Biology subjects

Alber, S.

Publications and source records attributed to Alber, S..

5 recordsLinked to original sources

bioRxiv2026

High-resolution analysis of T cell subsets, clonality, and trajectories in psoriasis

Psoriasis is sustained by type 17 immunity, yet how transcriptionally defined T-cell states are clonally organized across lesions, clinically uninvolved skin, and the circulation remains incompletely understood. We performed paired single-cell RNA and T-cell receptor (TCR) sequencing of T cells isolated from two spatially separated lesions, non-lesional skin, and peripheral blood from 23 participants with psoriasis, together with healthy skin and blood comparators. We resolved 19 cutaneous T-cell populations and found that lesions were enriched for IL-17-associated CD4+ and CD8+ states and activated regulatory T-cell states. CD8+ Tc17 cells showed prominent clonal expansion, and expanded clonotypes contributed more prominently to skin than to blood. Clonotype sharing was greatest between paired lesions, while clonotypes detected in cutaneous IL-17-associated cells mapped to multiple circulating phenotypes, indicating that blood and skin capture complementary features of the disease-associated repertoire. At the sample level, T-cell composition separated 57 lesional samples into two recurrent compositional states that were largely concordant across paired body sites. HLA-C*06:02 status was associated with differences in pretreatment lesional CD8+ T-cell composition, clonotype overlap, and clonal-size distributions. Exploratory longitudinal analyses in eight treated participants showed heterogeneous remodeling of T-cell composition and clonotype detection after therapy. Together, these findings define tissue-restricted and tissue-shared features of the psoriatic T-cell repertoire and identify clonal architecture across skin sites and blood as an organizing feature of lesion heterogeneity.

immunology↗

bioRxiv2025

CellVoyager: AI CompBio Agent Generates New Insights by Autonomously Analyzing Biological Data

Modern biology increasingly relies on complex, high dimensional datasets such as single-cell RNA sequencing (scRNA-seq). However, the richness of such data means that conventional analyses may only scratch its surface. Extracting meaningful insights from these datasets often requires advanced computational methods and domain expertise. Current AI agents for biology are primarily focused on executing user-specified commands and are therefore limited by the users creativity and familiarity with which kinds of analyses are useful. Furthermore, these agents do not account for prior analyses already attempted by researchers, reducing their ability to build upon existing work. To address these limitations, we introduce CellVoyager, an AI agent that autonomously explores scRNA-seq datasets in novel directions conditioned on prior user-ran analyses. Built on large language models, CellVoyager ingests both the dataset and a record of prior analyses to generate and test new hypotheses within a Jupyter notebook environment. We evaluate CellVoyager on CellBench, a new benchmark based on 50 published scRNA-seq studies encompassing 483 analyses. Given only the background sections of these papers, CellVoyager outperformed GPT-4o and o3-mini by up to 20% in predicting which analyses the authors eventually conducted. We then carried out three in-depth case studies where CellVoyager is given previously published papers with their scRNA-seq datasets and conducts analyses to generate new findings. The original authors of each study evaluated these findings and consistently rated them as creative and sound; 80% of the agents hypotheses were deemed scientifically interesting. For example, in one case study, the agent found that CD8+ T cells in COVID-19 infection are more primed for pyroptosis, which was not explored by the original researchers. CellVoyager also reanalyzed a brain aging dataset to discover a previously unreported association between increased transcriptional noise and aging in the subventricular zone of the brain. These results demonstrate that CellVoyager can act both autonomously and collaboratively to accelerate hypothesis generation and computational biology. It also highlights the potential of agents like CellVoyager to unlock new biological insights by reanalyzing the vast existing biological data at scale.

bioinformatics↗

bioRxiv2022

Targeting of the human nasal microbiota by secretory IgA antibodies

The human nasal microbiome is critical for health and disease, since it is associated with the occurrence of respiratory disorders and hosting of opportunistic pathogens. The host therefore protects this vulnerable mucosal barrier from infection and maintains homeostasis of the microbiota through various mechanisms, including the production of secretory IgA (sIgA) antibodies. However, we currently lack a comprehensive understanding of how sIgA affects the nasal microbiota. Through IgA-seq analysis of nasal microbiome samples and sIgA deposition experiments using nasal sIgA from healthy volunteers, we identified which bacterial genera and species are targeted by sIgA on the level of the individual host. We observed that the amount of sIgA secreted into the nasal mucosa by the host varied substantially and was negatively correlated with the bacterial density. The interaction between mucosal sIgA antibodies and the nasal microbiome was highly individual, and was not dependent on the microbiome composition, or the age or gender of the host. Importantly, we showed that for the clinically relevant opportunistic pathogen S. aureus, sIgA reactivity was in part the result of epitope-independent interaction of sIgA with the antibody binding protein SpA through binding of sIgA Fab regions. This study thereby offers a first comprehensive insight of targeting of nasal microbiota by sIgA antibodies, which may help to better understand the shaping and homeostasis of the nasal microbiome by the host and offer new targets for intervention in disease-associated microbiota.

microbiology↗

bioRxiv2022

A new monoclonal antibody enables BAR analysis of subcellular importin β1 interactomes

Importin {beta}1 (KPNB1) is a nucleocytoplasmic transport factor with critical roles in both cytoplasmic and nucleocytoplasmic transport, hence there is keen interest in the characterization of its subcellular interactomes. We found limited efficiency of BioID in detection of importin complex cargos, and therefore generated a highly specific and sensitive anti-KPNB1 monoclonal antibody to enable Biotinylation by Antibody Recognition (BAR) analysis of importin {beta}1 interactomes. The monoclonal antibody recognizes an epitope comprising residues 301-320 of human KPBN1, and strikingly is highly specific for cytoplasmic KPNB1 in diverse applications, with little or no reaction with KPNB1 in the nucleus. BAR with this novel antibody revealed numerous new interactors of importin {beta}1, expanding the KPNB1 interactome to cytoplasmic and signaling complexes that highlight potential new functions for the importins complex beyond nucleocytoplasmic transport. Data are available via ProteomeXchange with identifier PXD032728.

neuroscience↗

bioRxiv2020

PTBP1 Regulates Injury Responses and Sensory Pathways in Adult Peripheral Neurons

Polypyrimidine Tract Binding Protein 1 (PTBP1) is expressed only at embryonic stages in central neurons. Its downregulation triggers neuronal differentiation in precursor and non-neuronal cells, an approach recently used to generate neurons de novo for amelioration of neurodegenerative disorders. Moreover, PTBP1 is replaced by its paralog PTBP2 in mature central neurons. Surprisingly, we found both proteins co-expressed in adult sensory and motor neurons, with PTBP2 restricted mainly to the nucleus, while PTBP1 shows strong axonal localization. Levels of axonal PTBP1 increased markedly after peripheral nerve injury, and its cargos include mRNAs involved in axonal growth and regeneration, such as importin {beta}1 and RhoA. Perturbation of PTBP1 affects neuronal injury responses, axon outgrowth and sensation in vivo. Thus, PTBP1 has roles in sensory function and regenerative capacity of adult sensory neurons. These findings suggest that caution may be required before considering targeting PTBP1 for therapeutic purposes.

neuroscience↗