This study benchmarks the robustness and resilience of computational deconvolution methods for estimating cell-type proportions in bulk tissues, with a focus on comparing reference-based and reference-free methods. Robustness is evaluated by generating in silico pseudo-bulk tissue RNA sequencing data from cell-level gene expression profiles derived from four different tissue types, with simulated cellular composition at varying levels of heterogeneity. To assess resilience, we intentionally alter single-cell RNA profiles to create pseudo-bulk tissue RNA-seq data. Deconvolution estimates are compared with ground truth using Pearson's correlation coefficient, root mean squared deviation, and mean absolute deviation. The results show that reference-based methods are more robust when reliable reference data are available, whereas reference-free methods excel in scenarios lacking suitable reference data. Furthermore, variations in cell-level transcriptomic profiles and cell composition have emerged as critical factors influencing the performance of deconvolution methods. This study provides significant insights into the factors affecting bulk tissue deconvolution performance, which are essential for guiding users and advancing the development of more powerful and reliable algorithms in the future.

Artificial neural networks have recently gained significant attention in biomedical research. However, their utility in survival analysis still faces many challenges. In addition to designing models for high accuracy, it is essential to optimize models that provide biologically meaningful insights. With these considerations in mind, we developed a deep neural network model, MaskedNet, to identify genes and pathways whose expression at the time of diagnosis is associated with overall survival. MaskedNet was trained using TCGA breast cancer transcriptome and clinical data, and the model’s final output was the predicted logarithm of the hazard ratio for death. The trained model was interpreted using SHapley Additive exPlanations (SHAP), a technique grounded in robust mathematical principles that assigns importance scores to input features. Compared to traditional Cox proportional hazards regression, MaskedNet had higher accuracy, as measured by Harrell’s C-index. We also found that aggregating outputs from several model runs identified multiple genes and pathways associated with overall survival, including IFNG and PIK3CA genes , along with their related pathways. To further elucidate the role of the IFNG gene, tumors were partitioned into two groups based on low and high IFNG SHAP values, respectively. Tumors with lower IFNG SHAP values exhibited higher IFNG expression and better overall survival, which were linked to more abundant presence of M1 macrophages and activated CD4+ and CD8+ T cells in the tumor microenvironment. The association of the IFNG pathway with overall survival was validated in the trastuzumab arm of the NCCTG-N9831 trial, an independent breast cancer study.

[This corrects the article PMC11643596.].

Traffic in operator networks is time varying. Conventional network functions implemented by black-boxes should satisfy the peak traffic requirement, and hence result in low resource utilization. Thanks to the emergence of Virtual Network Function (VNF), which is realized by running networking software on Virtual Machines (VMs), the operator can dynamically scale in or scale out the VNF instances and hence save the required resources. In this paper, we introduce how the dynamic VNF scaling is implemented in practical operator Data Center Networks (DCNs). First, we analyze the traffic characteristics in our operator networks, and introduce how the VNFs are organized in a common operator DCN. Based on these backgrounds, we not only propose a traffic forecasting method, but also design two VNF placement algorithms to guide the dynamic VNF instance scaling. Through both the implementation in a real operator network and extensive real trace driven simulations, we demonstrate that our dynamic VNF instance scaling system can achieve higher service availability and save the VNF resources (e.g., CPU and memory) by up to 30 percent.