Insights into Proteomic Immune Cell Signaling and Communication via Data-Driven Modeling

Author(s):  
Kelly F. Benedict ◽  
Douglas A. Lauffenburger
Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2632
Author(s):  
Aparajita Budithi ◽  
Sumeyye Su ◽  
Arkadz Kirshtein ◽  
Leili Shahriyari

Many colon cancer patients show resistance to their treatments. Therefore, it is important to consider unique characteristic of each tumor to find the best treatment options for each patient. In this study, we develop a data driven mathematical model for interaction between the tumor microenvironment and FOLFIRI drug agents in colon cancer. Patients are divided into five distinct clusters based on their estimated immune cell fractions obtained from their primary tumors’ gene expression data. We then analyze the effects of drugs on cancer cells and immune cells in each group, and we observe different responses to the FOLFIRI drugs between patients in different immune groups. For instance, patients in cluster 3 with the highest T-reg/T-helper ratio respond better to the FOLFIRI treatment, while patients in cluster 2 with the lowest T-reg/T-helper ratio resist the treatment. Moreover, we use ROC curve to validate the model using the tumor status of the patients at their follow up, and the model predicts well for the earlier follow up days.


Author(s):  
Hannah Lu ◽  
Cortney Weintz ◽  
Joseph Pace ◽  
Dhiraj Indana ◽  
Kevin Linka ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Feng Wang ◽  
Bryant Chau ◽  
Sean M. West ◽  
Christopher R. Kimberlin ◽  
Fei Cao ◽  
...  

AbstractGlucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) are members of the tumor necrosis superfamily that play a role in immune cell signaling, activation, and survival. GITR is a therapeutic target for directly activating effector CD4 and CD8 T cells, or depleting GITR-expressing regulatory T cells (Tregs), thereby promoting anti-tumor immune responses. GITR activation through its native ligand is important for understanding immune signaling, but GITR structure has not been reported. Here we present structures of human and mouse GITR receptors bound to their cognate ligands. Both species share a receptor–ligand interface and receptor–receptor interface; the unique C-terminal receptor–receptor enables higher order structures on the membrane. Human GITR–GITRL has potential to form a hexameric network of membrane complexes, while murine GITR–GITRL complex forms a linear chain due to dimeric interactions. Mutations at the receptor–receptor interface in human GITR reduce cell signaling with in vitro ligand binding assays and minimize higher order membrane structures when bound by fluorescently labeled ligand in cell imaging experiments.


Mathematics ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 949
Author(s):  
Keita Hara ◽  
Masaki Inoue

In this paper, we address the data-driven modeling of a nonlinear dynamical system while incorporating a priori information. The nonlinear system is described using the Koopman operator, which is a linear operator defined on a lifted infinite-dimensional state-space. Assuming that the L2 gain of the system is known, the data-driven finite-dimensional approximation of the operator while preserving information about the gain, namely L2 gain-preserving data-driven modeling, is formulated. Then, its computationally efficient solution method is presented. An application of the modeling method to feedback controller design is also presented. Aiming for robust stabilization using data-driven control under a poor training dataset, we address the following two modeling problems: (1) Forward modeling: the data-driven modeling is applied to the operating data of a plant system to derive the plant model; (2) Backward modeling: L2 gain-preserving data-driven modeling is applied to the same data to derive an inverse model of the plant system. Then, a feedback controller composed of the plant and inverse models is created based on internal model control, and it robustly stabilizes the plant system. A design demonstration of the data-driven controller is provided using a numerical experiment.


Author(s):  
Shams Kalam ◽  
Rizwan Ahmed Khan ◽  
Shahnawaz Khan ◽  
Muhammad Faizan ◽  
Muhammad Amin ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document