Protein-driven inference of miRNA-disease associations

TY - JOUR

T1 - Protein-driven inference of miRNA-disease associations

AU - Mørk, Søren

AU - Pletscher-Frankild, Sune

AU - Palleja, Albert

AU - Gorodkin, Jan

AU - Jensen, Lars Juhl

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Motivation: MicroRNAs (miRNAs) are a highly abundant class of noncoding RNA genes involved in cellular regulation and thus also diseases. Despite miRNAs being important disease factors, miRNA-disease associations remain low in number and of variable reliability. Furthermore, existing databases and prediction methods do not explicitly facilitate forming hypotheses about the possible molecular causes of the association, thereby making the path to experimental follow-up longer. Results: Here we present miRPD in which miRNA-Protein-Disease associations are explicitly inferred. Besides linking miRNAs to diseases, it directly suggests the underlying proteins involved, which can be used to form hypotheses that can be experimentally tested. The inference of miRNAs and diseases is made by coupling known and predicted miRNA-protein associations with protein-disease associations text mined from the literature. We present scoring schemes that allow us to rank miRNA-disease associations inferred from both curated and predicted miRNA targets by reliability and thereby to create high- and medium-confidence sets of associations. Analyzing these, we find statistically significant enrichment for proteins involved in pathways related to cancer and type I diabetes mellitus, suggesting either a literature bias or a genuine biological trend. We show by example how the associations can be used to extract proteins for disease hypothesis.

AB - Motivation: MicroRNAs (miRNAs) are a highly abundant class of noncoding RNA genes involved in cellular regulation and thus also diseases. Despite miRNAs being important disease factors, miRNA-disease associations remain low in number and of variable reliability. Furthermore, existing databases and prediction methods do not explicitly facilitate forming hypotheses about the possible molecular causes of the association, thereby making the path to experimental follow-up longer. Results: Here we present miRPD in which miRNA-Protein-Disease associations are explicitly inferred. Besides linking miRNAs to diseases, it directly suggests the underlying proteins involved, which can be used to form hypotheses that can be experimentally tested. The inference of miRNAs and diseases is made by coupling known and predicted miRNA-protein associations with protein-disease associations text mined from the literature. We present scoring schemes that allow us to rank miRNA-disease associations inferred from both curated and predicted miRNA targets by reliability and thereby to create high- and medium-confidence sets of associations. Analyzing these, we find statistically significant enrichment for proteins involved in pathways related to cancer and type I diabetes mellitus, suggesting either a literature bias or a genuine biological trend. We show by example how the associations can be used to extract proteins for disease hypothesis.

U2 - 10.1093/bioinformatics/btt677

DO - 10.1093/bioinformatics/btt677

M3 - Journal article

C2 - 24273243

SN - 1367-4803

VL - 30

SP - 392

EP - 397

JO - Bioinformatics

JF - Bioinformatics

IS - 3

ER -