Nanopore sequencing is an increasingly central tool for genomics. Despite rapid advances in the field, large data volumes and computational bottlenecks continue to pose major challenges. Here we introduce ex-zd, a new data compression strategy that helps address the large size of raw signal data generated during nanopore experiments. Ex-zd encompasses both a lossless compression method, which modestly

While the cohesin complex is a key player in genome architecture, how it localizes to specific chromatin sites is not understood. Recently, we and others have proposed that direct interactions with transcription factors lead to the localization of the cohesin-loader complex (NIPBL/MAU2) within enhancers. Here, we identify two clusters of LxxLL motifs within the NIPBL sequence that regulate NIPBL dynamics

Transposable elements (TEs) pose threats to genome stability. Therefore, small RNA-mediated heterochromatinization suppresses the transcription and hence the mobility of TEs. Paradoxically, transcription of noncoding RNA (ncRNA) from TEs is needed for the production of TE-targeting small RNAs and/or recruiting the silencing machinery to TEs. Hence, specialized RNA polymerase II (Pol II) regulators

Aptamers are short DNA or RNA sequences that can fold into unique three-dimensional structures, enabling them to bind specifically to target molecules with high affinity, similar to antibodies. A distinctive feature of many aptamers is their ability to adopt a G-quadruplex (G4) fold, a four-stranded structure formed by guanine-rich sequences. While G4 formation has been proposed or demonstrated for

Mutations in RecQ family helicases underlie human genetic disorders associated with genomic instability and cancer predisposition, but questions remain about how properly functioning RecQ reduces these deleterious effects. Importantly, some of the deleterious effects may result from incorrect repair of DNA double-strand breaks (DSBs) by recombinase proteins. Displacement loops (D-loops) are three-strand

CRISPR-dependent base editing (BE) enables the modeling and correction of genetic mutations at single-base resolution. Base editing screens, where point mutations are queried en masse, are powerful tools to systematically draw genotype–phenotype associations and characterise the function of genes and other genomic elements. However, the lack of user-friendly web-based tools for designing base editing

One of the major challenges in precision oncology is the identification of pathogenic, actionable variants and the selection of personalized treatments. We present Onkopus, a variant interpretation framework based on a modular architecture, for interpreting and prioritizing genetic alterations in cancer patients. A multitude of tools and databases are integrated into Onkopus to provide a comprehensive

Antisense oligonucleotides (ASOs) are a promising class of gene therapies that can modulate the gene expression. However, designing ASOs manually is resource-intensive and time-consuming. To address this, we introduce a user-friendly web server for ASOptimizer, a deep learning-based computational framework for optimizing ASO sequences and chemical modifications. Given a user-provided ASO sequence,

LitSense 2.0 (https://www.ncbi.nlm.nih.gov/research/litsense2/) is an advanced biomedical search system enhanced with dense vector semantic retrieval, designed for accessing literature on sentence and paragraph levels. It provides unified access to 38 million PubMed abstracts and 6.6 million full-length articles in the PubMed Central (PMC) Open Access subset, encompassing 1.4 billion sentences and

LIGYSIS-web is a free website accessible to all users without any login requirement for the analysis of protein-ligand binding sites. LIGYSIS-web hosts a database of 65,000 protein-ligand binding sites across 25,000 proteins. LIGYSIS sites are defined by aggregating unique relevant protein–ligand interfaces across different biological assemblies of the same protein deposited on the PDBe. Additionally

Adeno-associated virus (AAV) capsid engineering is essential for advancing gene therapy but remains limited by structural complexity and computational constraints. To address these challenges, we developed CapBuild, a cloud-native web server that streamlines AAV capsid prediction, assembly and engineering. CapBuild provides two distinct workflows: a PDB-based pipeline for assembling complete capsids

We present the CellHit web server (https://cellhit.bioinfolab.sns.it/), a web-based platform designed to predict and analyze cancer patients’ responsiveness to drugs using transcriptomic data. By leveraging extensive pharmacogenomics datasets from the Genomics of Drug Sensitivity in Cancer v1 and v2 (GDSC) and Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) and transcriptomic data

