Functional combination strategy for prioritization of human miRNA target

• Published in: Gene Vol. 533; no. 1; pp. 132 - 141
• Main Authors: Li, Jing, Zhang, Yunpeng, Wang, Yingying, Zhang, Chunlong, Wang, Qiuyu, Shi, Xinrui, Li, Chunquan, Zhang, Ruijie, Li, Xia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2014
• Subjects: Functional prioritization; Humans; MicroRNAs - metabolism; Pathways; Protein Binding; Transcription Factors - metabolism; CC; PPIN; TF; Pathways; GO; MF; TSG; Functional prioritization; MTPA; BP; transcription factor; Protein–Protein Interaction Network; Gene Ontology—Cellular Component; Gene Ontology—Biology Process; miRNA target prediction algorithms; Gene Ontology—Molecular Function; tissue specific genes; Gene Ontology
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2013.09.106

MicroRNAs (miRNAs) are a class of non-coding RNAs known to play important regulatory roles through targets, which can affect human cell proliferation, differentiation, and metabolism. Overlaps between different miRNA target prediction algorithms (MTPAs) are small, which limit the understanding of miRNA's biological functions. However, the overlaps increase on functional levels, such as Gene Ontology (GO), Protein–Protein Interaction Network (PPIN) and pathways. Here, we performed prioritization on existing predicted target sets for each miRNA by considering all the possible combinations of 7 functional levels. After analyzing the results of both single and multiple functional levels, we found that functional combination strategies including pathways and GO performed better in the prioritization of human miRNA target. The combination which performed best was “Pathway+GO BP+GO MF+GO CC+Target+PPIN”. For the prioritized result of this combination, the valid target had top ranking, and our method performed better than the MTPAs after comparison adopting the validated ranking levels. Top genes in ranking lists generated by this strategy were either validated by experiments or share same functions with the corresponding miRNA/its validated genes in disease related biological processes. •We performed prioritization on miRNA's target by combining 7 functional levels.•We selected the existing predicted target genes for the prioritization.•The functional combination for prioritization was effective.•Combination of pathways and GO performed better in the prioritization.•Top prior genes were validated experimentally or share same biological processes.