Young, female and scientist: exploring barriers, challenges and opportunities.

Different societal, systemic and personal barriers exist at various stages along a female researcher's career that can potentially undermine their success. The equation for women to reach higher positions in STEM is a multivariable one, and while there has been considerable progress towards addressing some of these compared with the past, current solutions are inadequate and do not address all facets. Here, we asked female winners of the FEBS Open Bio poster prize about their experiences regarding barriers they have faced at the predoctoral and postdoctoral stages, their opinions on how these can be addressed and their advice to new students entering a PhD degree.

YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates.

We recently characterized the potent antiplasmodial activity of the aggregated protein dye YAT2150, whose presumed mode of action is the inhibition of protein aggregation in the malaria parasite. Using single-dose and ramping methods, assays were done to select Plasmodium falciparum parasites resistant to YAT2150 concentrations ranging from 3× to 0.25× the in vitro IC of the compound (in the two-digit nM range) and performed a cross-resistance assessment in P.

Evaluation of controls, quality control assays, and protocol optimisations for PacBio HiFi sequencing on diverse and challenging samples.

The Darwin Tree of Life (DToL) project aims to generate high-quality reference genomes for all eukaryotic organisms in Britain and Ireland. At the time of writing, PacBio HiFi reads are generated for all samples using the Sequel IIe systems by the Wellcome Sanger Institute's Scientific Operations teams, however we expect lessons from this work to apply directly to the Revio system too, as core principles of SMRT sequencing remain the same. We observed that HiFi yield is highly variable for DToL samples.

Dynamic co-evolution of transposable elements and the piRNA pathway in African cichlid fishes.

Background: East African cichlid fishes have diversified in an explosive fashion, but the (epi)genetic basis of the phenotypic diversity of these fishes remains largely unknown. Although transposable elements (TEs) have been associated with phenotypic variation in cichlids, little is known about their transcriptional activity and epigenetic silencing. We set out to bridge this gap and to understand the interactions between TEs and their cichlid hosts.

Conference report of the 2024 Antimicrobial Resistance Meeting.

The Antimicrobial Resistance - Genomes, Big Data and Emerging Technologies Conference explored key topics including measuring the burden of AMR, global public health pathogen genomics infrastructure and surveillance, translation and implementation of genomics for AMR control, use of techniques such as wastewater surveillance, mathematical and statistical modelling, and Artificial Intelligence (AI) to aid understanding of AMR. This report describes research presented during plenary sessions and discussions, keynote presentations and posters.

Cohort profile: the BangladEsh Longitudinal Investigation of Emerging Vascular and nonvascular Events (BELIEVE) cohort study.

Purpose: Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases (NCDs) in recent decades. There is, however, limited evidence about multidimensional determinants of NCDs in this population. The BangladEsh Longitudinal Investigation of Emerging Vascular and nonvascular Events (BELIEVE) study is a household-based prospective cohort study established to investigate biological, behavioural, environmental and broader determinants of NCDs.

Exome sequencing of UK birth cohorts.

Birth cohort studies involve repeated surveys of large numbers of individuals from birth and throughout their lives. They collect information useful for a wide range of life course research domains, and biological samples which can be used to derive data from an increasing collection of omic technologies. This rich source of longitudinal data, when combined with genomic data, offers the scientific community valuable insights ranging from population genetics to applications across the social sciences.

Exploring the experiences of minoritised groups at life sciences conferences in the UK: new perspectives and actions to improve inclusivity in the sector.

Attending and participating in scientific research meetings and conferences is a key mechanism for researchers to share information and knowledge, build networks, and establish relationships and collaborations to support career development. In the UK, researchers from minoritised or underrepresented groups, may have a different experience at a conference than their peers. As a high profile provider of genomics-focussed life science conferences, Wellcome Connecting Science is committed to ensuring that our events are as inclusive as possible.

An exploration of unusual antimicrobial resistance phenotypes in Salmonella Typhi from Blantyre, Malawi reveals the ongoing role of IncHI1 plasmids.

Typhoid fever is a significant public health problem endemic in Southeast Asia and Sub-Saharan Africa. Antimicrobial treatment of typhoid is however threatened by the increasing prevalence of antimicrobial resistant (AMR) Typhi, especially in the globally successful lineage (4.3.

Large-scale evaluation of outcomes after a genetic diagnosis in children with severe developmental disorders.

Purpose: We sought to evaluate outcomes for clinical management after a genetic diagnosis from the Deciphering Developmental Disorders study.

Methods: Individuals in the Deciphering Developmental Disorders study who had a pathogenic/likely pathogenic genotype in the DECIPHER database were selected for inclusion ( = 5010). Clinical notes from regional clinical genetics services notes were reviewed to assess predefined clinical outcomes relating to interventions, prenatal choices, and information provision.

TopoQual polishes circular consensus sequencing data and accurately predicts quality scores.

Background: Pacific Biosciences (PacBio) circular consensus sequencing (CCS), also known as high fidelity (HiFi) technology, has revolutionized modern genomics by producing long (10 + kb) and highly accurate reads. This is achieved by sequencing circularized DNA molecules multiple times and combining them into a consensus sequence. Currently, the accuracy and quality value estimation provided by HiFi technology are more than sufficient for applications such as genome assembly and germline variant calling.

A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease.

Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant. AT2 dysfunction underlies many lung diseases, including interstitial lung disease (ILD), in which some inherited forms result from the mislocalization of surfactant protein C (SFTPC) variants. Lung disease modeling and dissection of the underlying mechanisms remain challenging due to complexities in deriving and maintaining human AT2 cells ex vivo.

