SPACE: STRING proteins as complementary embeddings.

Motivation: Representation learning has revolutionized sequence-based prediction of protein function and subcellular localization. Protein networks are an important source of information complementary to sequences, but the use of protein networks has proven to be challenging in the context of machine learning, especially in a cross-species setting.

Results: We leveraged the STRING database of protein networks and orthology relations for 1,322 eukaryotes to generate network-based cross-species protein embeddings.

ESCMID workshop: Artificial Intelligence and Machine Learning in Medical Microbiology Diagnostics.

Rapid advancements in artificial intelligence (AI) and machine learning (ML) offer significant potential to transform medical microbiology diagnostics, improving pathogen identification, antimicrobial susceptibility prediction and outbreak detection. To address these opportunities and challenges, the ESCMID workshop, "Artificial Intelligence and Machine Learning in Medical Microbiology Diagnostics", was held in Zurich, Switzerland, from June 2-5, 2025. The course featured expert lectures, practical sessions and panel discussions covering foundational ML concepts and deep learning architectures, data interoperability, quality control processes, model development and validation strategies.

Multiomics approach to evaluating personalized biomarkers of allergen immunotherapy.

Recent advancements in genomics and "omic" technologies have ushered in a transformative era referred to as personalized or precision medicine. This innovative approach considers the unique genetic profiles of individuals, along with a range of variability factors, to devise tailored disease treatments and prevention strategies that cater to the distinct needs of each patient. Although the terms personalized medicine and precision medicine are frequently utilized interchangeably, it is essential to delineate the subtle distinctions between them.

Phylodynamic estimation of the within-host evolutionary rate of extended-spectrum beta-lactamase-producing Enterobacterales.

Despite their clinical relevance, the within-host evolution of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales is still poorly understood. To estimate the within-host evolutionary rates of ESBL-producing and species complex, we fitted phylodynamic models to genomic sequence data of longitudinally collected rectal swabs from 63 colonized hospital patients. We estimated an average within-host evolutionary rate of 7.

Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling.

Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets, forelimb anomalies, and variable heart and kidney defects. TAR syndrome is caused by mutations in RBM8A/Y14, a component of the exon junction complex. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown.

The Greatest Extinction Event in 66 Million Years? Contextualising Anthropogenic Extinctions.

Biological communities are changing rapidly in response to human activities, with the high rate of vertebrate species extinction leading many to propose that we are in the midst of a sixth mass extinction event. Five past mass extinction events have commonly been identified across the Phanerozoic, with the last occurring at the end of the Cretaceous, 66 million years ago (Ma). However, life on Earth has always changed and evolved, with most species ever to have existed now extinct.

Gene co-occurrence and its association with phage infectivity in bacterial pangenomes.

Phages infect bacteria and have recently re-emerged as a promising strategy to combat bacterial infections. However, there is a lack of methods to predict whether and why a particular phage can or cannot infect a bacterial strain based on their genome sequences. Understanding the complex interactions between phages and their bacterial hosts is thus of considerable interest.

Ancient genomes provide evidence of demographic shift to Slavic-associated groups in Moravia.

Background: The Slavs are a major ethnolinguistic group of Europe, yet the process that led to their formation remains disputed. As of the sixth century CE, people supposedly belonging to the Slavs populated the space between the Avar Khaganate in the Carpathian Basin, the Merovingian Frankish Empire to the West and the Balkan Peninsula to the South. Proposed theories to explain those events are, however, conceptually incompatible, as some invoke major population movements while others stress the continuity of local populations.

Preventing CpG hypermethylation in oocytes safeguards mouse development.

Except for regulatory CpG-island sequences, genomes of most mammalian cells are widely DNA-methylated. In oocytes, though, DNA methylation (DNAme) is largely confined to transcribed regions. The mechanisms restricting de novo DNAme in oocytes and their relevance thereof for zygotic genome activation and embryonic development are largely unknown.

