Search

In the Tumor Profiler proof-of-concept observational study, a multiomics approach for profiling tumors from patients with melanoma was feasible, returning data within 4 weeks and informing treatment recommendations in 75% of cases.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.

CRISPR enzymes require a defined protospacer adjacent motif (PAM) which can be limiting for editing applications. Here the authors recombine the PAM-interacting ___domain of SpRY with the N-terminus of Sc + + to generate a chimeric enzyme with highly flexible PAM preference: SpRYc.

The bioinformatics method COJAC enables improved population-level surveillance of the emergence and spread of SARS-CoV-2 variants in wastewater.

An analysis of fish and macroinvertebrate communities in European rivers over 32 years shows that inland ship traffic is associated with declining taxonomic richness, diversity and trait richness and with increased taxonomic evenness.

The helix–turn–helix ___domain of an anti-CRISPR-associated (Aca) protein represses transcription of anti-CRISPR (Acr)-encoding genes and inhibits their translation to protein via distinct binding modes to DNA and RNA, respectively.

TROVE2, a gene implicated in inflammatory response and autoimmunity, is also associated with enhanced memory for emotionally charged events in post-traumatic stress disorder.

Geographical hotspots with high frequency of multi-drug resistant tuberculosis (MDR-TB) have been observed in several locations, such as the country of Georgia. Here, the authors analyse genomic sequences from tuberculosis bacteria isolated from Georgia to show that the transmission fitness of MDR-TB strains is heterogeneous, and highly drug-resistant and transmissible isolates contribute to the emergence and maintenance of MDR-TB hotspots.

The basic five-digit limb of tetrapods has been altered many times during evolution, usually by the progressive loss of digits — this study tracks the molecular underpinnings of this change, showing that in comparison to mouse, the polarized gene expression in the bovine limb bud is progressively lost due to evolutionary alteration of the cis-regulatory sequences that control Ptch1 expression in response to SHH signalling in the digit-forming handplate.

The detection of subclonal variants in heterogeneous cancer specimens is a challenge due to errors that occur during sequencing. In this study, a statistical algorithm and a sequencing strategy are reported that circumvent this issue and can accurately detect variants at a frequency as low as 1/10,000.

Current methods to generate sequence-function data at large scale are either technically complex or limited to specific applications. Here the authors introduce DNA-based phenotypic recording to overcome these limitations and enable deep learning for accurate prediction of function from sequence.

Here, the authors structurally decipher how Cas12m2 protects against mobile genetic elements by tightly binding invading DNA via a unique arginine-rich cluster and its non-canonical RuvC site.

During spermatogenesis most histones are replaced with protamines. The distribution of the products of Trithorax and Polycomb histone modifications are now examined in both mouse and human sperm, showing conservation of histone methylation distribution across species. The authors propose a role for the Polycomb complex in transgenerational inheritance.

In this study, the authors provide a global overview of SARS-CoV-2 genome sequencing, and estimate the proportion of cases sequenced and time to genome upload. They identify disparities and highlight the need to strengthen surveillance in lower and middle income countries.

The authors show that circulating tumour cells can be found in association with neutrophils, an interaction which supports their proliferation and their ability to seed metastasis.

Therapeutic antibodies can be optimized using deep-learning models trained on antibody-mutagenesis libraries to generate antibody variants and predict their antigen specificity.

Liver-resident natural killer (NK) cells sustain the dormancy of disseminated breast cancer cells, and a decrease in NK cells and increase in activated hepatic stellate cells is associated with the formation of liver metastases.

Understanding the ecological drivers of highly transmissible, multidrug-resistant Mycobacterium tuberculosis.

How are specific genomic regions targeted for transcriptional silencing and how is stable silencing maintained? The Polycomb and heterochromatin silencing systems have distinct roles and yet share some interesting features, such as the involvement of non-coding RNAs, histone modifications and dynamic protein complexes.

CITE-seq analysis in healthy skin, and both primary vs. metastatic melanoma samples suggests practical considerations of different skin dissociation protocols and dynamic thresholding of antibody signals for biomarker discovery.

Accessibility may play a key regulatory role affecting factors that bind to or target DNA. Using accessibility to DNA methyltransferases, the genome-wide profile of DNA accessibility in Drosophila melanogaster is presented and analyzed, indicating correlations with PcG repression, H4K16 acetylation and replication initiation.

Dirk Schübeler, Michael Stadler and colleagues show that the c-Jun NH₂-terminal kinase (JNK) binds directly to active promoters during the differentiation of stem cells to neurons and targets histone H3 serine 10 for phosphorylation.

Fresh vs. slow-frozen tissues from various malignancies are compared for the establishment of 2D, 3D and ex vivo cultures, as well as for scRNAseq analysis, and found to be comparable and suitable for cancer research.

The authors present a robust diagnostic algorithm based on digital pathology and image analysis that quantifies intratumoral and stromal CD8+ T-cell densities in the tumor center and invasive margin compartment in metastatic melanoma. Spatial CD8+ T-cell densities are translated into the clinically relevant immune diagnostic categories “inflamed”, “excluded”, and “desert”. Their approach also allows efficient immune phenotyping of metastatic lesions, on biopsy material or even in the absence of material from the invasive margin.

CD98hc in macrophages attenuates the severity of colitis. This change in the macrophage development is associated with increased expression of apoptotic genes, suggesting that CD98hc maintains the gut homeostasis by ensuring the development of gut macrophages.