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.
Contact markus.daniel.hoffmann{at}tum.de; markus.list{at}tum.de
Supplementary information Supplementary data are available at Bioinformatics online.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵* The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors
We enhanced the script with many additional analyses to give the user trust in the spongEffects method.