Integrated control of cancer stemness by σ receptor in advanced prostate cancer.

Cancer stem cells (CSCs) are pervasively present in human cancers and have a fundamental role in treatment failure and disease recurrence. Identifying critical elements that sustain the CSC phenotype may lead to novel strategies for cancer treatment. Here, we provide evidence of an essential link between the σ receptor (σR), a ligand-regulated chaperone protein residing preferentially at the endoplasmic reticulum-mitochondria contact sites, and CSCs in castration-resistant prostate cancers (CRPCs).

Proteo-transcriptomic reprogramming and resource reallocation define the aging mammalian brain.

Brain aging is a major risk for neurodegeneration, yet the underlying molecular mechanisms remain poorly understood. Here we performed an integrative proteo-transcriptomic analysis of the aging mouse brain, uncovering molecular signatures of aging through the assessment of protein aggregation, mRNA relocalization, and comparative proteomics across eight models of premature aging and neurodegeneration. We identified dynamic changes in physiological aging highlighting differences in synaptic maintenance and energy-allocation.

The relative contribution of close-proximity contacts, shared classroom exposure and indoor air quality to respiratory virus transmission in schools.

Close-proximity interactions are considered a key risk factor for respiratory virus transmission, but their importance relative to shared space and air quality remains unclear. We conducted a six-week longitudinal study in a Swiss secondary school (67 students, aged 14-15). We detected 87 infections in saliva samples and recorded absences to identify plausible transmissions, excluding implausible ones through genomic analysis.

Coral anthozoan-specific opsins employ a novel chloride counterion for spectral tuning.

Animal opsins are G protein-coupled receptors that have evolved to sense light by covalently binding a retinal chromophore via a protonated (positively charged) Schiff base. A negatively charged amino acid in the opsin, acting as a counterion, stabilizes the proton on the Schiff base, which is essential for sensitivity to visible light. In this study, we investigate the spectroscopic properties of a unique class of opsins from a reef-building coral belonging to the anthozoan-specific opsin II group (ASO-II opsins), which intriguingly lack a counterion residue at any of established sites.

Multi-omic assessment of mRNA translation dynamics in liver cancer cell lines.

The limited correlation between mRNA and protein levels within cells highlighted the need to study mechanisms of translational control. To decipher the factors that determine the rates of individual steps in mRNA translation, machine learning approaches are currently applied to large libraries of synthetic constructs, whose properties are generally different from those of endogenous mRNAs. To fill this gap and thus enable the discovery of elements driving the translation of individual endogenous mRNAs, we here report steady-state and dynamic multi-omics data from human liver cancer cell lines, specifically (i) ribosome profiling data from unperturbed cells as well as following the block of translation initiation (ribosome run-off, to trace translation elongation), (ii) protein synthesis rates estimated by pulsed stable isotope labeled amino acids in cell culture (pSILAC), and (iii) mean ribosome load on individual mRNAs determined by mRNA sequencing of polysome fractions (polysome profiling).

Poultry farm density and proximity drive highly pathogenic avian influenza spread.

The continuous spread of highly pathogenic avian influenza H5 viruses poses significant challenges, particularly in regions with high poultry farm densities where conventional control measures are less effective. Using phylogeographic and phylodynamic tools, we analysed virus spread in southwestern France in 2020 and 2021, a region with recurrent outbreaks. Following a single introduction, the virus spread regionally, mostly affecting duck farms, with an average velocity of 10.

One-shot design of functional protein binders with BindCraft.

Protein-protein interactions are at the core of all key biological processes. However, the complexity of the structural features that determine protein-protein interactions makes their design challenging. Here we present BindCraft, an open-source and automated pipeline for de novo protein binder design with experimental success rates of 10-100%.

Characterizing influenza A virus lineages and clinically relevant mutations through high-coverage wastewater sequencing.

