Biology subjects

Leinonen, H. O.

Publications and source records attributed to Leinonen, H. O..

4 recordsLinked to original sources

bioRxiv2026

CoTRA: an integrated R/Shiny framework for transparent bulk and single-cell RNA-seq analysis

Bulk RNA-seq and single-cell RNA-seq (scRNA-seq) are widely used to investigate gene-expression changes, but downstream analysis often requires multiple statistical,visualization, and reporting tools, creating fragmented workflows that are difficult to configure and reproduce. We developed CoTRA (Comprehensive Toolbox for RNA-seq Analysis), an open-source R/Shiny package providing independent bulk and scRNA-seq workflows within a common graphical environment. CoTRA supports quality control, differential expression, annotation, enrichment, dimensionality reduction, clustering, marker detection, cell-type annotation, differential abundance, trajectory inference, pathway activity, cell-cell communication, and reporting while exposing key analytical parameters. Compared with 14 other platforms across 49 predefined criteria, CoTRA fully supported 46 and partially supported three. Under matched inputs and parameters, CoTRA reproduced direct DESeq2, edgeR, and Seurat implementations, including identical significant bulk gene sets and scRNA-seq clustering (ARI = 1.000; NMI = 1.000). Retinal case studies recapitulated degeneration-associated transcriptional changes and demonstrated cell-type-resolved analysis. Synthetic scRNA-seq benchmarking scaled to 50,000 cells with 5.10 GB peak memory. CoTRA v1.0.0 requires R [≥] 4.4.0, has been tested on Linux, Windows, and macOS, is GPL-3 licensed, and is available at https://github.com/UmairSeemab/CoTRA, and support is provided through GitHub Issues.

bioinformatics↗

bioRxiv2025

ODDB: Ocular Disease Database for integrated analysis of ocular disease gene drug relationships

Ocular diseases such as age-related macular degeneration, glaucoma, diabetic retinopathy, and inherited retinal dystrophies are leading causes of vision loss worldwide, yet existing databases often address only limited aspects of these disorders. To fill this gap, we developed the Ocular Disease Database (ODDB), a web-based resource that integrates genes, biomarkers, variants, and drugs associated to ocular diseases. Data were systematically collected through literature mining of PubMed-indexed journals, the NCBI Gene Expression Omnibus (GEO), and drug regulatory agency datasets. Multi-omics, experimental, and clinical information were harmonized using standardized integration workflows. The database is organized according to two complementary ontologies: one based on the anatomical site of pathology (cornea, retina, optic nerve) and another on gene inheritance pattern. ODDB currently covers over 170 ocular diseases, more than 1190 genes, 2400+ variants, and 386 drugs, including both approved and investigational compounds. Each record includes detailed annotations of associated genes, variants, therapeutic targets, and mechanisms of action. The platform supports interactive querying and network-based visualization of disease-gene-drug relationships. All data was internally validated for accuracy and are compliant with FAIR principles, ensuring accessibility and interoperability. ODDB (https://www.oculardiseases.fi/) provides a comprehensive and standardized reference for exploring molecular mechanisms and therapeutic opportunities in ocular diseases.

bioinformatics↗

bioRxiv2024

Organic opto-nanobiointerface enables multiscale biomodulation

Virtually all organic material on Earth has been produced converting solar energy through photosynthesis in chloroplasts, a sack-like, double membrane organelle in plants and algae, where transmembrane electron transfer occurs from lumen to stroma. Although animals hardly harness the power of photosynthesis, their bioelectrical signals extensively regulate complex electrophysiological behaviors, rendering it a superior target for biomedical innovation. Here, a crude structural mimicry of chloroplast has led us to discover that hollow sphere graphitic carbon nitride nanoparticles (hg-C3N4 NPs) endowed non-genetic, subcellular and intercellular photo-modulation of various excitable and non-excitable cells, accumulatively achieving modulation at tissue/organ function level. The homogeneous hg-C3N4 NPs showed responsiveness to light via both photoelectrochemical and photothermal mechanisms. The hg-C3N4 NPs can be spontaneously internalized with excellent cytocompatibility. Using a focusing laser, the hg-C3N4 NPs enable intracellular optical stimulation with subcellular resolution, inducing calcium transient release in multiple cells and propagation in primary cardiomyocytes and cardiac fibroblasts. At multicellular scale, optical pacing and synchronization of cardiomyocyte beating is readily achieved by LED. Further, we demonstrate that hg-C3N4 nanoparticles can be safely delivered into the mouse eye and elicit measurable cortical and behavioral light responses in a subset of animals in a model of advanced retinal degeneration. Finally, application of hg-C3N4 NPs to porcine retinal tissue ex vivo confirmed their modulation capability to directly activate RGCs activity under LED photostimulation. Taken together, these nanostructured biomimetic photocatalytic NPs offer high resolution, leadless optical probing, non-invasive delivery and great biocompatibility, serving as a versatile tool for addressing a range of complex biomedical challenges through subcellular, intercellular and tissue-level photo-modulation across a broad spectrum of scales.

bioengineering↗

bioRxiv2022

Visual system hyperexcitability and compromised V1 receptive field properties in early-stage retinitis pigmentosa in mice

Inherited retinal degenerative diseases are a prominent cause of blindness. Even though mutations causing death of photoreceptors are mostly known, the pathophysiology downstream in the inner retina and along the visual pathway is incompletely characterized in the earliest disease stages. Here we investigated retinal, midbrain and cortical visual function using electroretinography (ERG), the optomotor response (OMR), visual evoked potentials (VEPs), respectively, and single unit electrophysiology at the primary visual cortex (V1) in light-adapted juvenile ([~] 1-month-old) and young adult (3-month-old) RhoP23H/WT mice, representative of early-stage retinitis pigmentosa (RP). Photopic ERG revealed up to [~] 30 % hypersensitivity to light in RhoP23H/WT mice, as measured by the light intensity required to generate half-maximal b-wave (I50 parameter). RhoP23H/WT mice also showed increased optomotor responses towards low spatial frequency drifting gratings, indicative of visual overexcitation at the midbrain level. At the V1 level, VEPs and single-cell recordings revealed prominent hyperexcitability in the juvenile RhoP23H/WT mice. Mean VEP amplitudes for light ON stimuli were nearly doubled in 1-month-old RhoP23H/WT mice compared to controls, and more than doubled for light OFF. Single-cell recordings showed a significantly increased spontaneous V1 neuron firing in the RhoP23H/WT mice, and persistent contrast and temporal sensitivities. In contrast, direction selectivity was severely compromised. Our data suggest that during early RP, the visual pathway becomes hyperexcited. This could have both compensatory and deleterious consequences for visual behavior. Further studies on the mechanisms of hyperexcitability are warranted as this could lead to therapeutic interventions for RP. Significance statementLost retinal function in many blinding retinal degenerative disorders could soon be alleviated by advanced therapies that restore photoreception. However, it is unknown whether a visual system rewired downstream of the photoreceptors can process signals adequately. We studied the functional consequences of early rod death along the visual pathway in young retinitis pigmentosa (RP) mice. Photopic inner retina responses were moderately hypersensitized in the electroretinograms of RP mice. Reflex-based visual behavior and visual cortex electrophysiology showed hyperexcitability. Some aspects of complex visual processing were remarkably resistant to degeneration, whereas others were severely impacted. We conclude that the visual system adapts to lost photoreception by increasing sensitivity, but simultaneously becomes detrimentally hyperexcited. Mechanistic understanding could lead to therapeutic preservation and restoration of vision.

physiology↗