Biology subjects

Gocke, A.

Publications and source records attributed to Gocke, A..

4 recordsLinked to original sources

bioRxiv2025

OmixLitMiner 2: Guided Literature Mining Tools for Automated Categorization of Marker Candidates in Omics Studies

Omics analyses are crucial for understanding molecular mechanisms in biological research. The vast quantity of detected biomolecules presents a significant challenge in identifying potential biomarkers. Traditional methods rely heavily on labor-intensive literature mining to extract meaningful insights from long lists of regulated candidates. To address this, we developed OmixLitMiner 2 to improve the efficiency of omics data interpretation, increase the speed for the validation of results and accelerate further evaluation based on the selection of marker candidates for subsequent experiments. The updated tool utilizes UniProt for synonym and protein name retrieval and employs the PubMed database as well as PubTator 3.0 for mining abstracts and full texts of available biomedical literature. It allows for advanced keyword-based searches and provides classification of proteins or genes with respect to their awareness level in relationship to scientific questions. OmixLitMiner 2 offers improved functionality over the previous version and comes with a user-friendly Google Colab interface. In comparison to the previous version OmixLitMiner 2 improves the retrieval and classification of relevant publications. The tool significantly reduces the time required for manual searches, as demonstrated in a case study involving proteomic data from spatially resolved mouse brain cortex layers. Statement of SignificanceWe developed OmixLitMiner 2 to determine, for a given set of marker candidates, the extent to which they have been described in the literature. The tool is easy-to-use and can quickly generate a categorized list of references obtained by automated literature searches for protein and gene names and involving keywords related to a specific scientific question. The categorization provides a ranking of how well-studied the genes or proteins: Candidates of category 1 are well-known regarding the scientific question; Candidates of category 2 have been mentioned in a publication associated with the specific scientific question; Candidates of category 3 have never been described to be associated with the specific scientific question; Candidates of category 4 are not yet known proteins and are not associated with a gene name. This classification can aid in the decision, which protein or gene candidates to choose for follow-up experiments.

bioinformatics↗

bioRxiv2024

Co-activation of LIN28A and CTNNB1 disturbs cortical neuronal migration and pia mater integrity

Developmental signalling pathways act in stage and tissue dependent relation and mis-activation can drive tumour formation. The RNA-binding protein LIN28A maintains stemness and is overexpressed in embryonal brain tumours. Activating mutations of CTNNB1 - the WNT pathway effector - have been reported in respective brain tumours. The aim of this study was to investigate the interplay of these oncogenic proteins during embryonal brain development. The combination of both oncogenic factors did not lead to brain tumour formation but resulted in disturbed lamination and impaired cell migration in the cerebral cortex. Spatially resolved proteome analysis revealed imbalances of the extracellular matrix protein LAMB1 and its receptors RPSA and ITGB1 accompanied by a porous pial border and overmigration of neural cells. Cajal-Retzius cells were misplaced in deeper cortex regions without affecting general REELIN levels and additional reduced levels of -DYSTROGLYCAN. Taken together, the interplay of LIN28A and CTNNB1 resulted in a cortical migration disorder showing histomorphological and molecular similarities to human Cobblestone lissencephaly (type 2), highlighting novel implications of the oncogene LIN28A in extracellular matrix integrity.

neuroscience↗

bioRxiv2023

Assay for characterizing adsorption-properties of surfaces (APS) sample preparation prior to quantitative omics

Analytes during their journey from their natural sources to their identification and quantification are prone to adsorption to surfaces before they enter an analytical instrument, causing false quantities. This problem is especially severe in diverse omics. Here, thousands of analytes with a broad range of chemical properties and thus different affinities to surfaces are quantified within a single analytical run. For quantifying adsorption effects caused by surfaces of sample handling tools, an assay was developed, applying LC-MS/MS-based differential bottom-up proteomics and as probe a reference mixture of thousands of tryptic peptides, covering a broad range of chemical properties. The assay was tested by investigating the adsorption properties of several vials composed of polypropylene, including low-protein-binding polypropylene vials, borosilicate glass vials and low-retention glass vials. In total 3531 different peptides were identified and quantified across all samples and therefore used as probes. A significant number of hydrophobic peptides adsorbed on polypropylene vials. In contrast, only very few peptides adsorbed to low-protein-binding polypropylene vials. The highest number of peptides adsorbed to glass vials, driven by electrostatic as well as hydrophobic interactions. Calculation of the impact of the adsorption of peptides on differential quantitative proteomics showed significant false results. In summary, the new assay is suitable to characterize adsorption properties of surfaces getting into contact with analytes during sample preparation, thereby giving the opportunity to find parameters for minimizing false quantities. Insert Table of Contents artwork here O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/551632v3_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@bafb12org.highwire.dtl.DTLVardef@1b98219org.highwire.dtl.DTLVardef@c3b45org.highwire.dtl.DTLVardef@1074180_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2023

Cystatin C loaded in brain-derived extracellular vesicles rescues synapses after ischemic insult in vitro and in vivo

Synaptic loss is an early event in the undersupplied but not yet irreversibly injured penumbra area after an ischemic stroke. Promoting synaptic preservation in this area would likely improve functional neurological recovery. In the present study, we aimed to detect proteins involved in endogenous protection mechanisms of synapses in the penumbra after stroke and to analyse the potential beneficial effect of these candidates for a prospective stroke treatment. For this, we performed Liquid Chromatography coupled to Mass Spectrometry (LC-MS)-based proteomics of synaptosomes isolated from the ipsilateral hemispheres of mice subjected to experimental stroke at different time points (24 h, 4 and 7 days) and compared them to sham-operated mice. Proteomic analyses indicated that among the differentially expressed proteins between the two groups, cystatin C (CysC) was significantly increased at 24 h and 4 days following stroke, before returning to steady-state levels at 7 days, thus indicating a potential transient and intrinsic rescue mechanism attempt of neurons. When CysC was applied to primary neuronal cultures subjected to an in vitro model of ischemic damage, this treatment significantly improved the preservation of synaptic structures. Notably, similar effects were observed when CysC was loaded into brain-derived extracellular vesicles (BDEVs). Finally, when CysC contained in BDEVs was administered intracerebroventricularly to stroked mice, it significantly increased the expression of synaptic markers such as SNAP25, Homer-1, and NCAM in the penumbra area compared to the group supplied with empty BDEVs. Thus, we show that CysC-loaded BDEVs promote synaptic protection after ischemic damage in vitro and in vivo, opening the possibility of a therapeutic use in stroke patients.

neuroscience↗