Sivanathan Suruthy, Hu Ting
School of Computing and the Department of Biomedical and Molecular Sciences, Queen's University, Goodwin Hall, Kingston, K7L 2N8, Ontario, Canada.
School of Computing, Queen's University, Goodwin Hall, Kingston, K7L 2 N8, Ontario, Canada.
BioData Min. 2025 May 2;18(1):32. doi: 10.1186/s13040-025-00444-x.
Acute myeloid leukemia (AML) is caused by proliferation of mutated myeloid progenitor cells. The standard chemotherapy regimen does not efficiently cause remission as there is a high relapse rate. Resistance acquired by leukemic stem cells is suggested to be one of the root causes of relapse. Therefore, there is an urgency to develop new drugs for therapy. Repurposing approved drugs for AML can provide a cost-friendly, time-efficient, and affordable alternative. The multiscale interactome network is a computational tool that can identify potential therapeutic candidates by comparing mechanisms of the drug and disease. Communities that could be potentially experimentally validated are detected in the multiscale interactome network using the algorithm CRank. The results are evaluated through literature search and Gene Ontology (GO) enrichment analysis. In this research, we identify therapeutic candidates for AML and their mechanisms from the interactome, and isolate prioritized communities that are dominant in the therapeutic mechanism that could potentially be used as a prompt for pre-clinical/translational research (e.g. bioinformatics, laboratory research) to focus on biological functions and mechanisms that are associated with the disease and drug. This method may allow for an efficient and accelerated discovery of potential candidates for AML, a rapidly progressing disease.
急性髓系白血病（AML）是由突变的髓系祖细胞增殖引起的。由于复发率高，标准化疗方案不能有效地导致缓解。白血病干细胞获得的耐药性被认为是复发的根本原因之一。因此，迫切需要开发新的治疗药物。将已批准的药物重新用于治疗AML可以提供一种成本友好、省时且经济实惠的替代方案。多尺度相互作用组网络是一种计算工具，它可以通过比较药物和疾病的机制来识别潜在的治疗候选物。使用CRank算法在多尺度相互作用组网络中检测可能通过实验验证的群落。通过文献检索和基因本体（GO）富集分析对结果进行评估。在本研究中，我们从相互作用组中识别AML的治疗候选物及其机制，并分离出在治疗机制中占主导地位的优先群落，这些群落可能被用作临床前/转化研究（如生物信息学、实验室研究）的提示，以关注与疾病和药物相关的生物学功能和机制。这种方法可能有助于高效、加速地发现AML潜在候选物，AML是一种进展迅速的疾病。
