Ülkü Ünsal, Ali Cüvitoğlu, Kemal Turhan, Zerrin Işik
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NMSDR: Drug repurposing approach based on transcriptome data and network module similarity.
Computational drug repurposing aims to discover new treatment regimens by analyzing approved drugs on the market. This study proposes previously approved compounds that can change the expression profile of disease-causing proteins by developing a network theory-based drug repurposing approach. The novelty of the proposed approach is an exploration of module similarity between a disease-causing network and a compound-specific interaction network; thus, such an association leads to more realistic modeling of molecular cell responses at a system biology level. The overlap of the disease network and each compound-specific network is calculated based on a shortest-path similarity of networks by accounting for all protein pairs between networks. A higher similarity score indicates a significant potential of a compound. The approach was validated for breast and lung cancers. When all compounds are sorted by their normalized-similarity scores, 36 and 16 drugs are proposed as new candidates for breast and lung cancer treatment, respectively. A literature survey on candidate compounds revealed that some of our predictions have been clinically investigated in phase II/III trials for the treatment of two cancer types. As a summary, the proposed approach has provided promising initial results by modeling biochemical cell responses in a network-level data representation.
期刊介绍:
Molecular Informatics is a peer-reviewed, international forum for publication of high-quality, interdisciplinary research on all molecular aspects of bio/cheminformatics and computer-assisted molecular design. Molecular Informatics succeeded QSAR & Combinatorial Science in 2010.
Molecular Informatics presents methodological innovations that will lead to a deeper understanding of ligand-receptor interactions, macromolecular complexes, molecular networks, design concepts and processes that demonstrate how ideas and design concepts lead to molecules with a desired structure or function, preferably including experimental validation.
The journal''s scope includes but is not limited to the fields of drug discovery and chemical biology, protein and nucleic acid engineering and design, the design of nanomolecular structures, strategies for modeling of macromolecular assemblies, molecular networks and systems, pharmaco- and chemogenomics, computer-assisted screening strategies, as well as novel technologies for the de novo design of biologically active molecules. As a unique feature Molecular Informatics publishes so-called "Methods Corner" review-type articles which feature important technological concepts and advances within the scope of the journal.