Journal: Computational and Structural Biotechnology Journal
Article Title: QeITH: Quantifies Tumor Ecosystem Heterogeneity to Predict Cancer Progression and Treatment Benefit
doi: 10.34133/csbj.0061
Figure Lengend Snippet: Robustness and benchmarking of QeITH. (A) Evaluation of QeITH performance in distinguishing immunotherapy responders from nonresponders using matched SKCM bulk and single-cell data. Left: Scatterplot showing strong Spearman correlation between ITH scores derived from bulk RNA-seq and cell composition-based ITH scores from single-cell data. Right: Boxplots with jittered points showing QeITH and DEPTH2 scores in responders versus nonresponders. (B) Pan-cancer comparison of QeITH and DEPTH2 scores between tumor and normal tissues in pseudobulk samples derived from scRNA-seq data. ITH scores were significantly elevated in tumors compared to normal tissues in pan-cancer analysis and validated in lung, pancreatic, and gastric cancers individually. DEPTH2 failed to detect significant tumor-normal differences in pan-cancer, pancreatic, or gastric cancer, and unexpectedly showed higher scores in normal lung tissues compared to tumors. Dot plots show individual sample values; each dot represents one sample. White diamonds indicate median values for each group. For the remaining panels, half-violins (right side) show density distributions; boxplots with overlaid line segments show median, IQR, and individual sample values (each line segment represents a single sample). (C) Stability of QeITH and ROGUE across clustering resolutions in SKCM single-cell data. Heatmaps showing Spearman rank correlations of sample rankings between resolution pairs. QeITH demonstrated high stability across resolutions, while ROGUE-based heterogeneity scores showed substantially lower consistency. (D) Comparison of QeITH and ROGUE in 2 independent single-cell datasets. Boxplots with jittered points show median, IQR, and individual sample values. Left: Kidney cancer dataset (Young et al.). QeITH detected significant differences between tumor and normal tissues, while ROGUE showed no significant difference. Right: Lung cancer dataset (Maynard et al.). QeITH showed trends approaching significance for smoker versus nonsmoker and responder versus nonresponder, while ROGUE showed no significant differences. The 2-tailed Mann–Whitney U test P values are shown.
Article Snippet: We downloaded 12 scRNA-seq datasets from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) ( https://www.ncbi.nlm.nih.gov/geo/ ).
Techniques: Single Cell, Derivative Assay, RNA Sequencing, Comparison, MANN-WHITNEY