Biology subjects

Kurtz, S.

Publications and source records attributed to Kurtz, S..

7 recordsLinked to original sources

bioRxiv2026

CyChat: a conversational Cytoscape app for no-code, reproducible network analysis

Network-based analyses of molecular interactions are useful for interpreting high-throughput omics data and identifying therapeutic targets. Cytoscape is the standard platform for these tasks, but users face a trade-off between accessible graphical workflows that are difficult to document and reproducible automation in Python or R that requires programming expertise. General-purpose coding assistants can generate Cytoscape Automation scripts, but remain external to Cytoscape. We present CyChat, a Cytoscape Desktop app that integrates a chat interface and a large language model (LLM) agent into the application. CyChat translates natural language into executable Cytoscape Automation workflows, runs generated Python code, and exports chat sessions with executed code as standalone Jupyter notebooks. To reduce setup barriers, CyChat includes an embedded Python runtime and supports both cloud-based and locally hosted LLMs. CyChat was evaluated across ten Cytoscape workflows using seven LLM providers, each represented by one LLM. The strongest configuration achieves a pass rate above 99%. In a qualitative evaluation based on a published network visualization, CyChat completes the task in 1.5-5 minutes, compared with 15-20 minutes for manual GUI workflows by computational biologists. CyChat is available through the Cytoscape App Store at https://apps.cytoscape.org/apps/cychat.

bioinformatics↗

bioRxiv2026

Genomic analyses demonstrate the absence of genetic sex determination in the dioecious conifer Taxus baccata

Hundreds of plant lineages have independently evolved dioecy, i.e., separation of female and male flowers on different individuals. In all dioecious plants investigated at the molecular level to date, sex is determined genetically through a sex-determining region (SDR). SDRs have mostly been studied in angiosperms, although dioecy is relatively more common among gymnosperms. Here, we investigate sex determination in the gymnosperm Taxus baccata. We assembled four haplotype-resolved chromosome-level genomes for one female and one male tree, with an average size of 10.04 Gb, and generated resequencing data for 100 phenotypically sexed individuals. Strikingly, k-mer analyses, genome-wide association studies and differential coverage analyses demonstrate the absence of an SDR in the T. baccata genome. This indicates a non-genetic mechanism of sex determination, most likely via a sex-specific epiallele. Given that T. baccata is the first species studied among a large group of conifers, our findings suggest that such a mechanism might be widespread.

plant biology↗

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

The power and limits of predicting exon-exon interactions using protein 3D structures

Alternative splicing (AS) effects on cellular functions can be captured by studying changes in the underlying protein-protein interactions (PPIs). Because AS results in the gain or loss of exons, existing methods for predicting AS-related PPI changes utilize known PPI interfacing exon-exon interactions (EEIs), which only cover [~]5% of known human PPIs. Hence, there is a need to extend the existing limited EEI knowledge to advance the functional understanding of AS. In this study, we explore whether existing computational PPI interface prediction (PPIIP) methods, originally designed to predict residue-residue interactions (RRIs), can be used to predict EEIs. We evaluate three recent state-of-the-art PPIIP methods for the RRI- as well as EEI-prediction tasks using known protein complex structures, covering [~]230,000 RRIs and [~]27,000 EEIs. Our results provide the first evidence that existing PPIIP methods can be extended for the EEI prediction task, showing F-score, precision, and recall performances of up to [~]38%, [~]63%, and [~]28%, respectively, with a false discovery rate of less than 5%. Our study provides insights into the power and limits of existing PPIIP methods to predict EEIs, thus guiding future developments of computational methods for the EEI prediction task. We provide streamlined computational pipelines integrating each of the three considered PPIIP methods for the EEI prediction task to be utilized by the scientific community.

bioinformatics↗

bioRxiv2023

Systems genetics uncover new loci containing functional gene candidates in Mycobacterium tuberculosis-infected Diversity Outbred mice.

Mycobacterium tuberculosis, the bacillus that causes tuberculosis (TB), infects 2 billion people across the globe, and results in 8-9 million new TB cases and 1-1.5 million deaths each year. Most patients have no known genetic basis that predisposes them to disease. We investigated the complex genetic basis of pulmonary TB by modelling human genetic diversity with the Diversity Outbred mouse population. When infected with M. tuberculosis, one-third develop early onset, rapidly progressive, necrotizing granulomas and succumb within 60 days. The remaining develop non-necrotizing granulomas and survive longer than 60 days. Genetic mapping using clinical indicators of disease, granuloma histopathological features, and immune response traits identified five new loci on mouse chromosomes 1, 2, 4, 16 and three previously identified loci on chromosomes 3 and 17. Quantitative trait loci (QTLs) on chromosomes 1, 16, and 17, associated with multiple correlated traits and had similar patterns of allele effects, suggesting these QTLs contain important genetic regulators of responses to M. tuberculosis. To narrow the list of candidate genes in QTLs, we used a machine learning strategy that integrated gene expression signatures from lungs of M. tuberculosis-infected Diversity Outbred mice with gene interaction networks, generating functional scores. The scores were then used to rank candidates for each mapped trait in each locus, resulting in 11 candidates: Ncf2, Fam20b, S100a8, S100a9, Itgb5, Fstl1, Zbtb20, Ddr1, Ier3, Vegfa, and Zfp318. Importantly, all 11 candidates have roles in infection, inflammation, cell migration, extracellular matrix remodeling, or intracellular signaling. Further, all candidates contain single nucleotide polymorphisms (SNPs), and some but not all SNPs were predicted to have deleterious consequences on protein functions. Multiple methods were used for validation including (i) a statistical method that showed Diversity Outbred mice carrying PWH/PhJ alleles on chromosome 17 QTL have shorter survival; (ii) quantification of S100A8 protein levels, confirming predicted allele effects; and (iii) infection of C57BL/6 mice deficient for the S100a8 gene. Overall, this work demonstrates that systems genetics using Diversity Outbred mice can identify new (and known) QTLs and new functionally relevant gene candidates that may be major regulators of granuloma necrosis and acute inflammation in pulmonary TB.