Prolonged persistence of mutagenic DNA lesions in somatic cells.

DNA is subject to continual damage, leaving each cell with thousands of individual DNA lesions at any given moment. The efficiency of DNA repair means that most known classes of lesion have a half-life of minutes to hours, but the extent to which DNA damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising from 818 DNA lesions that persisted across multiple cell cycles in normal human stem cells from blood, liver and bronchial epithelium.

Conventional and regionally distinctive risk factors for first-onset myocardial infarction: the Bangladesh Risk of Acute Vascular Events (BRAVE) case-control study.

Background: South Asians may be particularly susceptible to premature myocardial infarction (MI) owing both to conventional cardiovascular risk factors and practices distinctive to South Asia. Identifying modifiable risk factors for MI in these populations could inform prevention strategies. We have, therefore, studied conventional risk factors and other characteristics in relation to occurrence of first MI in Bangladesh.

The mutational landscape of Staphylococcus aureus during colonisation.

Staphylococcus aureus is an important human pathogen and a commensal of the human nose and skin. Survival and persistence during colonisation are likely major drivers of S. aureus evolution.

Implementing Mutational Epidemiology on a Global Scale: Lessons from Mutographs.

The Mutographs Cancer Grand Challenge team aimed to discover unknown causes of cancer through mutational epidemiology, an alliance of cancer epidemiology and somatic genomics. By generating whole-genome sequences from thousands of cancers and normal tissues from more than 30 countries on five continents, it discovered unsuspected mutagenic exposures affecting millions of people, raised the possibility that some carcinogens act by altering forces of selection in tissue microenvironments rather than by mutagenesis, and demonstrated changes to the direction of somatic evolution in normal cells of the human body in response to exogenous exposures and noncancer diseases. See related article by Bressan et al.

Typing of feces-derived Candida albicans strains using a novel seven-locus microsatellite panel reveals associations with yeast phenotype in individuals with inflammatory bowel disease.

Inflammatory diseases of the human gastrointestinal tract are affected by the microbes that reside in the mucosal surfaces. Patients with inflammatory bowel diseases (IBD) have altered bacterial and fungal intestinal compositions, including higher levels of fecal Candida yeasts. Ongoing research indicates that genetic and phenotypic diversity of Candida albicans may be linked with disease severity.

Emerging carbapenem-resistant in a tertiary care hospital in Lima, Peru.

The emergence of carbapenem-resistant (CRKP) poses a significant public health threat, particularly in low- and middle-income countries (LMICs) with limited surveillance and treatment options. This study examines the genetic diversity, resistance patterns, and transmission dynamics of 66 CRKP isolates recovered over 5 years (2015-2019) after the first case of CRKP was identified at a tertiary care hospital in Lima, Peru. Our findings reveal a shift from to as the dominant carbapenemase gene after 2017.

Nuclear and mitochondrial genome assemblies for the endangered wood-decaying fungus Somion occarium.

Somion occarium is a wood-decaying bracket fungus belonging to an order known to be rich in useful chemical compounds. Despite its widespread distribution, S. occarium has been assessed as endangered on at least one national Red List, presumably due to loss of old-growth forest habitat.

A scalable variational inference approach for increased mixed-model association power.

The rapid growth of modern biobanks is creating new opportunities for large-scale genome-wide association studies (GWASs) and the analysis of complex traits. However, performing GWASs on millions of samples often leads to trade-offs between computational efficiency and statistical power, reducing the benefits of large-scale data collection efforts. We developed Quickdraws, a method that increases association power in quantitative and binary traits without sacrificing computational efficiency, leveraging a spike-and-slab prior on variant effects, stochastic variational inference and graphics processing unit acceleration.

A Complete Assembly and Annotation of the American Shad Genome Yields Insights into the Origins of Diadromy.

Transitions across ecological boundaries, such as those separating freshwater from the sea, are major drivers of phenotypic innovation and biodiversity. Despite their importance to evolutionary history, we know little about the mechanisms by which such transitions are accomplished. To help shed light on these mechanisms, we generated the first high-quality, near-complete assembly and annotation of the genome of the American shad (Alosa sapidissima), an ancestrally diadromous (migratory between salinities) fish in the order Clupeiformes of major cultural and historical significance.

Site-saturation mutagenesis of 500 human protein domains.

Missense variants that change the amino acid sequences of proteins cause one-third of human genetic diseases. Tens of millions of missense variants exist in the current human population, and the vast majority of these have unknown functional consequences. Here we present a large-scale experimental analysis of human missense variants across many different proteins.

Predicting cell morphological responses to perturbations using generative modeling.

Advancements in high-throughput screenings enable the exploration of rich phenotypic readouts through high-content microscopy, expediting the development of phenotype-based drug discovery. However, analyzing large and complex high-content imaging screenings remains challenging due to incomplete sampling of perturbations and the presence of technical variations between experiments. To tackle these shortcomings, we present IMage Perturbation Autoencoder (IMPA), a generative style-transfer model predicting morphological changes of perturbations across genetic and chemical interventions.

Chromosome-level echidna genome illuminates evolution of multiple sex chromosome system in monotremes.

Background: A thorough analysis of genome evolution is fundamental for biodiversity understanding. The iconic monotremes (platypus and echidna) feature extraordinary biology. However, they also exhibit rearrangements in several chromosomes, especially in the sex chromosome chain.