Publications

Guidelines for managing scientific data have been established under the FAIR principles, requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of "data", we argue that computational models, especially mechanistic models prevalent in medicine, physiology and systems biology, deserve a complementary...

Climate change forces species to adapt rapidly to avoid extinction. To directly observe rapid adaptation and extinction, we conducted synchronized evolution experiments with Arabidopsis thaliana in 30 locations across Western Europe, the Mediterranean, the Levant, and North America. Whole-genome pooled sequencing of ~70,000 surviving plants revealed repeatable allele frequency shifts in similar climates but divergent shifts across contrasting ones, indicating evolutionary adaptation. We...

Single-cell RNA sequencing (scRNA-seq) allows transcriptional profiling, and cell-type annotation of individual cells. However, sample preparation in typical scRNA-seq experiments often homogenizes the samples, thus spatial locations of individual cells are often lost. Although spatial transcriptomic techniques, such as in situ hybridization (ISH) or Slide-seq, can be used to measure gene expression in specific locations in samples, it remains a challenge to measure or infer expression level for...

Posterior fossa type A (PFA) ependymoma is an unusual infantile brain tumour with few known somatic mutations, thought to be driven by epigenetic mechanisms¹. PFA ependymoma has a markedly higher incidence and worse prognosis in male children than in female children². The mechanisms that underlie these sex differences are at present unknown. Here we show that the cellular hierarchy of PFA ependymoma is less differentiated in male individuals than it is in female individuals. In the normal...

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CONCLUSIONS: Our results demonstrate that glomeruli and their components undergo dramatic and often divergent stiffness changes following different types of injury. Interestingly, podocyte softening is a common manifestation of proteinuric kidney diseases, a phenomenon that is associated with inactivation of transcription co-factors that maintain normal podocyte structure and function.

The accumulation of per- and polyfluoroalkyl substances (PFAS) in human tissues is known. However, PFAS accumulation in the lung tissue of lung cancer patients remains unexplored. We examined the distribution of 26 PFAS in lung tissues and found a total concentration ranging from 0.75 to 368 ng/g, with perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) identified as predominant compounds. Perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs) were the most...

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To define and systematically characterize the human E3 ubiquitin ligase (E3) landscape, we generated the E3-ome, a compendium of E3s encoded by the human genome. The E3-ome integrates experimental data, bioinformatics, and published research, revealing 672 high-confidence E3s. We standardized E3 classifications to create a unified framework for annotation and comparative analysis. The E3-ome identified several previously unrecognized domains, motifs, E3 candidates, and relationships, expanding...

Artificial intelligence (AI) has the potential to transform health care; however, successful integration of AI into health care requires overcoming obstacles, such as biases in data and AI models, and addressing challenges in generating sufficient clinical evidence for deployment. In this Viewpoint, we present a community-based, actionable framework for responsible and ethical development, deployment, and integration of AI-based solutions in health care, emphasising bias mitigation and clinical...

CONCLUSION: Our findings demonstrate that inhibiting the TAMs-induced IGF1/PI3K/Zic1 signaling axis results in MB regression and chemosensitization. These results underscore the therapeutic potential of combining clinical CSF1R inhibitor with standard chemotherapy as an effective treatment strategy for SHH MB.

Metagenomes of lignocellulose-degrading microbial communities are reservoirs of carbohydrate-active enzymes relevant to biomass processing. Whereas several metagenomes of natural digestive systems have been sequenced, the current study analyses metagenomes originating from an industrial anaerobic digester that processes effluent from a cellulose pulp mill. Both 16S ribosomal DNA and metagenome sequences were obtained following anaerobic cultivation of the digester inoculum on cellulose and...

Müller glia arise from late-stage retinal progenitor cells (RPCs) as a distinct lineage that diverges from neurogenic trajectories. Here, we identify the maternally imprinted gene Plagl1 as a key transcriptional regulator of gliogenesis in the murine retina. Plagl1 is expressed during the RPC-to-glia transition and is dynamically regulated in Müller glia following injury. To define its developmental role, we analyzed Plagl1⁺/⁻pat null mutant retinas at postnatal day 7 (P7), when central retinal...

Clostridium kluyveri is a promising biocatalyst for producing medium-chain carboxylic acids (MCCAs) from waste-derived carbon via chain elongation. MCCAs are platform chemicals with diverse applications across agriculture, food, cosmetics, and fuels and could support tandem resource recovery and sustainable chemical production. However, host defense systems have hindered efforts to engineer C. kluyveri for improved product yields, control over chain length and selectivity, and production of...

CONCLUSIONS: In analyses of biomarkers and composite subtypes for prognosis studies such as in breast cancer, the use of compatible imputation models and penalization methods is recommended for MC modeling in samples with low event numbers and/or with covariate imbalance.

Breast cancer brain metastasis (BCBM) is a devastating disease with limited treatment options, largely due to the presence of the blood-brain barrier (BBB) in the central nervous system (CNS), and thus, the development of effective alternative therapies for BCBM remains a significant unmet clinical challenge. Herein, we found that monocytes, M2 macrophages, and adrenomedullin (AM) were abundantly present in human BCBM. Therefore, we innovatively proposed monocytes/macrophages as promising...

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a Cytosine-Adenosine-Guanine (CAG) repeat expansion in the Huntingtin (HTT) gene, with no disease-modifying therapies currently available. The precise molecular function of the HTT protein is unclear, and the lack of selective chemical tools has limited functional studies. We have identified and characterized macrocyclic peptide binders targeting HTT. These binders exhibit low-nanomolar affinity in vitro and engage...

BACKGROUND: Although severe maternal morbidity (SMM), such as severe hemorrhage and sepsis, can occur from conception to 6 weeks postpartum, most surveillance studies in Canada are restricted to intrapartum cases, with rates approximating 17 per 1000 births. We aimed to characterize the frequency of SMM from conception to 6 weeks postpartum and describe its associations with maternal and clinical characteristics.

CONCLUSION: MRI-based machine learning models may support noninvasive prediction of BRAF mutation status in pLGG. FLAIR is the best-predicting single sequence, but multisequence integration was associated with improved and more balanced performance. These findings support multisequence radiomics as a promising tool to guide precision treatment in pLGG, particularly when tissue sampling is not feasible.

CONCLUSIONS: This pooled analysis provides limited evidence of an association between occupational exposure to chlorinated solvents and lung cancer, though exposure-response trends were noted among exposed individuals.