A novel similarity score based on gene ranks to reveal genetic relationships among diseases

Abstract

Knowledge of similarities among diseases can contribute to uncovering common genetic mechanisms. Based on ranked gene lists, a couple of similarity measures were proposed in the literature. Notice that they may suffer from the determination of cutoff or heavy computational load, we propose a novel similarity score SimSIP among diseases based on gene ranks. Simulation studies under various scenarios demonstrate that SimSIP has better performance than existing rank-based similarity measures. Application of SimSIP in gene expression data of 18 cancer types from The Cancer Genome Atlas shows that SimSIP is superior in clarifying the genetic relationships among diseases and demonstrates the tendency to cluster the histologically or anatomically related cancers together, which is analogous to the pan-cancer studies. Moreover, SimSIP with simpler form and faster computation is more robust for higher levels of noise than existing methods and provides a basis for future studies on genetic relationships among diseases. In addition, a measure MAG is developed to gauge the magnitude of association of anindividual gene with diseases. By using MAG the genes and biological processes significantly associated with colorectal cancer are detected.

Transcriptional activation of Jun and Fos members of the AP‐1 complex is a conserved signature of immune aging that contributes to inflammaging

“…To uncover the most conserved signatures of immune aging, we first compared age‐related gene expression changes between the two strains within each tissue, which revealed a positive and significant correlation suggesting that most age‐related changes are conserved (correlation coefficient R = 0.44 to 0.61, p < 2.2.e−16 for all tissues) (Figure 2a ). To uncover genes that are the most significantly and robustly associated with aging, we calculated a novel similarity score based on the magnitude of association of genes (MAG) to a phenotype, which was originally developed to assess the similarity between diseases (Luo et al, 2021 ). First, we calculated MAG scores for each gene based on their association with aging across the 4 studied cells/tissues as well as the two strains (Figure 2b , Table S5 ).…”

“…To uncover genes that are the most significantly and robustly associated with aging, we calculated a similarity score based on the magnitude of association of genes (MAG (Luo et al, 2021 )) to a phenotype. The MAG score was calculated by computing the geometric mean of the inverse of ranks of a gene for the two strains.…”

“…To uncover genes that are the most significantly and robustly associated with aging, we calculated a novel similarity score based on the magnitude of association of genes (MAG) to a phenotype, which was originally developed to assess the similarity between diseases (Luo et al, 2021). First, we calculated MAG scores for each gene based on their association with aging across the 4 studied cells/tissues as well as the two strains (Figure 2b, Table S5).…”

Transcriptional activation of Jun and Fos members of the AP-1 complex is a conserved signature of immune aging that contributes to inflammaging

“…To uncover the most conserved signatures of immune aging, we first compared age-related gene expression changes between the two strains within each tissue, which revealed a positive and significant correlation suggesting that most age-related changes are conserved (correlation coefficient R=0.44 to 0.61, p < 2.2.e-16 for all tissues) ( Figure 2A ). To uncover genes that are the most significantly and robustly associated with aging, we calculated a novel similarity score based on the magnitude of association of genes (MAG) to a phenotype, which was originally developed to assess the similarity between diseases (24) . First, we calculated MAG scores for each gene based on their association with aging across the 4 studied cells/tissues as well as the two strains ( Figure 2B, Table S5 ).…”

“…To uncover genes that are the most significantly and robustly associated with aging, we calculated a similarity score based on the magnitude of association of genes (MAG (24) ) to a phenotype. The MAG score was calculated by computing the geometric mean of the inverse of ranks of a gene for the 2 strains.…”