Stabilized COre gene and Pathway Election uncovers pan-cancer shared pathways and a cancer-specific driver.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36542714.
- Also identified by DOI 10.1126/sciadv.abo2846 and PMC identifier 9770999.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Approaches systematically characterizing interactions via transcriptomic data usually follow two systems: (i) coexpression network analyses focusing on correlations between genes and (ii) linear regressions (usually regularized) to select multiple genes jointly. Both suffer from the problem of stability: A slight change of parameterization or dataset could lead to marked alterations of outcomes. Here, we propose Stabilized COre gene and Pathway Election (SCOPE), a tool integrating bootstrapped least absolute shrinkage and selection operator and coexpression analysis, leading to robust outcomes insensitive to variations in data. By applying SCOPE to six cancer expression datasets (BRCA, COAD, KIRC, LUAD, PRAD, and THCA) in The Cancer Genome Atlas, we identified core genes capturing interaction effects in crucial pan-cancer pathways related to genome instability and DNA damage response. Moreover, we highlighted the pivotal role of <i>CD63</i> as an oncogenic driver and a potential therapeutic target in kidney cancer. SCOPE enables stabilized investigations toward complex interactions using transcriptome data.