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Despite the progress in C(sp³) cross-coupling reactions, full control over the stereochemistry remains a challenge. Here, the authors show that phosphine-containing axially shielded Pd(II) complexes enable Suzuki-Miyaura cross-couplings of unactivated C(sp³) boronic acids with perfect stereoretention.

Polygenic scores and partitioned polygenic scores related to insulin resistance derived in multiancestry populations show distinct association with neurological outcomes

A low-cost robotic platform using mainly optical detection to quantify yields of products and by-products allows the analysis of multidimensional chemical reaction hyperspaces and networks much faster than is possible by human chemists.

Automated iterative small-molecule synthesis has generally been limited to around one carbon–carbon bond-forming step per day. Now, a next-generation automated synthesizer enables rapid, automated, iterative synthesis of a variety of small molecules. Improvements to chemistry and automation leads to a tenfold decrease in reaction time over previous automated platforms.

The ribosomal decoding center monitors accurate translation of 3-base mRNA codons. Here, the authors use cryo-EM to show how one of the monitoring bases of the ribosome enables a frameshift-inducing tRNA to instead read a 2-base codon.

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.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Identification of a hyperstable boronate enables automated lego-like synthesis to access a wider range of three-dimensionally complex small organic molecules rich in Csp³–C bonds. 

Elucidating specific effects of protein kinase Akt isoforms remains challenging. Here, the authors establish an Akt isoform-dependent cellular model system and use it, together with X-ray crystallography and structure-based ligand design, to develop isoform-selective covalent-allosteric Akt inhibitors

Enantioselective synthesis of atropisomeric biaryls is highly desirable due to the utility of these compounds as ligands and catalysts. Now, an organocatalytic polyketide cyclization is shown to convert poly-β-carbonyl compounds into binaphthalene derivatives in good enantioselectivities.

Parametric matrix models (PMMs) are a new class of machine learning methods using parametrized matrices to find implicit governing equations describing data. PMMs excel at making accurate predictions for scientific computing applications.

Mesocosm experiments revealed that both phytoplankton community composition and cellular acclimation influence marine particulate C:N:P ratios, with community shifts more sensitive to nitrogen supply and acclimation to the nutrient N:P supply ratio

Acoustic method could quickly catch counterfeit coins.

Organic chemical reactions can be divided into classes that allow chemists to use the knowledge they have about optimal conditions for specific reactions in the context of other reactions of similar type. Schwaller et al. present here an efficient method based on transformer neural networks that learns a chemical space in which reactions of a similar class are grouped together.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

The use and characterization of graphene quantum dots is limited by their pronounced tendency to form aggregates. Here, the authors synthesize rod-shaped motifs of nanographenes with up to 132 sp² carbon atoms that are fully individualized, which allows the precise description of their intrinsic photophysical properties.

An understanding of excess protons in nanoconfined water is highly relevant to technological applications such as fuel cell membranes. Here, ab initiosimulation reveals almost barrier-free proton transfer even in the limit of molecularly thin water films confined by mineral sheets.

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.

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.

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.

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.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Translating discovery scale vial-based batch reactions to continuous flow scale-up conditions is limited by significant time and resource constraints. Here, the authors report a photochemical droplet microfluidic platform, which enables high throughput reaction discovery in flow to generate pharmaceutically relevant compound libraries.

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.

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.

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.

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.

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 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 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.

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.

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.

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.

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.

Supersymmetric theories have partner bosonic and fermionic particles. Here, the authors use neutron spectroscopy on spin-ladder materials paired with matrix-product-states calculations to identify superpartner excitations.

Optimized SORT LNPs enable precise and long-lasting base editing in dual organs in a disease mouse model.

Mutations in RAS and PI3Kα drive cancer by activating the PI3K-AKT-mTOR pathway. The authors present RAS-PI3Kα structures, revealing interaction interfaces, isoform-specific differences, and a framework for designing PI3Kα-specific inhibitors.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.