Biology subjects

Ahola, V.

Publications and source records attributed to Ahola, V..

5 recordsLinked to original sources

bioRxiv2026

Modeling healthy proteomic profiles for anomaly detection using subspace learning based one-class classification

High-throughput plasma proteomics provides sensitive and scalable measurements of thousands of systemic protein profiles from minimally invasive blood samples, creating new opportunities for disease detection and population-scale health monitoring. However, robust statistical modeling remains challenging due to high dimensionality, limited availability and high diversity of diseased samples, resulting in class imbalance in clinical cohorts. Here, we present a subspace One-Class Classification (OCC) framework for proteomics-driven anomaly detection that models healthy proteomic profiles as a reference distribution. To address the limitations of conventional hyperparameter tuning in severely imbalanced data settings, we introduce a fully data-driven parameter estimation strategy that infers all model parameters directly from intrinsic properties of the healthy training data, without using any disease labels. Using plasma proteomics data generated with Olink, we evaluate a family of subspace and graph-embedded subspace extensions of Support Vector Data Description, in which all models operate on learned low-dimensional representations rather than the original feature space. Models are trained exclusively on a healthy reference cohort and evaluated on heterogeneous disease conditions, including multiple cancer types and an independent COVID-19 cohort, with all disease samples withheld from training to enable unbiased assessment of cross-disease generalization. Across disease contexts, the evaluated one-class models yield stable and balanced detection performance, demonstrating that learning structured low-dimensional representations of healthy proteomic variation captures intrinsic biological organization that generalizes across disease-specific perturbations. These results establish healthy-profile-based, subspace one-class learning as a robust and disease-agnostic framework for screening in high-dimensional plasma proteomics.

bioinformatics↗

bioRxiv2026

Sex-linked dilution colour in the European domestic goose confirmed to be a 1-bp deletion in the Melan-A gene

Plumage colour in domestic geese is an important economic trait and a selection target since the early days of domestication. In European domestic geese of greylag goose (Anser anser) origin, white plumage colour is known to be caused by two independent loci, one causing white spotting and one causing sex-linked dilution, together producing white plumage. Strong candidate mutations have been identified upstream of the EDNRB2/LOC106047519 gene (endothelin receptor B-like) and within the sex-linked MLANA gene (melan-A). To confirm these candidate mutations, we genotyped differently coloured European domestic goose breeds, wild greylag geese, Chinese domestic geese (derived from swan goose A. cygnoid) and European and Chinese domestic geese crossbreeds. One base pair deletion in the MLANA gene (NW_013185876.1: g.950,868 C > -) was confirmed to cause sex-linked dilution, and thus autosexing (almost white gander and goose diluted grey). However, mutation upstream of EDNRB2/LOC106047519 (NW_013185915.1: g. 775,151 G > T) was not the causative mutation for saddleback pattern but strongly linked to it in European domestic geese. We sequenced the EDNRB2 gene and coding sequence of a neighbouring VAMP7 gene (vesicle-associated membrane protein 7) but found no genetic variaion linked to colour. Additionally, we sequenced the coding sequence of TYRP1 (tyrosinase related protein 1), a candidate gene for buff colouration, but no variation linked to colour was found. Further, we genotyped a 14-bp insertion in exon 3 of the EDNRB2 gene, known to be causative of the white phenotype in the Chinese domestic goose, and identified it in one European domestic goose individual.

genetics↗

bioRxiv2024

Muller glia cell cycle re-activation by simultaneous cyclin D1 overexpression and p27kip1 knockdown promotes retinal regeneration in mice

Harnessing the regenerative potential of endogenous stem cells to restore lost neurons is a promising strategy for treating neurodegenerative disorders. Muller glia (MG), the primary glial cell type in the retina, exhibit extraordinary regenerative abilities in zebrafish, proliferating and differentiating into neurons post-injury. However, the regenerative potential of mouse MG is limited by their inherent inability to re-enter the cell cycle, constrained by high levels of the cell cycle inhibitor p27Kip1 and low levels of cyclin D1. Here, we report a method to drive robust MG proliferation by adeno-associated virus (AAV)-mediated cyclin D1 overexpression and p27Kip1 knockdown. MG proliferation induced by this dual targeting vector was self-limiting, as MG did not undergo uncontrolled proliferation. As shown by single-cell RNA-sequencing, cell cycle reactivation led to suppression of interferon signaling, activation of reactive gliosis, and downregulation of glial genes in MG. Over time, the majority of the MG daughter cells retained the glial fate, resulting in an expanded MG pool. Interestingly, about 1% MG daughter cells expressed markers for retinal interneurons, suggesting latent neurogenic potential in a small MG subset. By establishing a safe, controlled method to promote MG proliferation in vivo while preserving retinal integrity, this work provides a valuable tool for combinatorial therapies integrating neurogenic stimuli to promote neuron regeneration.

neuroscience↗

bioRxiv2024

Single-nuclei histone modification profiling of the adult human central nervous system unveils epigenetic memory of developmental programs

The adult human central nervous system (CNS) is remarkably complex, with neural cells displaying extensive transcriptional heterogeneity. However, how different layers of epigenetic regulation underpin this heterogeneity is poorly understood. Here, we profile the adult human CNS from distinct regions, for chromatin accessibility at the single-nuclei level. In addition, we simultaneously co-profiled the histone modifications H3K27me3 and H3K27ac at the single nuclei-level, providing their first map in all major human CNS cell types. We unveil primed chromatin signatures at HOX loci in spinal cord-derived human oligodendroglia (OLG) but not microglia. These signatures were reminiscent of developmental OLG but were decoupled from robust gene expression. Moreover, using high-resolution Micro-C, we show that induced pluripotent stem cell (iPS) derived human OLGs exhibit a HOX chromatin architecture compatible with the primed chromatin in adult OLGs, and bears a strong resemblance not only to OLG developmental architecture, but also high-grade pontine gliomas. Thus, adult OLG retain epigenetic memory from developmental states, which might enable them to promptly transcribe Hox genes, in contexts of regeneration, but also make them susceptible to gliomagenesis.

neuroscience↗

bioRxiv2020

Improved chromosome level genome assembly of the Glanville fritillary butterfly (Melitaea cinxia) based on SMRT Sequencing and linkage map.

The Glanville fritillary (Melitaea cinxia) butterfly is a long-term model system for metapopulation dynamics research in fragmented landscapes. Here, we provide a chromosome level assembly of the butterflys genome produced from Pacific Biosciences sequencing of a pool of males, combined with a linkage map from population crosses. The final assembly size of 484 Mb is an increase of 94 Mb on the previously published genome. Estimation of the completeness of the genome with BUSCO, indicates that the genome contains 93 - 95% of the BUSCO genes in complete and single copies. We predicted 14,830 gene models using the MAKER pipeline and manually curated 1,232 of these gene models. The genome and its annotated gene models are a valuable resource for future comparative genomics, molecular biology, transcriptome and genetics studies on this species.

genomics↗