ABSTRACT
Gastric cancer is one of the deadliest cancers worldwide. An accurate prognosis is essential for effective clinical assessment and treatment. Spatial patterns in the tumor microenvironment (TME) are conceptually indicative of the staging and progression of gastric cancer patients. Using spatial patterns of the TME by integrating and transforming the multiplexed immunohistochemistry (mIHC) images as Cell-Graphs, we propose a graph neural network-based approach, termed Cell-Graph Signature or CGSignature, powered by artificial intelligence, for the digital staging of TME and precise prediction of patient survival in gastric cancer. In this study, patient survival prediction is formulated as either a binary (short-term and long-term) or ternary (short-term, medium-term, and long-term) classification task. Extensive benchmarking experiments demonstrate that the CGSignature achieves outstanding model performance, with Area Under the Receiver Operating Characteristic curve of 0.960 ± 0.01, and 0.771 ± 0.024 to 0.904 ± 0.012 for the binary- and ternary-classification, respectively. Moreover, Kaplan-Meier survival analysis indicates that the "digital grade" cancer staging produced by CGSignature provides a remarkable capability in discriminating both binary and ternary classes with statistical significance (P value < 0.0001), significantly outperforming the AJCC 8th edition Tumor Node Metastasis staging system. Using Cell-Graphs extracted from mIHC images, CGSignature improves the assessment of the link between the TME spatial patterns and patient prognosis. Our study suggests the feasibility and benefits of such an artificial intelligence-powered digital staging system in diagnostic pathology and precision oncology.
ABSTRACT
Persistent homology (PH) is a method used in topological data analysis (TDA) to study qualitative features of data that persist across multiple scales. It is robust to perturbations of input data, independent of dimensions and coordinates, and provides a compact representation of the qualitative features of the input. The computation of PH is an open area with numerous important and fascinating challenges. The field of PH computation is evolving rapidly, and new algorithms and software implementations are being updated and released at a rapid pace. The purposes of our article are to (1) introduce theory and computational methods for PH to a broad range of computational scientists and (2) provide benchmarks of state-of-the-art implementations for the computation of PH. We give a friendly introduction to PH, navigate the pipeline for the computation of PH with an eye towards applications, and use a range of synthetic and real-world data sets to evaluate currently available open-source implementations for the computation of PH. Based on our benchmarking, we indicate which algorithms and implementations are best suited to different types of data sets. In an accompanying tutorial, we provide guidelines for the computation of PH. We make publicly available all scripts that we wrote for the tutorial, and we make available the processed version of the data sets used in the benchmarking. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1140/epjds/s13688-017-0109-5) contains supplementary material.
