Biology subjects

Heck, K.

Publications and source records attributed to Heck, K..

3 recordsLinked to original sources

bioRxiv2026

ToxCastLite: A portable semantic evidence graph linking in vitro bioactivity, in vivo toxicity, and exposure-use context

MotivationThe ToxCast database is a valuable resource for computational toxicology and new approach methodologies (NAMs), but the approximately 100 GB MySQL distribution is difficult to use for portable local analysis and cross-domain evidence mining. Many practical questions concern chemicals, in vitro bioactivity, in vivo toxicological evidence, and exposure-relevant product-use context rather than raw database keys. ResultsWe present ToxCastLite, a portable semantic evidence-access system that combines assay-scoped SQLite databases with a compact RDF layer for GraphDB-based querying. The system streams large ToxCast/invitrodb MySQL dumps into curated SQLite profiles, reducing the footprint to approximately 3 GB for focused use cases such as developmental neurotoxicity. Dense numerical evidence, including concentration-response rows, remains in SQLite, while the RDF projection exposes linked semantic entities such as chemicals, assays, endpoints, model results, potency parameters (AC50), and MC6 quality flags. We further extend the graph with CPDat v4.0 product-use and functional-use evidence and ToxRefDB v3.0 in vivo toxicity evidence, including processed studies, point-of-departure records, effect summaries, and observation summaries. These layers are linked through DSSTox Substance Identifiers, enabling integrated queries across NAM bioactivity, curated animal-study evidence, and exposure/use context. A Streamlit prototype supports exploration through a locally deployed LLM that translates natural-language questions into SPARQL, grounded by a versioned RDF schema to reduce hallucination risk. Case studies in developmental neurotoxicity demonstrate how ToxCastLite identifies concordance between high-confidence in vitro DNT activity and positive in vivo apical evidence, detects in vitro DNT activity beyond available DNT-specific in vivo evidence, and prioritizes chemicals where NAM signals, ToxRefDB evidence, and CPDat product-use context intersect. For selected results, users can drill down from the semantic graph to the underlying SQLite records and retrieve concentration-response curves for expert inspection without manually writing SQL or SPARQL. AvailabilityProject website at toxcast-lite.github.io/. Contactarif.doenmez@iuf-duesseldorf.de

bioinformatics↗

bioRxiv2024

Temperature drives seagrass recovery across the Western North Atlantic

Climate-driven shifts in herbivores, temperature and nutrient runoff threaten coastal ecosystem resilience. However, our understanding of ecological resilience, particularly for foundation species, remains limited due to a rarity of field experiments that are conducted across appropriate spatial and temporal scales and that investigate multiple stressors. This study aimed to evaluate the resilience of a widespread tropical marine plant (turtlegrass) to disturbances across its geographic range and how this is impacted by environmental gradients in (a)biotic factors. We assessed the resilience (i.e. recovery) of turtlegrass to a simulated disturbance (complete above- and belowground biomass removal) over a year. Contrary to temperate studies, higher temperature generally enhanced seagrass recovery. While nutrients and light availability had minimal impact, combined high levels of nutrients and herbivore grazing (meso and megaherbivore) reduced aboveground recovery. Our results suggest that the resilience of some tropical species, especially in cooler subtropical waters, may initially increase with warming.

ecology↗

bioRxiv2019

Establishing the phenotypic basis of adherent-invasive Escherichia coli (AIEC) pathogenicity in intestinal inflammation

Background & AimsAdherent-invasive Escherichia coli (AIEC) are enriched in ileal Crohns disease patients and implicated in disease etiology. However, AIEC pathogenesis is poorly understood, and it is unclear if the expansion of these organisms contributes to inflammatory bowel disease (IBD). Questions also remain as to what extent the various in vitro phenotypes used to classify AIEC are pathologically relevant.\n\nMethodsWe utilized a combination of in vitro phenotyping and a murine model of intestinal inflammation to systematically relate AIEC phenotypes to pathogenicity for 30 mucosa-associated human-derived E. coli strains. In vitro assays used included survival/replication in and TNF- production by J774 macrophages as well as invasion/replication in Caco2 intestinal epithelial cells.\n\nResultsAIEC do not form a phenotypic group that is clearly separated from non-AIEC. However, E. coli strains displaying in vitro AIEC phenotypes caused, on average, more severe intestinal inflammation. Survival/replication of strains in J774 and Caco2 cells were positively correlated with disease in vivo, while adherence to Caco2 cells and TNF- production by J774 cells were not. Importantly, co-colonization with adherent non-AIEC strains ameliorated AIEC-mediated disease.\n\nConclusionOur findings do not support the existence of an AIEC pathovar that can be clearly separated from commensal E. coli. However, intracellular survival/replication phenotypes do contribute to murine intestinal inflammation, suggesting that the AIEC overgrowth observed in human IBD makes a causal contribution to disease. The ability to differentiate pathologically-relevant AIEC phenotypes from those that are not provides an important foundation for developing strategies to predict, diagnose and treat human IBD through characterizing and modulating patient E. coli populations.

microbiology↗