ArticleOncotarget2014
Quantitative network mapping of the human kinome interactome reveals new clues for rational kinase inhibitor discovery and individualized cancer therapy.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 116 citations in OpenAlex.
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- A Network-Driven Framework for Drug Response Precision Prediction of Acute Myeloid Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Identification of Parkinson's disease PACE subtypes and repurposing treatments through integrative analyses of multimodal data.NPJ digital medicine · 2024Article
- Bifunctional Inhibitor Reveals NEK2 as a Therapeutic Target and Regulator of Oncogenic Pathways in Lymphoma.Molecular cancer therapeutics · 2024Article
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- Interpretable deep learning translation of GWAS and multi-omics findings to identify pathobiology and drug repurposing in Alzheimer's disease.Cell reports · 2022Article
- NESM: a network embedding method for tumor stratification by integrating multi-omics data.G3 (Bethesda, Md.) · 2022Article
- Single-cell network biology characterizes cell type gene regulation for drug repurposing and phenotype prediction in Alzheimer's disease.PLoS computational biology · 2022Article
- A comprehensive SARS-CoV-2-human protein-protein interactome network identifies pathobiology and host-targeting therapies for COVID-19.Research square · 2022Article
- Molecular Mechanisms, Biomarkers and Emerging Therapies for Chemotherapy Resistant TNBC.International journal of molecular sciences · 2022Review
- Identifying Candidate Flavonoids for Non-Alcoholic Fatty Liver Disease by Network-Based Strategy.Frontiers in pharmacology · 2022Article
- Identification of transcriptional regulatory network associated with response of host epithelial cells to SARS-CoV-2.Scientific reports · 2021Article
- Network-based modeling of herb combinations in traditional Chinese medicine.Briefings in bioinformatics · 2021Article
- KEA3: improved kinase enrichment analysis via data integration.Nucleic acids research · 2021Article
- Constraint-based models for dominating protein interaction networks.IET systems biology · 2021Article
- Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment.Alzheimer's research & therapy · 2021Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The human kinome is gaining importance through its promising cancer therapeutic targets, yet no general model to address the kinase inhibitor resistance has emerged. Here, we constructed a systems biology-based framework to catalogue the human kinome, including 538 kinase genes, in the broader context of the human interactome. Specifically, we constructed three networks: a kinase-substrate interaction network containing 7,346 pairs connecting 379 kinases to 36,576 phosphorylation sites in 1,961 substrates, a protein-protein interaction network (PPIN) containing 92,699 pairs, and an atomic resolution PPIN containing 4,278 pairs. We identified the conserved regulatory phosphorylation motifs (e.g., Ser/Thr-Pro) using a sequence logo analysis. We found the typical anticancer target selection strategy that uses network hubs as drug targets, might lead to a high adverse drug reaction risk. Furthermore, we found the distinct network centrality of kinases creates a high anticancer drug resistance risk by feedback or crosstalk mechanisms within cellular networks. This notion is supported by the systematic network and pathway analyses that anticancer drug resistance genes are significantly enriched as hubs and heavily participate in multiple signaling pathways. Collectively, this comprehensive human kinome interactome map sheds light on anticancer drug resistance mechanisms and provides an innovative resource for rational kinase inhibitor design.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.