Information-Theoretic Analysis of a Model of CAR-4-1BB-Mediated NFκB Activation.
Information-Theoretic Analysis of a Model of CAR-4-1BB-Mediated NFκB Activation.
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DOI：
10.1007/s11538-023-01232-6
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发表时间：
2023-12-01
影响因子：
3.5
通讯作者：
中科院分区：
文献类型：
--
作者：
系统生物学利用计算方法来检查一系列生物过程，例如细胞信号传导、代谢组学和药理学。其中包括 CAR T 细胞的数学模型，CAR T 细胞是一种癌症治疗方式，通过基因工程免疫细胞识别并对抗癌症靶点。虽然 CAR T 细胞在对抗血液系统恶性肿瘤方面取得了成功，但在对抗其他癌症类型方面的成功却有限。因此，需要更多的研究来了解它们的作用机制并充分利用它们的潜力。在我们的工作中，我们着手将信息论应用于抗原相遇后由 CAR 启动的 NFκB 信号传导的数学模型。首先，我们估计了 CAR-4-1BB 介导的 NFκB 信号转导的通道容量。接下来，我们评估了该通路区分“低”和“高”抗原浓度水平的能力，具体取决于蛋白质浓度的变异量。最后，我们评估了 NFκB 激活反映所遇到的抗原浓度的保真度，具体取决于肿瘤群体中抗原阳性靶点的患病率。我们发现，在大多数情况下，NFκB 核浓度的倍数变化比 NFκB 的绝对响应具有更高的通道容量。此外，我们发现通过途径转导抗原信号的大多数错误都倾向于低估遇到的抗原的浓度。最后，我们发现禁用 IKKβ 失活可以提高针对抗原阴性细胞靶标的信号保真度。我们对信号转导的信息论分析可以为生物信号传导提供新颖的视角，并为细胞工程提供更明智的途径。请检查并确认相应的隶属关系是否被正确识别。这是正确的。在线版本包含补充材料，可在 10.1007/s11538-023-01232-6 获取。
Systems biology utilizes computational approaches to examine an array of biological processes, such as cell signaling, metabolomics and pharmacology. This includes mathematical modeling of CAR T cells, a modality of cancer therapy by which genetically engineered immune cells recognize and combat a cancerous target. While successful against hematologic malignancies, CAR T cells have shown limited success against other cancer types. Thus, more research is needed to understand their mechanisms of action and leverage their full potential. In our work, we set out to apply information theory on a mathematical model of NFκB signaling initiated by the CAR following antigen encounter. First, we estimated channel capacity for CAR-4-1BB-mediated NFκB signal transduction. Next, we evaluated the pathway’s ability to distinguish contrasting “low” and “high” antigen concentration levels, depending on the amount of variability in protein concentrations. Finally, we assessed the fidelity by which NFκB activation reflects the encountered antigen concentration, depending on the prevalence of antigen-positive targets in tumor population. We found that in most scenarios, fold change in the nuclear concentration of NFκB carries a higher channel capacity for the pathway than NFκB’s absolute response. Additionally, we found that most errors in transducing the antigen signal through the pathway skew towards underestimating the concentration of encountered antigen. Finally, we found that disabling IKKβ deactivation could increase signaling fidelity against targets with antigen-negative cells. Our information-theoretic analysis of signal transduction can provide novel perspectives on biological signaling, as well as enable a more informed path to cell engineering.Kindly check and confirm whether the corresponding affiliation is correctly identified.this is correct The online version contains supplementary material available at 10.1007/s11538-023-01232-6.
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影响因子：
3.7
作者：
Ross BC
通讯作者：
Ross BC
影响因子：
32.4
作者：
Adelaja A;Taylor B;Sheu KM;Liu Y;Luecke S;Hoffmann A
通讯作者：
Hoffmann A
DOI：
10.2142/biophysics.1.25
发表时间：
2005
期刊：
Biophysics (Nagoya-shi, Japan)
影响因子：
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作者：
Furusawa C;Suzuki T;Kashiwagi A;Yomo T;Kaneko K
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Kaneko K
影响因子：
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作者：
SHANNON, CE
通讯作者：
SHANNON, CE
DOI：
10.1002/jha2.338
发表时间：
2022-01
期刊：
EJHaem
影响因子：
--
作者：
Sengsayadeth, Salyka;Savani, Bipin N.;Oluwole, Olalekan;Dholaria, Bhagirathbhai
通讯作者：
Dholaria, Bhagirathbhai