Biology subjects

Ralevski, A.

Publications and source records attributed to Ralevski, A..

3 recordsLinked to original sources

bioRxiv2024

Generating Biomedical Knowledge Graphs from Knowledge Bases, Registries, and Multiomic Data

As large clinical and multiomics datasets and knowledge resources accumulate, they need to be transformed into computable and actionable information to support automated reasoning. These datasets range from laboratory experiment results to electronic health records (EHRs). Barriers to accessibility and sharing of such datasets include diversity of content, size and privacy. Effective transformation of data into information requires harmonization of stakeholder goals, implementation, enforcement of standards regarding quality and completeness, and availability of resources for maintenance and updates. Systems such as the Biomedical Data Translator leverage knowledge graphs (KGs), structured and machine learning readable knowledge representation, to encode knowledge extracted through inference. We focus here on the transformation of data from multiomics datasets and EHRs into compact knowledge, represented in a KG data structure. We demonstrate this data transformation in the context of the Translator ecosystem, including clinical trials, drug approvals, cancer, wellness, and EHR data. These transformations preserve individual privacy. We provide access to the five resulting KGs through the Translator framework. We show examples of biomedical research questions supported by our KGs, and discuss issues arising from extracting biomedical knowledge from multiomics data.

bioinformatics↗

bioRxiv2023

Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with impaired kidney function.

Bowel movement frequency (BMF) has been linked to changes in the composition of the human gut microbiome and to many chronic conditions, like metabolic disorders, neurodegenerative diseases, chronic kidney disease (CKD), and other intestinal pathologies like irritable bowel syndrome and inflammatory bowel disease. Lower BMF (constipation) can lead to compromised intestinal barrier integrity and a switch from saccharolytic to proteolytic fermentation within the microbiota, giving rise to microbially-derived toxins that may make their way into circulation and cause damage to organ systems. However, the connections between BMF, gut microbial metabolism, and the early-stage development and progression of chronic disease remain underexplored. Here, we examined the phenotypic impact of BMF variation in a cohort of generally-healthy, community dwelling adults with detailed clinical, lifestyle, and multi-omic data. We showed significant differences in microbially-derived blood plasma metabolites, gut bacterial genera, clinical chemistries, and lifestyle factors across BMF groups that have been linked to inflammation, cardiometabolic health, liver function, and CKD severity and progression. We found that the higher plasma levels of 3-indoxyl sulfate (3-IS), a microbially-derived metabolite associated with constipation, was in turn negatively associated with estimated glomerular filtration rate (eGFR), a measure of kidney function. Causal mediation analysis revealed that the effect of BMF on eGFR was significantly mediated by 3-IS. Finally, we identify self-reported diet, lifestyle, and psychological factors associated with BMF variation, which indicate several common-sense strategies for mitigating constipation and diarrhea. Overall, we suggest that aberrant BMF is an underappreciated risk factor in the development of chronic diseases, even in otherwise healthy populations.

systems biology↗

bioRxiv2020

The mammalian CLU homolog FMT controls development and behavior in Arabidopsis

Mitochondria in animals are associated with development, as well as physiological and pathological behaviors. Several conserved mitochondrial genes exist between plants and higher eukaryotes. Yet, comparative mitochondrial function among plant and animal species is poorly understood. Here, we show that FMT (FRIENDLY MITOCHONDRIA) from Arabidopsis thaliana, a highly conserved homolog of the mammalian CLU (CLUSTERED MITOCHONDRIA) gene family encoding mitochondrial proteins associated with developmental alterations and adult physiological and pathological behaviors, affects whole plant morphology and development under salt stress and control conditions. FMT was found to regulate mitochondrial morphology and dynamics as well as germination, root length, and flowering time. Here, we show that it also affects leaf expansion growth, salt stress-responses and hyponasty. Strikingly, FMT impacted the speed of hyponasty with corresponding change in speed of locomotion of CLU heterozygous knockout mice. These observations indicate that homologous genes affect homologous functions in plants and animals offering the possibility to develop plant models for the study of mammalian behaviors.

plant biology↗