In cancer research, understanding the interplay between specific genetic mutations and pathway activations is crucial for uncovering disease mechanisms and developing targeted therapies. Combination searches allow researchers to identify cell lines that exhibit multiple molecular features, such as mutations in key genes (e.g., BRCA1/2) and activation of critical signaling pathways (e.g., WNT). These insights can reveal potential biomarkers, therapeutic targets, and resistance mechanisms.
This is the second article in a series that demonstrates how to perform combination searches in Meritudio’s Tumor Models Database. In this guide, we will focus on identifying cell lines with:
● BRCA mutations (BRCA1 and/or BRCA2 mutations), which are commonly associated with DNA repair deficiencies and cancer susceptibility.
● WNT pathway activation, a key signaling pathway involved in cell proliferation, differentiation, and cancer progression.
The animated graph shows the operations to identify 16 cell lines satisfying the search criteria:
● The combination search is accomplished by the use of logic operators OR and AND.
● The three filters form the search criteria: ((BRCA1: & mutation = Somatic) OR (BRCA2: & mutation = Somatic)) AND (KEGG_WNT_SIGNALING_PATHWAY: MetaScore = 1.5~2.8), which means (BRCA1_mutation OR BRCA2_mutation) AND WNT_pathway_activation.
● There are several WNT pathways, we used KEGG_WNT_SIGNALING_PATHWAY in the search, but others can be used as well, such as HALLMARK_WNT_BETA_CATENIN_SIGNALING, BIOCARTA_WNT_PATHWAY, REACTOME_SIGNALING_BY_WNT, WP_WNT_SIGNALING_PATHWAY.