Protein–protein interactions (PPIs) are central to many cellular processes, and the assembly of proteins into complexes is essential for biological function. Clustering with overlapping neighborhood expansion (ClusterONE) has been successfully used to detect overlapping protein complexes in both weighted and unweighted PPI networks. Here, we present ClusterONE Web, a freely available, web-based tool

Huntington’s disease belongs to a class of repeat expansion disorders whose pathology is marked by the expression of toxic polyglutamine-containing proteins that assemble into insoluble protein aggregates. To study factors that influence the solubility of native polyglutamine-containing proteins, Saad et al. focused on FOXP2, a transcription factor harboring a stretch of 40 consecutive glutamines.

The mechanisms underlying the extreme folding and contraction of genomic DNA into mitotic chromosomes remain incompletely understood. To address this, Jan Ellenberg and colleagues applied a DNA-tracing approach previously established for interphase cells that is based on fitting of sequentially resolved DNA fluorescence in situ hybridization (FISH) signals, using a FISH probe library they designed

In eukaryotes, transcription factors (TFs) are known to regulate transcription by binding to the enhancers and promoters of target genes. Despite extensive research on this topic, numerous questions about TF specificity, cooperativity and function remain unanswered. To address some of these in a systematic way, Mahendrawada et al. used yeast as a model organism, owing to its relatively small number

Living ape species are close evolutionary relatives of humans and their genomes are essential for human genomic and evolutionary studies. Yoo et al. generated complete genome assemblies of six ape species: chimpanzee (Pan troglodytes), bonobo (Pan paniscus), gorilla (Gorilla gorilla), Bornean orangutan (Pongo pygmaeus), Sumatran orangutan (Pongo abelii) and siamang (Symphalangus syndactylus). For diploid

Switchgrass (Panicum virgatum L.) is a bioenergy and forage crop. Upland switchgrass exhibits superior cold tolerance compared to the lowland ecotype, but the underlying molecular mechanisms remain unclear. Here, we present a high-quality haplotype-resolved genome of the upland ecotype “Jingji31.” We then conduct multi-omics analysis to explore the mechanism underlying its cold tolerance. By comparative

The relationship between TP53 and transposable elements (TEs) has been obscure. Given the important role of TEs in oncogenesis, a comprehensive profiling of TE expression dynamics under the regulation of TP53 provides valuable resources for more clarity in TP53's roles in cancer. In this study, we characterized the TE transcriptomic landscape using long-read RNA-seq and short-read RNA-seq in three

Recent developments in spatial omics are revoluzionating our understanding of tissue structures organization and their deregulation in disease. Here, we present a strategy for capturing chromatin histone modification signatures across tissue sections by taking advantage of a double-barcoded DNA arrays design compatible with in situ protein A-Transposase Tn5 tagmentation. This approach has been validated

The integrated stress response (ISR) is critical for resilience to stress and is implicated in numerous diseases. During the ISR, translation is repressed, stress-induced genes are expressed, and mRNAs condense into stress granules. The relationship between stress granules and stress-induced gene expression is unclear. We measured endogenous stress-induced gene mRNA localization at the single-molecule

Nonsense-mediated RNA decay (NMD) is a highly conserved RNA turnover pathway that influences several biological processes. Specific features in messenger RNAs (mRNAs) have been found to trigger decay by NMD, leading to the assumption that NMD sensitivity is an intrinsic quality of a given transcript. Here, we provide evidence that, instead, an overriding factor dictating NMD sensitivity is the cell

Horizontal gene transfer plays a critical role in microbial genome evolution and adaptation. Integrated foreign DNA fragments encompass various types of mobile genetic elements (MGEs), ranging from small transposons to conspicuous integrative and conjugative elements. These regions often confer advantageous traits, including antibiotic resistance or novel metabolic capabilities, and contain foreign

