Maldonado Pablo, Dutt Taru S, Hitpas Amanda, Podell Brendan, Anderson G Brooke, Henao-Tamayo Marcela
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA.
Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO, USA.
NPJ Syst Biol Appl. 2025 Aug 10;11(1):90. doi: 10.1038/s41540-025-00572-4.
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills ~1.3 million people annually. Accordingly, vaccines and sophisticated analytical tools are necessary to evaluate their effectiveness. To address these challenges, we created a Generalized Linear Model (GLM) framework to evaluate high-dimensional flow cytometry data and the multivariable influences on immune responses, accommodating proportional and non-normal data, and violations of assumptions set by classical statistical evaluations. In naïve mice vaccinated with BCG boosted with ID93-GLA-SE, we used GLMs to assess the impact of sex, vaccination, and days post-infection on probabilities of immune cell phenotypes following Mtb challenge. We demonstrate enhanced T cell responses in the lung following BCG + ID93-GLA-SE compared to BCG or ID93-GLA-SE alone, with notable sex differences in humoral immunity. This framework highlights GLMs in assessing complex datasets while enhancing our comprehension of independent continuous and categorical variables on vaccine efficacy, and serves as a foundation for deeper, more complex scenarios.
由结核分枝杆菌（Mtb）引起的结核病（TB）每年导致约130万人死亡。因此，疫苗和先进的分析工具对于评估其有效性是必要的。为应对这些挑战，我们创建了一个广义线性模型（GLM）框架，以评估高维流式细胞术数据以及对免疫反应的多变量影响，该框架适用于比例数据和非正态数据，并能处理经典统计评估所设定假设的违反情况。在用ID93-GLA-SE加强免疫的卡介苗接种的未感染小鼠中，我们使用GLM来评估性别、疫苗接种和感染后天数对结核分枝杆菌攻击后免疫细胞表型概率的影响。我们证明，与单独使用卡介苗或ID93-GLA-SE相比，卡介苗+ID93-GLA-SE接种后肺部T细胞反应增强，体液免疫存在显著的性别差异。该框架突出了GLM在评估复杂数据集方面的作用，同时增强了我们对疫苗效力中独立连续变量和分类变量的理解，并为更深入、更复杂的情况奠定了基础。
