Alex C Soupir, Ishaan V Gadiyar, Bryan R Helm, Coleman R Harris, Simon N Vandekar, Lauren C Peres, Robert J Coffey, Julia Wrobel, Siyuan Ma, Brooke L Fridley
{"title":"Benchmarking Spatial Co-Localization Methods for Single-Cell Multiplex Imaging Data with Applications to High-Grade Serous Ovarian and Triple Negative Breast Cancer.","authors":"Alex C Soupir, Ishaan V Gadiyar, Bryan R Helm, Coleman R Harris, Simon N Vandekar, Lauren C Peres, Robert J Coffey, Julia Wrobel, Siyuan Ma, Brooke L Fridley","doi":"10.1080/29979676.2024.2437947","DOIUrl":"10.1080/29979676.2024.2437947","url":null,"abstract":"<p><p>Single-cell multiplex imaging (scMI) measures cell locations and phenotypes within a tissue and can be used to understand the tumor microenvironment. In scMI studies, it is often of interest to quantify spatial co-localization of immune cells and its association with clinical outcomes; however, it remains unknown which of the many available spatial indices have adequate power to detect spatial within-sample co-localization and its association with patient outcomes, such as survival. In this study, the performance of six frequentist metrics of spatial co-localization used in scMI studies were evaluated. Simulated data was used to assess the power and type I error of these spatial metrics to detect signficant co-localization. Furthermore, these spatial co-localization methods were applied to two scMI studies - a high-grade serous ovarian cancer (HGSOC) study and triple negative breast cancer (TNBC) study - to detect within-sample co-localization between cell types and their sensitivity to detect differences in survival across samples. In the simulation study, Ripley's <i>K</i> had the greatest power to identify co-localization followed closely by pair correlation <i>g</i>; all other statistics showed little power across all simulation scenarios. In the application of the methods to cancer studies, the results consistently point to pair correlation <i>g</i> and Ripley's <i>K</i> as indices with the most power for detecting significant co-localization in scMI data. Furthermore, pair correlation <i>g</i>, Ripley's <i>K</i>, and the scLMM index were most effective for estimating between-sample associations between level of co-localization and survival.</p>","PeriodicalId":520439,"journal":{"name":"Statistics and data science in imaging","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}