Large-scale analyses of bacterial genomic datasets contribute to the comprehensive characterization of complex microbial dynamics among different strains and species. Such analyses often include open reading frame extraction, orthogroup inference, phylogeny reconstruction, and functional annotation of proteins. We have previously developed the M1CR0B1AL1Z3R web server, a “one-stop shop” for conducting

Atomic structure modeling is a crucial step in determining the structures of protein complexes using cryo-electron microscopy (cryo-EM). This work introduces DEMO-EMol, an improved server that integrates deep learning-based map segmentation and chain fitting to accurately assemble protein–nucleic acid (NA) complex structures from cryo-EM density maps. Starting from a density map and independently modeled

Understanding cell–cell communication (CCC) pathways from single-cell or spatial transcriptomic data is key to unraveling biological processes. Recently, multiple CCC methods have been developed but primarily focus on refining ligand–receptor (L-R) interaction scores. A critical gap for a more comprehensive picture of cellular crosstalks lies in the integration of upstream and downstream intracellular

Simulating protein structure flexibility using classical methods is computationally demanding, especially for large proteins. To address this challenge, we have been developing the CABS-flex method, which enables fast simulations of protein structural flexibility by combining a coarse-grained simulation approach with all-atom detail. Previously available as the CABS-flex 2.0 web server, the method

Our web server MAGNETIC (Motif Associated Gene NETworks in Chromosomes) allows users to search the human genome for correlations between promoter regions of genes. The correlations take into consideration the similarity of the abundance of 5/6-mer motifs in gene promoters. The promoters could be 1, 2, or 6 kb upstream of the gene start site. Genes with similar motif abundances are linked to form a

The rapid advance of spatially resolved transcriptomics technologies has yielded substantial spatial transcriptomics data. Deriving biological insights from these data poses nontrivial computational and analysis challenges, of which the most fundamental step is spatial domain detection (or spatial clustering). Although a number of tools for spatial domain detection have been proposed in recent years

Accurate and accessible phylogenetic analysis is essential for understanding microbial taxonomy and evolution, which are integral to microbiology, ecology, and drug discovery, yet it remains a challenging task. AutoMLST2 (https://automlst2.ziemertlab.com) is a web server designed to facilitate automated phylogenetic reconstruction and microbial taxonomy analysis for bacterial and archaeal genomes.

Drosophila melanogaster has one of the deepest research bases within the life sciences, with a wealth of high-quality tissue- and cell type-specific transcriptomic data available. However, integrating large datasets derived from disparate sources is not trivial. We have designed a broadly applicable solution to this problem in the form of the Drosophila Interesting Genes in Individual Tissues-tally

BioPortal (https://bioportal.bioontology.org) is the world’s most comprehensive repository of biomedical ontologies. It provides infrastructure for finding, sharing, searching, and utilizing biomedical ontologies. Launched in 2005, BioPortal now includes 1549 ontologies (1182 of them public). Its open, freely accessible website enables anyone (i) to browse the ontology library, (ii) to search for terms

CTCF, a highly studied transcription factor, is essential for chromatin interaction maintenance. Several independent studies report that CTCF interacts with RNAs in vitro and in cells. Yet continuous debates about the authenticity of the RNA-binding affinity of CTCF and its biological role remain in large part due to limited research techniques available, such as CLIP-seq. Here, we investigate RNA’s

In this Journal Club, Tracy Bedrosian describes a 2001 paper by Rehen et al. that provided early evidence of pervasive somatic variation throughout the human brain.

Premature stop codon–containing mRNAs can produce truncated and dominantly acting proteins that harm cells. Eukaryotic cells protect themselves by degrading such mRNAs via the nonsense-mediated mRNA decay (NMD) pathway. The precise reactions by which cells attack NMD-target mRNAs remain obscure, precluding a biochemical understanding of NMD and hampering therapeutic efforts to control NMD. Here, we

To investigate the pathogenesis and target the vulnerability of human pineoblastoma, researchers have developed multiple genetically engineered mouse models that represent distinct molecular subtypes of the disease. In this issue of Genes & Development, Fraire and colleagues (doi:10.1101/gad.352485.124) examined the roles of key microRNA (miRNA) processing components Drosha and Dicer1. Loss of either

