Biology subjects

Monzo, C.

Publications and source records attributed to Monzo, C..

5 recordsLinked to original sources

bioRxiv2026

SQANTI-browser: visualization and curation of SQANTI3-classified long-read transcriptomes within the UCSC Genome Browser

Long-read sequencing enables transcriptome-wide isoform discovery. However, it generates substantial technical and structural ambiguity that complicates transcript interpretation. Here, we present SQANTI-browser, a classification-aware visualization framework that converts SQANTI3 outputs into interactive UCSC Genome Browser Track Hubs, preserving full transcript structural metadata. By integrating SQANTI classifications directly within the UCSC ecosystem, SQANTI-browser enables dynamic filtering and evidence-guided curation alongside public resource tracks. Furthermore, its adaptive architecture natively supports non-reference genomes, orthogonal data, and custom metadata fields. Applied to clinical, noisy, and synthetic datasets, SQANTI-browser resolves alignment artifacts and rescues actionable novel isoforms, providing a robust framework for long-read transcriptome curation.

bioinformatics↗

bioRxiv2025

To join or not to join: handling biological replicates in long-read RNA sequencing data

Long-read RNA sequencing (lrRNA-seq) has revolutionized transcriptomics facilitating the study of alternative splicing and resulting in identification of thousands of novel transcripts. While isoform identification has received significant attention, the handling of biologically replicated lrRNA-seq datasets remains less explored. However, how multiple samples are combined in a lrRNA-seq study may strongly impact transcript identification. This study defines and evaluates two strategies for obtaining consensus transcriptomes from multi-sample lrRNA-seq data: "Join & Call", where reads from all samples are combined before transcript identification, and "Call & Join", where transcript identification is performed on individual samples before combining the resulting annotations. We applied these strategies to a highly replicated dataset of mouse brain and kidney tissues, using both PacBio and ONT technologies, across six widely used transcript reconstruction tools. Our results indicate that the optimal strategy depends on the chosen computational tool and research objective. We found that Join & Call is generally more suitable for discovering rarely occurring, novel isoforms, as pooling evidence increases confidence in calling lowly-expressed transcripts. Conversely, Call & Join is computationally more efficient and often preferable for highly replicated datasets when the investigation of rare novel transcripts is not the primary objective. Our findings provide a conceptual and practical framework for multi-sample transcriptome reconstruction, guiding best practices in the context of increasingly large-scale lrRNA-seq studies.

bioinformatics↗

bioRxiv2024

SQANTI-reads: a tool for the quality assessment of long read data in multi-sample lrRNA-seq experiments.

SQANTI-reads leverages SQANTI3, a tool for the analysis of the quality of transcript models, to develop a read-level quality control framework for replicated long-read RNA-seq experiments. The number and distribution of reads, as well as the number and distribution of unique junction chains (transcript splicing patterns), in SQANTI3 structural categories are informative of raw data quality. Multi-sample visualizations of QC metrics are presented by experimental design factors to identify outliers. We introduce new metrics for 1) the identification of potentially under-annotated genes and putative novel transcripts and for 2) quantifying variation in junction donors and acceptors. We applied SQANTI-reads to two different datasets, a Drosophila developmental experiment and a multi-platform dataset from the LRGASP project and demonstrate that the tool effectively reveals the impact of read coverage on data quality, and readily identifies strong and weak splicing sites. SQANTI-reads is open source and available for download at GitHub.

bioinformatics↗

bioRxiv2024

A combination of the geroprotectors trametinib and rapamycin is more effective than either drug alone

Genetic suppression of activity of the insulin/IGF/mTORC1/Ras network can ameliorate the effects of ageing in animals. The network provides multiple drug targets because of its role in metabolic disease and cancer, and these are candidates for repurposing for geroprotection. For instance, inhibition of the activity of the mTORC1 complex by rapamycin can extend lifespan in multiple organisms including mice, with early indications of efficacy in humans. Trametinib inhibits MEKs in the Ras pathway and can extend lifespan in Drosophila. However, it is not yet known if trametinib alone or in combination with rapamycin can extend mouse lifespan or improve health at older ages. We assessed survival and health indices of female and male mice treated with trametinib or rapamycin alone, or with the two in combination at the same doses. Trametinib treatment extended lifespan in both sexes, while its combination with rapamycin caused further, additive prolongation. Combination treatment reduced liver tumours in both sexes and spleen tumours in males, and ameliorated the age-related increase in brain glucose uptake. There was a striking reduction in inflammation in the brain, kidney, spleen and muscle with combination treatment, accompanied by reduced circulating levels of pro-inflammatory cytokines. Trametinib alone is therefore geroprotective in mice, but combined trametinib and rapamycin treatment is more geroprotective than treatment with either drug alone, suggesting immediate translational potential for humans.

physiology↗

bioRxiv2023

Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases

Proteolytic cell surface release ( shedding) of the prion protein (PrP), a broadly expressed GPI-anchored glycoprotein, by the metalloprotease ADAM10 impacts on neurodegenerative and other diseases in animal and in vitro models. Recent studies employing the latter also suggest shed PrP (sPrP) to be a ligand in intercellular communication and critically involved in PrP-associated physiological tasks. Although expectedly an evolutionary conserved event, and while soluble forms of PrP are present in human tissues and body fluids, neither proteolytic PrP shedding and its cleavage site nor involvement of ADAM10 or the biological relevance of this process have been demonstrated for the human body thus far. In this study, cleavage site prediction and generation (plus detailed characterization) of sPrP-specific antibodies enabled us to identify PrP cleaved at tyrosin 226 as the physiological and strictly ADAM10-dependent shed form in humans. Using cell lines, neural stem cells and brain organoids, we show that shedding of human PrP can be stimulated by PrP-binding ligands without targeting the protease, which may open novel therapeutic perspectives. Site-specific antibodies directed against human sPrP also detect the shed form in brains of cattle, sheep and deer, hence in all most relevant species naturally affected by fatal and transmissible prion diseases. In human and animal prion diseases, but also in patients with Alzheimers disease, sPrP relocalizes from a physiological diffuse tissue pattern to intimately associate with extracellular aggregates of misfolded proteins characteristic for the respective pathological condition. Findings and research tools presented here will accelerate novel insight into the roles of PrP shedding (as a process) and sPrP (as a released factor) in neurodegeneration and beyond.

neuroscience↗