Functional stratification of cancer drugs through integrated network similarity

Beyge, Seyma Unsal
Tunçbağ, Nurcan
Drugs not only perturb their immediate protein targets but also modulate multiple signaling pathways. In this study, we explored networks modulated by several drugs across multiple cancer cell lines by integrating their targets with transcriptomic and phosphoproteomic data. As a result, we obtained 236 reconstructed networks covering five cell lines and 70 drugs. A rigorous topological and pathway analysis showed that chemically and functionally different drugs may modulate overlapping networks. Additionally, we revealed a set of tumor-specific hidden pathways with the help of drug network models that are not detectable from the initial data. The difference in the target selectivity of the drugs leads to disjoint networks despite sharing a similar mechanism of action, e.g., HDAC inhibitors. We also used the reconstructed network models to study potential drug combinations based on the topological separation and found literature evidence for a set of drug pairs. Overall, network-level exploration of drug-modulated pathways and their deep comparison may potentially help optimize treatment strategies and suggest new drug combinations.


Structural characterization of recombinant bovine Go alpha by spectroscopy and homology modeling
MEGA TİBER, PINAR; Orun, Oya; Nacar, Cevdet; Sezerman, Ugur Osman; Severcan, Feride; Severcan, Mete; Matagne, Andre; KAN, BEKİ (2011-01-01)
Go, a member of heterotrimeric guanine nucleotide-binding proteins, is the most abundant form of G protein in the central and peripheral nervous systems. Go alpha has a significant role in neuronal development and function but its signal transduction mechanism remains to be clarified.
Protein-Protein Interactions in Live Cells: Reinventing the Wheel
Son, Çağdaş Devrim (2018-12-13)
G protein-coupled receptors (GPCRs) are membrane proteins that mediate physiologicalresponse to a diverse array of stimuli. In humans, they mediate the action of hundreds ofpeptide hormones, sensory stimuli, odorants, neurotransmitters, and chemokines. GPCRs alsoare targets for ~40% of all currently marketed pharmaceuticals. These receptors traditionallybeen thought to act as monomeric units. However, recent evidence suggests that GPCRs mayform dimers as part of their normal trafficking and function. While ...
Metabolic engineering of aromatic group amino acid pathway in Bacillus subtilis for L-phenylalanine production
Ozcelik, IS; Çalık, Pınar; Calik, G; Ozdamar, TH (Elsevier BV, 2004-11-01)
Metabolic control sites in the aromatic group amino acid pathway (AAAP) of Bacillus subtilis for L-Phenylalanine (Phe) overproduction were determined; and aiming pathway flux amplification, by cloning the flux controlling gene aroH to a multi-copy plasmid, the impact of single gene cloning on pathway flux distributions were investigated. The branch-point metabolites E4P and PEP+E4P supplied in vitro, enhanced Phe production and well defined perturbations were achieved on the AAAP reactions. The intracellula...
GURSEL, I; Hasırcı, Vasıf Nejat (1992-01-01)
In this study, matrix entrapment of the enzyme glucose oxidase was achieved through gamma-irradiation of monomers N-vinyl pyrrolidone, 2-hydroxyethyl methacrylate and their mixture. To test the effect of radiation on entrapment efficiency, retention of activities and properties of the system, duration and temperature were varied. The reusability of the resultant products was tested. It was generally found that inclusion of the hydrophilic monomer N-vinyl pyrrolidone into the matrix increased the water conte...
Interactions between G-protein Coupled Receptors and Ligand Gated Ion Channels (GPCR-LGIC COUPLING)
Son, Çağdaş Devrim(2014-9-30)
Dopamine receptors are members of G-protein coupled receptor superfamily. These receptors are the key point of dopaminergic system, which controls the regulation of memory, attention, food intake, endocrine regulation, psychomotor activity and positive reinforcement. To regulate so many critically important neurological events, dopamine receptors have complex interactions with other receptors and ion channels. In this study, a trimeric complex comprising D2 receptor -which is a subtype of dopamine receptors...
Citation Formats
S. U. Beyge and N. Tunçbağ, “Functional stratification of cancer drugs through integrated network similarity,” NPJ SYSTEMS BIOLOGY AND APPLICATIONS, vol. 8, no. 1, pp. 0–0, 2022, Accessed: 00, 2022. [Online]. Available: