Biology subjects

Sudlow, L. C.

Publications and source records attributed to Sudlow, L. C..

3 recordsLinked to original sources

bioRxiv2026

thematicGO: A Keyword-Based Framework for Interpreting Gene Ontology Enrichment via Biological Themes

BackgroundGene Ontology (GO) enrichment analysis is a widely used approach for interpreting high-throughput transcriptomic and genomic data. However, conventional GO over-representation analyses typically yield long, redundant lists of enriched terms that are difficult to apply to biological problems and identify the most relevant biological pathways. ResultsWe present thematicGO, a customizable framework that organizes enriched GO terms into biological themes using a curated keyword-based matching strategy. In this approach, GO enrichment of differentially expressed genes is performed using the g:Profiler Application Programming Interface (API), followed by the score aggregation within each theme from contributing individual GO terms. Side-by-side interpretation against conventional GO annotation workflows demonstrates that thematicGO captures related biological outcomes but at the same time substantially reduces redundancy and improves readability. To enhance accessibility, we implemented an interactive, web-deployed graphical user interface (GUI) that enables users to upload gene lists and explore thematic enrichment results. ConclusionthematicGO simplifies functional enrichment analysis by bridging the gap between granular GO term outputs and higher-level biological interpretation using a theme concept, which can be especially useful for RNA-seq studies that identify differentially expressed genes. The new approach complements an orthogonal standard GO enrichment technique with transparent, theme-based aggregation and comparison against classical GO annotation approaches. thematicGO provides an easy, understandable, and reproducible tool for transcriptomic studies, particularly those involving RNA-seq data and complex biological responses.

bioinformatics↗

bioRxiv2024

Identification Drug Targets for Oxaliplatin-Induced Cardiotoxicity without affecting cancer treatment through Inter Variability Cross-Correlation Analysis (IVCCA)

The successful treatment of side effects of chemotherapy faces two major limitations: the need to avoid interfering with pathways essential for the cancer-destroying effects of the chemotherapy drug, and the need to avoid helping tumor progression through cancer promoting cellular pathways. To address these questions and identify new pathways and targets that satisfy these limitations, we have developed the bioinformatics tool Inter Variability Cross-Correlation Analysis (IVCCA). This tool calculates the cross-correlation of differentially expressed genes, analyzes their clusters, and compares them across a vast number of known pathways to identify the most relevant target(s). To demonstrate the utility of IVCCA, we applied this platform to RNA-seq data obtained from the hearts of the animal models with oxaliplatin-induced CTX. RNA-seq of the heart tissue from oxaliplatin treated mice identified 1744 differentially expressed genes with False Discovery Rate (FDR) less than 0.05 and fold change above 1.5 across nine samples. We compared the results against traditional gene enrichment analysis methods, revealing that IVCCA identified additional pathways potentially involved in CTX beyond those detected by conventional approaches. The newly identified pathways such as energy metabolism and several others represent promising target for therapeutic intervention against CTX, while preserving the efficacy of the chemotherapy treatment and avoiding tumor proliferation. Targeting these pathways is expected to mitigate the damaging effects of chemotherapy on cardiac tissues and improve patient outcomes by reducing the incidence of heart failure and other cardiovascular complications, ultimately enabling patients to complete their full course of chemotherapy with improved quality of life and survival rates.

bioinformatics↗

bioRxiv2023

Oxaliplatin-induced cardiotoxicity in mice is connected to the changes in energy metabolism in the heart tissue

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed for physiological parameters, ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the hearts energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation, amino acid metabolism, glycolysis, electron transport chain, and NAD synthesis pathway. At high accumulative doses of oxaliplatin, the heart shifts its metabolism from FAs to glycolysis and increases lactate production. It also leads to strong overexpression of genes in NAD synthesis pathways such as Nmrk2. Changes in gene expression associated with energy metabolic pathways can be used to develop diagnostic methods to detect oxaliplatin-induced cardiotoxicity early on as well as therapy to compensate for the energy deficit in the heart to prevent heart damage. Significance StatementThis study uncovers the detrimental impact of chronic oxaliplatin treatment on heart metabolism in mice, linking high accumulative dosages to cardiotoxicity and heart damage. By identifying significant changes in gene expression related to energy metabolic pathways, the findings pave the way for the development of diagnostic methods to detect oxaliplatin-induced cardiotoxicity at an early stage. Furthermore, these insights may inform the creation of therapies that compensate for the energy deficit in the heart, ultimately preventing heart damage and improving patient outcomes in cancer treatment.

pharmacology and toxicology↗