Cohesin contributes to genome spatial organization and sister chromatid cohesion. In this way, it not only supports accurate chromosome segregation and efficient DNA repair but also regulates gene expression. These functions are essential during embryonic development, the process that converts the fertilized egg into a complex organism with billions of specialized cells organized into tissues and organs

All cellular functions rely on accurate protein biosynthesis. Yet, many variants of transfer RNA (tRNA) genes that induce amino acid misincorporation are found in human genomes. Mistranslation induces pleiotropic effects on proteostasis, ranging from protein misfolding to impaired protein biosynthesis and degradation. We employ Saccharomyces cerevisiae (budding yeast), a genetically and biochemically

We present CGeNArateWeb, a new web tool for the three-dimensional simulation of naked DNA and protein-bound chromatin fibers. The server allows the user to obtain a dynamic representation of long segments of linear, circular, or protein–DNA segments thanks to a Langevin dynamics coarse-grained (CG) model working with a machine-learning (ML) fitted C1′-resolution Hamiltonian. The CG trajectories can

Recent advances have significantly enriched our understanding of complex bacteria–phage interactions. To date, over one hundred bacterial antiphage systems have been identified, yet the mechanisms of many, including the recently discovered Menshen system, remain elusive. We employed comparative genomics and protein bioinformatics for a systematic investigation of the Menshen system, focusing on its

Aging is accompanied by widespread DNA methylation changes across the genome. While age-related methylation studies typically focus on individual CpGs, cluster analysis provides more robust data and improved interpretation. We characterized age-associated CpG-cluster methylation changes in mouse spleens, peripheral blood mononuclear cells, and livers. We identified a novel signature termed blanket

The genome structure fundamentally shapes bacterial physiology, ecology, and evolution. Though insertion sequences (IS) are known drivers of drastic evolutionary changes in the genome structure, the process is typically slow and challenging to observe in the laboratory. Here, we developed a system to accelerate IS-mediated genome structure evolution by introducing multiple copies of a high-activity

Antimicrobial resistance (AMR) remains a critical challenge in public health and research. AmrProfiler is a comprehensive tool with three specialized modules: identifying acquired AMR genes, resistance-associated mutations, and ribosomal RNA (rRNA) gene mutations across nearly 18 000 bacterial species. By integrating and refining data from established databases, it provides a robust framework for AMR

The Protein Data Bank (PDB) is the largest database of experimentally determined protein structures, containing more than 230 000 experimentally determined structures. The chemical reactivity of proteins is based on the electron density distribution, which is usually approximated by partial atomic charges. However, because of the size and high variability, there is not yet a universal and accurate

Nanopore sequencing allows identification of base modifications, such as methylation, directly from raw current data. Prevailing approaches, including deep learning (DL) methods, require training data covering all possible sequence contexts. These data can be prohibitively expensive or impossible to obtain for some modifications. Hence, research into DNA modifications focuses on the most prevalent

PLIP, the protein–ligand interaction profiler, analyses molecular interactions in protein structures. PLIP detects eight types of non-covalent interactions. Initially focused on small-molecule, DNA, and RNA interactions to a protein, the current release incorporates protein–protein interactions. We document the usefulness of this feature by comparing PLIP interactions of the cancer drug venetoclax

Parental experience can influence progeny behavior through gamete-mediated non-genetic inheritance, that is, mechanisms that do not involve changes in inherited DNA sequence. However, underlying mechanisms remain poorly understood in vertebrates, especially for maternal effects. Here, we use the medaka, a model fish species, to investigate the role of auts2a, the ortholog of human AUTS2, a gene repressed

The incidence and mortality of endometrial cancer (EC) is on the rise. Eighty-five percent of ECs depend on estrogen receptor alpha (ERα) for proliferation, but little is known about its transcriptional regulation in these tumors. We generate epigenomics, transcriptomics, and Hi-C datastreams in healthy and tumor endometrial tissues, identifying robust ERα reprogramming and profound alterations in