Biology subjects

Kondratova, M.

Publications and source records attributed to Kondratova, M..

3 recordsLinked to original sources

bioRxiv2024

A coregulatory influence map of glioblastoma heterogeneity and plasticity - From cells in vitro to tumors and back again

We present GBM-cRegMap, an online resource providing a comprehensive coregulatory influence network perspective on glioblastoma (GBM) heterogeneity and plasticity. Using representation learning algorithms, we derived two components of this resource: GBM-CoRegNet, a highly specific coregulatory network of tumor cells, and GBM-CoRegMap, a unified network influence map based on 1612 tumors from 16 studies. As a widely applicable closed-loop system connecting cellular models and tumors, GBM-cRegMap will provide the GBM research community with an easy-to-use web tool (https://gbm.cregmap.com) that maps any existing or newly generated transcriptomic "query" data to a reference coregulatory network and a large-scale manifold of disease heterogeneity. Using GBM-cRegMap, we demonstrated the synergy between the two components by refining the molecular classification of GBM, identifying potential key regulators, and aligning the transcriptional profiles of tumors and in vitro models. Through the amalgamation of a vast dataset, we validated the proneural (PN)-mesenchymal (MES) axis and identified three subclasses of classical (CL) tumors: astrocyte-like (CL-A), epithelial basal-like (CL-B), and cilium-rich (CL-C). We revealed the CL-C subclass, an intermediate state demonstrating the plasticity of GBM cells along the PN-MES axis under chemotherapy. We identified key regulators, such as PAX8, and NKX2.5, involved in TMZ resistance. Notably, NKX2.5, more expressed in higher-grade gliomas, negatively impacts patient survival and regulates genes involved in glucose metabolism. O_FIG O_LINKSMALLFIG WIDTH=152 HEIGHT=200 SRC="FIGDIR/small/609303v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@c7a401org.highwire.dtl.DTLVardef@e0681corg.highwire.dtl.DTLVardef@d31f55org.highwire.dtl.DTLVardef@ae350f_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2017

Application of Atlas of Cancer Signalling Network in pre-clinical studies

Initiation and progression of cancer involve multiple molecular mechanisms. The knowledge on these mechanisms is expanding and should be converted into guidelines for tackling the disease. We discuss here formalization of biological knowledge into a comprehensive resource Atlas of Cancer Signalling Network (ACSN) and Google Maps-based tool NaviCell that supports map navigation. The application of maps for omics data visualisation in the context of signalling maps is possible using NaviCell Web Service module and NaviCom tool for generation of network-based molecular portraits of cancer using multi-level omics data. We review how these resources and tools are applied for cancer pre-clinical studies among others for rationalizing synergistic effect of drugs and designing complex disease stage-specific druggable interventions following structural analysis of the maps together with omics data. Modules and maps of ACSN as signatures of biological functions, can help in cancer data analysis and interpretation. In addition, they can also be used to find association between perturbations in particular molecular mechanisms to the risk of a specific cancer type development. These approaches and beyond help to study interplay between molecular mechanisms of cancer, deciphering how gene interactions govern hallmarks of cancer in specific context. We discuss a perspective to develop a flexible methodology and a pipeline to enable systematic omics data analysis in the context of signalling network maps, for stratifying patients and suggesting interventions points and drug repositioning in cancer and other human diseases.

systems biology↗

bioRxiv2016

Knowledge Formalization and High-Throughput Data Visualization Using Signaling Network Maps

Generation and usage of high-quality molecular signalling network maps can be augmented by standardising notations, establishing curation workflows and application of computational biology methods to exploit the knowledge contained in the maps. In this manuscript, we summarize the major aims and challenges of assembling information in the form of comprehensive maps of molecular interactions. Mainly, we share our experience gained while creating the Atlas of Cancer Signalling Network. In the step-by-step procedure, we describe the map construction process and suggest solutions for map complexity management by introducing a hierarchical modular map structure. In addition, we describe the NaviCell platform, a computational technology using Google Maps API to explore comprehensive molecular maps similar to geographical maps, and explain the advantages of semantic zooming principles for map navigation. We also provide the outline to prepare signalling network maps for navigation using the NaviCell platform. Finally, several examples of cancer high-throughput data analysis and visualization in the context of comprehensive signalling maps are presented.

systems biology↗