA(3′,5′)pG and discuss mechanistic implications.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

Bando et al. perform a phase II trial of atezolizumab monotherapy following platinum-based definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma and report a complete response rate of 42%.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Zhaonella formicivorans produces methanol, for a novel syntrophic interaction, without requiring methylated compounds as an input.

In the observational GALAXY arm of the CIRCULATE-Japan study, among 1,049 patients with stage II–IV colorectal cancer, those with presence of circulating tumor DNA (ctDNA) after tumor resection have a high recurrence risk and are likely to benefit from adjuvant chemotherapy.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

The molecular heterogeneity of KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) remains poorly characterised. Here, the authors perform multi-omics analysis for 84 ALL patients and suggest 5 distinct subgroups for risk stratification and personalised treatment.’

Previously undescribed hierarchical arrangements in haematopoietic stem cells and their niches that mediate both regenerative potential and immune privilege are identified.

Photoisomerization of molecules is used to control the structure of soft matter but the response of molecules during isomerization is difficult to elucidate. Here the authors describe ultrafast formation of higher-orientation of liquid-crystalline azobenzene molecules via linearly polarized UV light using time-resolved electron diffraction.

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.

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.

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.

This study reports Stomidazolone, a doubly-sulfonylated imidazolone that inhibits stomatal differentiation by binding to the ACT-Like domain of MUTE, disrupting its interaction with the bHLH partner SCREAM, which expands the chemical toolkit for manipulating bHLH-ACTL protein interactions, offering new avenues for controlling plant development.

A cross-ancestry genomic and transcriptomic cohort of gastric cancer highlights significantly mutated genes and mutational signatures, some of which are ancestry-specific.

Back pain and sciatica are often caused by intervertebral disc degeneration. Sakai and colleagues identify a subset of nucleus pulposus progenitor cells from the intervertebral disc and show that loss of these progenitor cells correlates with ageing and intervertebral disc degeneration.

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.

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.

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.