Bipartite network models to design combination therapies in acute myeloid leukaemia.
Mohieddin JafariMehdi MirzaieJie BaoFarnaz BarnehShuyu ZhengJohanna ErikssonCaroline A HeckmanJing TangPublished in: Nature communications (2022)
Combination therapy is preferred over single-targeted monotherapies for cancer treatment due to its efficiency and safety. However, identifying effective drug combinations costs time and resources. We propose a method for identifying potential drug combinations by bipartite network modelling of patient-related drug response data, specifically the Beat AML dataset. The median of cell viability is used as a drug potency measurement to reconstruct a weighted bipartite network, model drug-biological sample interactions, and find the clusters of nodes inside two projected networks. Then, the clustering results are leveraged to discover effective multi-targeted drug combinations, which are also supported by more evidence using GDSC and ALMANAC databases. The potency and synergy levels of selective drug combinations are corroborated against monotherapy in three cell lines for acute myeloid leukaemia in vitro. In this study, we introduce a nominal data mining approach to improving acute myeloid leukaemia treatment through combinatorial therapy.
Keyphrases
- combination therapy
- drug induced
- liver failure
- acute myeloid leukemia
- adverse drug
- respiratory failure
- squamous cell carcinoma
- dendritic cells
- magnetic resonance
- randomized controlled trial
- emergency department
- big data
- cancer therapy
- stem cells
- mesenchymal stem cells
- intensive care unit
- computed tomography
- machine learning
- heart rate
- acute lymphoblastic leukemia
- single cell
- radiation therapy
- artificial intelligence
- risk assessment
- smoking cessation
- study protocol