genetics↗

bioRxiv2023

Monitoring lasting changes to brain tissue integrity through mechanical properties following adolescent exercise intervention in a rat model of Fetal Alcohol Spectrum Disorders

BackgroundFetal Alcohol Spectrum Disorders (FASD) encompass a group of highly prevalent conditions resulting from prenatal alcohol exposure. Alcohol exposure during the third trimester of pregnancy overlapping with the brain growth spurt is detrimental to white matter growth and myelination, particularly in the corpus callosum, ultimately affecting tissue integrity in adolescence. Traditional neuroimaging techniques have been essential for assessing neurodevelopment in affected youth; however, these methods are limited in their capacity to track subtle microstructural alterations to white matter, thus restricting their effectiveness in monitoring therapeutic intervention. In this preliminary study we use a highly sensitive and clinically translatable Magnetic Resonance Elastography (MRE) protocol for assessing brain tissue microstructure through its mechanical properties following an exercise intervention in a rat model of FASD. MethodsRat pups were divided into two groups: alcohol-exposed (AE) pups which received alcohol in milk substitute (5.25 g/kg/day) via intragastric intubation on postnatal days (PD) four through nine during the rat brain growth spurt (Dobbing and Sands, 1979), or sham-intubated (SI) controls. In adolescence, on PD 30, half AE and SI rats were randomly assigned to either a modified home cage with free access to a running wheel or to a new home cage for 12 days (Gursky and Klintsova, 2017). Previous studies conducted in the lab have shown that 12 days of voluntary exercise intervention in adolescence immediately ameliorated callosal myelination in AE rats (Milbocker et al., 2022, 2023). MRE was used to measure longitudinal changes to mechanical properties of the whole brain and the corpus callosum at intervention termination and one-month post-intervention. Histological quantification of precursor and myelinating oligoglia in corpus callosum was performed one-month post-intervention. ResultsPrior to intervention, AE rats had lower forebrain stiffness in adolescence compared to SI controls (p = 0.02). Exercise intervention immediately mitigated this effect in AE rats, resulting in higher forebrain stiffness post-intervention in adolescence. Similarly, we discovered that forebrain damping ratio was lowest in AE rats in adolescence (p < 0.01), irrespective of intervention exposure. One-month post-intervention in adulthood, AE and SI rats exhibited comparable forebrain stiffness and damping ratio (p > 0.05). Taken together, these MRE data suggest that adolescent exercise intervention supports neurodevelopmental "catch-up" in AE rats. Analysis of the stiffness and damping ratio of the body of corpus callosum revealed that these measures increased with age. Finally, histological quantification of myelinating oligodendrocytes one-month post-intervention revealed a negative rebound effect of exercise cessation on the total estimate of these cells in the body of corpus callosum, irrespective of treatment group which was not convergent with noninvasive MRE measures. ConclusionsThis is the first application of MRE to measure changes in brain mechanical properties in a rodent model of FASD. MRE successfully captured alcohol-related changes to forebrain stiffness and damping ratio in adolescence. These preliminary findings expand upon results from previous studies which used traditional diffusion neuroimaging to identify structural changes to the adolescent brain in rodent models of FASD (Milbocker et al., 2022; Newville et al., 2017). Additionally, in vivo MRE identified an exercise-related alteration to forebrain stiffness that occurred in adolescence, immediately post-intervention.

bioengineering↗

bioRxiv2019

The knockout of the HMG-Domain of the porcine SRY-gene by CRISPR/Cas RNP microinjection causes sex reversal in gene-edited pigs

1The sex-determining region on the Y chromosome (SRY) is thought to be the central genetic element of male sex development. Mutations within the SRY gene are associated with a male-to-female sex reversal syndrome in humans and other mammalian species such as mice and rabbits. However, the underlying mechanisms are largely unknown. To understand the biological function of the SRY gene, a site-directed mutational analysis is required to investigate associated phenotypic changes at the molecular, cellular and morphological level. In our study, we successfully generated a knockout of the porcine SRY gene by microinjection of two clustered regularly interspaced short palindromic repeats (CRISPR) - associated protein - 9 nuclease (Cas9) ribonucleoprotein (RNP) complexes targeting the centrally located "high mobility group" (HMG) domain of the SRY gene. Mutations within this region resulted in the development of complete external and internal female genitalia in genetically male pigs. The internal female genitalia including uteri, ovaries, and oviducts, revealed substantial size differences in 9-months old SRY-knockout pigs compared to age-matched female wild type controls. In contrast, a deletion within the 5 flanking region of the HMG domain was not associated with sex reversal. Results of this study demonstrates for the first time the central role of the HMG domain of the SRY gene in male sex determination in pigs. Moreover, quantitative analysis by digital PCR revealed evidence for a duplication of the porcine SRY locus. Our results pave the way towards the generation of boars exclusively producing phenotypically female offspring to avoid surgical castration without anesthesia in piglets. Moreover, the study establishes a large animal model that is much more similar to humans in regard of physiology and anatomy and pivotal for longitudinal studies.

developmental biology↗