Biology subjects

Liguori, R.

Publications and source records attributed to Liguori, R..

6 recordsLinked to original sources

bioRxiv2026

Metadata Collector: An Open-Source Platform for Standardized Metadata Management in Multi Centre Sequencing Projects

BackgroundNext-generation sequencing (NGS) projects generate increasingly complex metadata that are critical for reproducibility, interoperability, and compliance with FAIR principles. Nevertheless, metadata curation in multi-institutional settings often still relies on spreadsheets, manual data entry and curation, as well as non-standardized terminology. These practices frequently result in incomplete or inconsistent annotations, hinder metadata sharing, and delay submission to public repositories. ResultsWe developed Metadata Collector as a React/API/PostgreSQL web platform and deployed it on a Kubernetes cluster within a large German research consortium. The platform implements a flexible, machine-readable metadata model for experimental data and integrates customizable templates, controlled vocabularies designed to support future ontology integration, and a complete event-based versioning model. Since deployment, Metadata Collector has been used across 32 projects involving RNA-seq, scRNA-seq, ATAC-seq and multiomics datasets, representing over 700 annotated samples contributed by multiple consortium partners. The platform is designed for use by non-computational researchers as well as centralized facilities and can be integrated into existing research data management infrastructures. ConclusionsMetadata Collector embeds standardization early in the metadata lifecycle, ensuring consistent, FAIR-aligned, and reproducible metadata across distributed research groups. Its modular, open-source architecture supports both local and consortium-scale deployments and provides a foundation for future extensions, including multi-omics support and integration with laboratory information management systems and automated submission pipelines. AvailabilityOpen-source under MIT license: https://github.com/spang-lab/metadata-collector Graphical abstract of Metadata Collector O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/730314v1_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@c7e913org.highwire.dtl.DTLVardef@9701acorg.highwire.dtl.DTLVardef@1eed3eborg.highwire.dtl.DTLVardef@9af69a_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

A novel CAR T cell blend targeting PDPN and GD2 to overcome glioblastoma heterogeneity

BackgroundWhile chimeric antigen receptor (CAR) T cells have achieved encouraging remission rates in hematological malignancies, they demonstrated limited success in treating Glioblastoma (GBM), particularly due to high intra- and intertumoral heterogeneity. In this study, we identified a relevant and preserved target antigen, Podoplanin (PDPN), and evaluated the potential of a PDPN- and GD2-CAR T cell blend to overcome GBM heterogeneity. MethodsTarget antigen screening included clinical samples, healthy tissues and cell lines, as well as publicly available RNA sequencing datasets. The anti-tumor function of CAR T cells were examined in co-culture experiments with GBM cell lines and patient-derived organoids (PDOs), and in vivo after locoregional delivery in orthotopic xenograft models. ResultsThe generated CAR T cells demonstrated strong anti-tumor activity against several cell lines and PDOs from multiple patients. PDPN and GD2 expression was detectable in all PDOs at varying densities and regardless of the antigenic profile, the CAR T cell blend induced significantly higher levels of apoptosis in organoids than single antigen targeting counterparts. In vivo, we observed efficient tumor regression after locoregional administration of monospecific CAR T cells. While heterogeneous orthotopic tumors eventually relapsed in these groups, blended therapy resulted in a significantly increased overall survival and even achieved cure in the majority of mice. ConclusionThis novel PDPN-/GD2-CAR T cell blend demonstrated strong efficacy in advanced preclinical models of glioblastoma. The results suggest that this approach can overcome GBM heterogeneity in clinical application and address previous limitations of single antigen CAR T cell therapies. KEYPOINTSO_LIPDPN is a relevant and consistent CAR T cell target antigen in primary and recurrent GBM C_LIO_LIPDPN- and GD2-CAR T cells display synergistic anti-tumor activity in patient-derived organoids C_LIO_LILocal delivery of our CAR T cell blend confers long-term survival and cure in GBM-bearing mice C_LI IMPORTANCE OF THE STUDYThe highly variable landscape of tumor antigens in GBM represents a serious obstacle to single antigen CAR T cell therapies. In this study, we identified Podoplanin (PDPN) and GD2 as the most preserved target antigens in a screening campaign, with an even increased density in recurrent GBM compared to primary GBM. We combined PDPN- and GD2-CAR T cells in a blended treatment approach to counter antigen heterogeneity, and achieved a substantial gain in efficacy against patient-derived organoids (PDOs). In an orthotopic xenograft model, locoregional administration of the PDPN- and GD2-CAR T cell blend conferred long-term complete remission and increased survival compared to single antigen targeting. This study provides a hierarchy of CAR target antigens for treating GBM and illustrates the therapeutic potential of combinatorial antigen targeting using a PDPN/GD2-CAR T cell blend. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/636223v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@109a9aaorg.highwire.dtl.DTLVardef@16215faorg.highwire.dtl.DTLVardef@910623org.highwire.dtl.DTLVardef@129f79c_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGRAPHICAL ABSTRACT:C_FLOATNO C_FIG

immunology↗

bioRxiv2024

Macrophages foster adaptive anti-tumor immunity by ZEB1-dependent cytotoxic T cell chemoattraction

