NetSDR: Drug repurposing for cancers based on subtype-specific network modularization and perturbation analysis

IF 4.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bin Yang , Wanshi Li , Zhen Xu , Wei Li , Guang Hu
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引用次数: 0

Abstract

Cancer, a heterogeneous disease, presents significant challenges for drug development due to its complex etiology. Drug repurposing, particularly through network medicine approaches, offers a promising avenue for cancer treatment by analyzing how drugs influence cellular networks on a systemic scale. The advent of large-scale proteomics data provides new opportunities to elucidate regulatory mechanisms specific to cancer subtypes. Herein, we present NetSDR, a Network-based Subtype-specific Drug Repurposing framework for prioritizing repurposed drugs specific to certain cancer subtypes, guided by subtype-specific proteomic signatures and network perturbations. First, by integrating cancer subtype information into a network-based method, we developed a pipeline to recognize subtype-specific functional modules. Next, we conducted drug response analysis for each module to identify the “therapeutic module” and then used deep learning to construct weighted drug response network for the particular subtype. Finally, we employed a perturbation response scanning-based drug repurposing method, which incorporates dynamic information, to facilitate the prioritization of candidate drugs. Applying the framework to gastric cancer, we attested the significance of the extracellular matrix module in treatment strategies and discovered a promising potential drug target, LAMB2, as well as a series of possible repurposed drugs. This study demonstrates a systems biology framework for precise drug repurposing in cancer and other complex diseases.
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来源期刊
CiteScore
12.30
自引率
0.00%
发文量
218
审稿时长
32 days
期刊介绍: BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.
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