Search bioRxiv⌕ Search

Biology subjects

Lingasamy, P.

Publications and source records attributed to Lingasamy, P..

2 recordsLinked to original sources

OncoProExp: An Interactive Shiny Web Application for Comprehensive Cancer Proteomics and Phosphoproteomics Analysis

Cancer research has been revolutionized by mass spectrometry (MS)-based proteomics, enabling large-scale profiling of proteins and post-translational modifications (PTMs) to identify critical alterations in cancer signaling pathways. However, the lack of comprehensive, userfriendly platforms for integrative analysis limits efficient data exploration, biomarker identification, and translational insights. To address this gap, we developed OncoProExp, a Shiny-based interactive web application designed for in-depth exploration of cancer proteomes and phosphoproteomes. OncoProExp offers robust workflows for data preprocessing, including missing value imputation and statistical filtering. The platform features interactive visualizations such as principal component analysis (PCA), hierarchical clustering heatmaps, and gene set enrichment analysis (GSEA), enabling detailed functional annotation. Differential expression analysis to identify differentially expressed proteins (DEPs) and phosphoproteins (DEPPs) facilitating the discovery of potential biomarkers and therapeutic targets. The application supports survival analysis and pan-cancer exploration using clinical and proteome/phosphoproteomic datasets. OncoProExp incorporates state-of-the-art predictive modeling using machine learning algorithms, including Support Vector Machines (SVMs), Random Forests, and Artificial Neural Networks (ANNs) for cancer risk stratification, achieving near-perfect accuracy in multi-cancer and single-cancer classification. These models are enhanced by SHapley Additive exPlanations (SHAP) for interpretability. To enhance its translational utility, the platform supports user-uploaded data and enables protein-protein interaction analysis, pathway enrichment analysis, cancer drug relevance evaluation, and clinical annotation using curated cancer-specific datasets. OncoProExp is deployable via Docker containers, ensuring flexible and scalable integration into individual servers. Its utility has been demonstrated using Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets, showcasing its potential to advance cancer biomarker discovery, risk stratification, therapeutic target identification, and personalized treatment strategies. OncoProExp is freely accessible at https://oncopro.cs.ut.ee/ without login requirements, offering a comprehensive resource for translational cancer research.

bioinformatics↗

PL1 Peptide Engages Acidic Surfaces on Tumor-Associated Fibronectin and Tenascin Isoforms to Trigger Cellular Uptake.

Tumor extracellular matrix (ECM) is a high-capacity and genetically stable target for the precision delivery of affinity ligand-guided drugs and imaging agents. Recently, we developed a PL1 peptide (sequence: PPRRGLIKLKTS) for systemic targeting of malignant ECM. Here we map the dynamics of PL1 binding to its receptors Fibronectin Extra Domain B (FN-EDB) and Tenascin C C-isoform (TNC-C) by computational modeling and cell-free binding studies on mutated receptor proteins, and study cellular binding and internalization of PL1 nanoparticles in cultured cells. Molecular dynamics simulation and docking analysis suggested that the engagement of PL1 peptide with both receptors is primarily driven by electrostatic interactions. Substituting acidic amino acid residues with neutral amino acids at predicted PL1 binding sites in FN-EDB (D52N-D49N-D12N) and TNC-C (D39N-D45N) resulted in the loss of binding of PL1 nanoparticles. Remarkably, PL1-functionalized nanoparticles (NPs) were not only deposited on the target ECM but bound the cells and initiated a robust cellular uptake via a pathway resembling macropinocytosis. Our studies establish the mode of engagement of the PL1 peptide with its receptors and suggest applications for intracellular delivery of nanoscale payloads. The outcomes of this work can be used for the development of PL1-derived peptides with improved stability, affinity and specificity for precision targeting of the tumor ECM and malignant cells. One Sentence SummaryPL1 peptide is recruited to the acidic surfaces on oncofetal fibronectin EDB and tenascin C-C isoform, triggering cellular uptake of PL1-functionalized nanoparticles.

cancer biology↗