Tumor-associated macrophages (TAMs) shape the tumor microenvironment (TME) and exert a decisive impact on anti-tumor immunity. Understanding TAM function is therefore critical to understand anti-tumor immune responses and to design immunotherapies. Here, we describe the transcription factor ZEB1, a well-known driver of epithelial-to-mesenchymal transition, as an intrinsic regulator of TAM function in adaptive anti-tumor immunity. By combining cell type-specific deletion of Zeb1 with syngeneic models of colorectal and pancreatic cancer, we discovered an unexpected function of ZEB1 in the TAM-mediated control of T cell trafficking. ZEB1 supports secretion of a subset of chemokines including CCL2 and CCL22 by promoting their transcription and translation as well as by safeguarding protein processing. ZEB1 thereby elevates cytotoxic T cell (CTL) recruitment in vitro and in vivo and fosters immunosurveillance during tumor as well as lung metastatic outgrowth. Our study spotlights ZEB1 as a crucial facilitator of adaptive anti-tumor immunity and uncovers a potential therapeutic window of opportunity for cytokine-guided enhancement of CTL infiltration into tumors and metastases.

cancer biology↗

bioRxiv2023

Seeding Activity of Skin Misfolded Tau as a Novel Biomarker for Tauopathies

Tauopathies are a group of age-related neurodegenerative diseases with a molecular hallmark of the prion-like propagation and accumulation of pathologically phosphorylated tau protein in the brain. They include Alzheimers disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Picks disease (PiD). Currently, in the peripheral tissues and body fluids there are no reliable diagnostic biomarkers available that are able to directly reflect the capability of propagation and spreading of the misfolded tau aggregates. Here, we revealed significantly increased amounts of phosphorylated tau in the skin of AD patients compared to those in other tauopathies and normal controls. Moreover, the seed-amplification assay (SAA) by the ultrasensitive real-time quaking-induced conversion (RT-QuIC) displayed that the prion-like seeding activity of pathological tau in the skin of cadavers with neuropathologically confirmed tauopathies including AD, PSP, CBD, PiD was dramatically higher than that in normal controls, yielding 75-80% sensitivity and 95-100% specificity, respectively, depending on different tau substrates used. The increased tau-seeding activity was also observed in biopsy skin samples from living AD and PSP patients. Moreover, analysis of the end products of skin-tau SAA confirmed that the increased seeding activity is accompanied with formation of tau aggregates that are of different physicochemical properties determined by the different tau-substrates used. Our study provides proof-of-concept that the skin tau-SAA can differentiate tauopathies from normal controls, suggesting that the seeding activity of the skin misfolded tau can serve as an accurate diagnostic biomarker of tauopathies.

neuroscience↗

bioRxiv2021

Biomass, microbial composition and functions are responsible for the differential removal of trace organic chemicals in biofiltration systems

Biofiltration processes help to remove trace organic chemicals (TOrCs) both in wastewater and drinking water treatment systems. However, the detailed TOrCs biotransformation mechanisms as well as the underlying drivers behind the variability of site specific transformation processes remain elusive. In this study, we used laboratory batch incubations to investigate the biotransformation of 51 TOrCs in eight bioactive filter materials of different origins treating a range of waters, from wastewater effluents to drinking water. Microscopy, 16S rRNA amplicon and whole metagenome sequencing for assessing associations between the biotransformation rate constants, microbial composition and genetic potential complemented chemical analysis. We observed strong differences in the mean global removal of TOrCs between the individual sand filters (-1.4% to 58%), which were mirrored in overall biomass, microbial community composition, and enzyme encoding genes. From the six investigated biomass markers, ATP turned out to be a major predictor of the mean global biotransformation rate, while compound specific biotransformations were correlated with the microbial community composition. High biomass ecosystems were indicated in our systems by a dominance of Nitrospirae, but individual TOrC biotransformation was statistically connected to rare taxa (< 2%) such as Hydrogenophaga, or indiviudal functions such as the enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase encoding genes. In general, this study provides new insights into so far rarely addressed variability of TOrCs biotransformation. We propose novel biological indicators for the removal performance of TOrCs in biofiltration systems, highlighting the role of living biomass in predicting and normalizing the global transformation, and the role of the microbial community for the individual transformation of TOrCs in engineered and natural systems. Contribution to the Field StatementTrace organic chemicals (TOrCs) are an emerging problem in the aquatic environment that has attracted global attention over the last decade. Recent research efforts on this topic have increased our knowledge on the transformation of TOrCs and various technologies have been developed to improve their removal. In this study, we investigated a wide range of biotransformation of TOrCs by eight sand filter materials from wastewater and water treatment plants. Biotransformation rate constants were calculated using first-order kinetics to evaluate TOrC removal performance. We reevaluated the role of biomass and could thus explain a greater part of the global TOrC removal performance. The remaining variation in removal rates of individual compounds correlated with the microbiome of the biofilter. Rare biosphere lineages and specific enzyme categories genes were correlated with the removal of certain compounds. In summary, our research identified future indicators for successful biotransformation of TOrCs in biofilter systems.

microbiology↗

bioRxiv2021

Microbial retention and resistances in stormwater quality improvement devices treating road runoff

Current knowledge about the microbial communities that occur in in urban road runoff is scarce. Road runoff of trafficked roads can be heavily polluted and is treated by stormwater quality improvement devices (SQIDs). However, microbes may influence the treatment process of these devices or could lead to stress resistant opportunistic microbial strains. In this study, the microbial community in the influent, effluent and the filter materials for the removal of dissolved heavy metals of two different SQIDs were analyzed to determine the microbial load, retention, composition, and mobile resistance genes. Although the microbes were replaced by new taxa in the effluent, there was no major retention of microbial genera. Further, the bacterial abundance of the SQIDs effluent was relatively stable over time. The heavy metal content correlated with intl1 and with microbial genera. The filter media itself was enriched with Intl1 gene cassettes, carrying several heavy metal and multidrug resistance genes (e.g. czrA, czcA, silP, mexW and mexI), indicating that this is a hot spot for horizontal gene transfer. Overall, the results shed light on road runoff microbial communities, and pointed to distinct bacterial communities within the SQIDs, which subsequently influence the microbial community and the genes released with the treated water.

microbiology↗