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spongEffects: ceRNA modules offer patient-specific insights into the miRNA regulatory landscape

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Motivation Cancer is one of the leading causes of death worldwide. Despite significant improvements in prevention and treatment, mortality remains high for many cancer types. Hence, innovative methods that use… Click to show full abstract

Motivation Cancer is one of the leading causes of death worldwide. Despite significant improvements in prevention and treatment, mortality remains high for many cancer types. Hence, innovative methods that use molecular data to stratify patients and identify biomarkers are needed. Promising biomarkers can also be inferred from competing endogenous RNA (ceRNA) networks that capture the gene-miRNA gene regulatory landscape. Thus far, the role of these biomarkers could only be studied globally but not in a sample-specific manner. To mitigate this, we introduce spongEffects, a novel method that infers subnetworks (or modules) from ceRNA networks and calculates patient- or sample-specific scores related to their regulatory activity. Results We show how spongEffects can be used for downstream interpretation and machine learning tasks such as tumor classification and for identifying subtype-specific regulatory interactions. In a concrete example of breast cancer subtype classification, we prioritize modules impacting the biology of the different subtypes. In summary, spongEffects prioritizes ceRNA modules as biomarkers and offers insights into the miRNA regulatory landscape. Notably, these module scores can be inferred from gene expression data alone and can thus be applied to cohorts where miRNA expression information is lacking. Availability https://bioconductor.org/packages/devel/bioc/html/SPONGE.html Contact [email protected]; [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

Keywords: mirna regulatory; insights mirna; regulatory landscape; spongeffects cerna; cerna modules; landscape

Journal Title: Bioinformatics
Year Published: 2023

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