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Новое в науке на 2023-02-05

ShrinkCRISPR: a flexible method for differential fitness analysis of CRISPR-Cas9 screen data

CRISPR screens provide large-scale assessment of cellular gene functions. Pooled libraries typically consist of several single guide RNAs (sgRNAs) per gene, for a large number of genes, which are transduced...

2023-02-03

Mutational signatures in human small intestinal crypts indicate APOBEC mutagenesis

Using laser-capture microdissection and whole-genome sequencing of individual crypts, we characterized the landscape of somatic mutations in human small intestinal epithelium. Mutational signatures of APOBEC mutagenesis were found frequently and are probably due to the activity of APOBEC1, which is expressed at high levels in the small intestine.

2023-02-02

Sox2 expression can be regulated across boundaries generated by CTCF–cohesin loops

Using a series of mouse mutants, we found that the Sox2 promoter does not require CTCF–cohesin loops to interact with distal enhancers. Surprisingly, mice with varying numbers of CTCF motifs in different positions showed that some distal enhancers can bypass boundaries that are created by CTCF–cohesin loops to ensure robust Sox2 expression.

2023-02-02

Master kinases extracted from proteogenomic networks in glioblastoma drive cancer subtypes

Using an unbiased algorithm based on kinase–phosphorylation site interactions that is applicable to any proteomic dataset, we identified and experimentally validated two protein kinases (PKCδ and DNA-PKcs) as the master kinases that drive two functional subtypes of glioblastoma multiforme and are potential therapeutic targets of other cancer subtypes.

2023-02-02

The repertoire of mutational signatures in childhood cancer

Somatic mutations in cancer genomes are caused by multiple mutational processes, each generating characteristic mutational signatures. Our systematic mutational signature analysis of single base substitutions and small insertions and deletions in pediatric cancers indicates that the contribution of signatures of homologous recombination repair defect is limited and identifies a leukemia-specific signature.

2023-02-02

A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling

Fendt and colleagues find that pre-metastatic niche formation and a high-fat diet increase palmitate availability in future organs of metastases and show that breast cancer cells use palmitate to generate acetyl-CoA, acetylate the NF-κB subunit p65 and induce pro-metastatic signaling.

2023-02-02

Integrative multi-omics networks identify PKCδ and DNA-PK as master kinases of glioblastoma subtypes and guide targeted cancer therapy

Iavarone and colleagues develop a computational approach called SPINKS to identify master kinases for functional subtypes of human glioblastoma defined using integrated multi-omics data, which show potential as subtype-specific therapeutic targets.

2023-02-02

GACNNMDA: a computational model for predicting potential human microbe-drug associations based on graph attention network and CNN-based classifier

As new drug targets, human microbes are proven to be closely related to human health. Effective computational methods for inferring potential microbe-drug associations can provide a useful complement to...

2023-02-02

When transcription initiation meets chromatin

Gene transcription initiation is a highly regulated process in which Pol II and general transcription factors assemble into a pre-initiation complex. Structural studies of yeast and human initiation complexes shed light on the role of the first nucleosome flanking gene promoters in controlling the transcription machinery.

2023-02-01

CRISPR–Cas has a new juggling act: interplay between nuclease and protease

Craspase is newly identified type III CRISPR–Cas system with two major components: the nuclease Cas7-11, and the protease TPR-CHAT. Craspases perform a delicate balancing act between nuclease and protease activity to achieve immune tolerance and defense in bacteria, and show promise as highly regulatable genome-editing tools.

2023-01-31

Who signs the paper?

Authorship on a paper gives credit where it is due, but it also comes with responsibilities. Here we discuss our policies and offer advice on best practice.

2023-01-31

Two approaches to tackling COVID-19 in patients with blood cancer

Patients with blood cancer have fewer antibodies after SARS-CoV-2 vaccination — but recent work shows that these antibodies seem to bind to viral spike protein more strongly than those in matched controls. In addition, another study finds that convalescent or vaccinee plasma might improve COVID-19 outcomes in those with blood cancer.

2023-01-31

Inflammation meets translation in AML

Acute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and treatment options. A new study reveals a unique inflammatory signature in pediatric and adult AML malignant cells that is associated with the infiltration of atypical B cells in the bone marrow microenvironment, which adds an independent layer of prognostic information.

2023-01-31

PP-DDP: a privacy-preserving outsourcing framework for solving the double digest problem

As one of the fundamental problems in bioinformatics, the double digest problem (DDP) focuses on reordering genetic fragments in a proper sequence. Although many algorithms for dealing with the DDP problem...

2023-01-31

Systematic and benchmarking studies of pipelines for mammal WGBS data in the novel NGS platform

Whole genome bisulfite sequencing (WGBS), possesses the aptitude to dissect methylation status at the nucleotide-level resolution of 5-methylcytosine (5-mC) on a genome-wide scale. It is a powerful technique...

2023-01-31

Enhancer–promoter interactions can bypass CTCF-mediated boundaries and contribute to phenotypic robustness

Genetic manipulation of the Sox2 locus in mice shows that gene activation by distal enhancers does not require CTCF-mediated loops and can occur across ectopic CTCF-mediated boundaries. The ability to bypass CTCF boundaries varies with their insulation strength and the tissue-specific enhancers responsible for activation.

2023-01-30

GENTLE: a novel bioinformatics tool for generating features and building classifiers from T cell repertoire cancer data

In the global effort to discover biomarkers for cancer prognosis, prediction tools have become essential resources. TCR (T cell receptor) repertoires contain important features that differentiate healthy...

2023-01-30

APOBEC mutagenesis is a common process in normal human small intestine

Whole-genome sequencing of healthy human epithelial crypts from the small intestines of 39 individuals highlights APOBEC enzymes as a common contributor to the overall mutational burden in this tissue.

2023-01-26

Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing

A multi-ancestry transcriptome-wide association study using an optimal linear combination of association statistics provides insights into tobacco use biology and suggests opportunities for drug repurposing.

2023-01-26

Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains

Genome-wide analyses identify 27 loci associated with attention-deficit hyperactivity disorder and provide insights into its genetic architecture in relation to other psychiatric disorders and cognitive traits.

2023-01-26

EGOC inhibits TOROID polymerization by structurally activating TORC1

Determination of the high-resolution structure of yeast TORC1 allows characterization of the precise interfaces of interaction between inactive TORC1 and TORC1′ polymers and identification of the mode of binding of active EGOC on TORC1.

2023-01-26

Comprehensive analysis of mutational signatures reveals distinct patterns and molecular processes across 27 pediatric cancers

Jäger and colleagues analyze single-base substitution and indel mutational signatures across 27 pediatric cancer types, revealing marked differences in mutational patterns compared with adult cancers and insights into underlying molecular mechanisms.

2023-01-26

Towards a structurally resolved human protein interaction network

Here the authors explore the ability of AlphaFold2 to predict structures across the human protein-protein interactome and the limitations thereof.

2023-01-23