Influenza A virus poses significant public health challenges, causing seasonal outbreaks and pandemics. Its rapid evolution motivates continuous monitoring of circulating influenza genomes to inform vaccine and antiviral development. Wastewater-based surveillance offers an unbiased, cost-effective approach for genomic surveillance.

DelSIEVE: cell phylogeny modeling of single nucleotide variants and deletions from single-cell DNA sequencing data.

With rapid advancements in single-cell DNA sequencing (scDNA-seq), various computational methods have been developed to study evolution and call variants on single-cell level. However, modeling deletions remains challenging because they affect total coverage in ways that are difficult to distinguish from technical artifacts. We present DelSIEVE, a statistical method that infers cell phylogeny and single-nucleotide variants, accounting for deletions, from scDNA-seq data.

Clinical Presentation and Causes of Prosthesis-Related Hypersensitivity Reactions: An Analysis of 225 Patients.

Introduction: Between 10% and 20% of all prosthesis patients experience implant-related complications within 1-2 years following surgery. Hypersensitivity to components within the prosthesis is a possible cause of these complications.

Methods: This study aimed to investigate the characteristics of prosthesis-related hypersensitivity (PRH) and identify possible associated risk factors.

Unlocking the potential of PubMed Central supplementary data files.

Motivation: Biocuration workflows often rely on comprehensive literature searches for specific biological entities. However, standard search engines such as MEDLINE and PubMed Central provide an incomplete picture of the scientific literature because they do not index the increasing amount of valuable information published in supplementary data files. Over two years, we addressed this gap by systematically extracting text from a large proportion (85%) of these files, resulting in 35 million searchable documents.

Development of avian influenza A(H5) virus datasets for Nextclade enables rapid and accurate clade assignment.

The 2022 panzootic of highly pathogenic avian influenza (HPAI) A(H5) viruses has led to unprecedented transmission to multiple mammalian species. Avian influenza A viruses of the H5 subtype circulate globally among birds and are classified into distinct clades based on their haemagglutinin (HA) genetic sequences. Thus, the ability to accurately and rapidly assign clades to newly sequenced isolates is key to surveillance and outbreak response.

Whole Genome Sequencing Reveals How Plasticity and Genetic Differentiation Underlie Sympatric Morphs of Arctic Charr.

Salmonids have a remarkable ability to form sympatric morphs after postglacial colonisation of freshwater lakes. These morphs often differ in morphology, feeding and spawning behaviour. Here, we explored the genetic basis of morph differentiation in Arctic charr (n = 283) by first establishing a high-quality reference genome and then using this in whole genome sequencing of distinct morphs present in two Norwegian and two Icelandic lakes.

Systema: a framework for evaluating genetic perturbation response prediction beyond systematic variation.

Predicting transcriptional responses to genetic perturbations is challenging in functional genomics. While recent methods aim to infer effects of untested perturbations, their true predictive power remains unclear. Here, we show that current methods struggle to generalize beyond systematic variation, the consistent transcriptional differences between perturbed and control cells arising from selection biases or confounders.

Identification of malignant cells in single-cell transcriptomics data.

Single-cell transcriptomics has significantly advanced our ability to uncover the cellular heterogeneity of tumors. A key challenge in single-cell transcriptomics is identifying cancer cells and, in particular, distinguishing them from non-malignant cells of the same cell lineage. Focusing on features that can be measured by single-cell transcriptomics, this review explores the molecular aberrations of cancer cells and their observable readouts at the RNA level.

Model Quality Assessment for CASP16.

The CASP16 evaluation of model accuracy (EMA) experiment assessed the ability of predictors to estimate the accuracy of predicted models, with a particular emphasis on multimeric assemblies. Expanding on the CASP15 framework, CASP16 introduced a new evaluation mode (QMODE3) focused on selecting high-quality models from large-scale AlphaFold2-derived model pools generated by MassiveFold. Three primary evaluation tasks were therefore conducted: QMODE1 assessed global structure accuracy, QMODE2 focused on the accuracy of interface residues, and QMODE3 tested model selection performance.