期刊
PLOS COMPUTATIONAL BIOLOGY
卷 5, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pcbi.1000516
关键词
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资金
- National Cancer Institute [T32 CA 09565, R01 CA64364]
- National Eye Institute [T32 EY007119]
- Amgen Inc. [MEAM06-33571]
- National Library of Medicine [NLM 2T15LM007359]
- NATIONAL CANCER INSTITUTE [T32CA009565, R01CA064364] Funding Source: NIH RePORTER
- NATIONAL EYE INSTITUTE [T32EY007119] Funding Source: NIH RePORTER
- NATIONAL LIBRARY OF MEDICINE [T15LM007359] Funding Source: NIH RePORTER
MicroRNAs (miRNAs) posttranscriptionally regulate targeted messenger RNAs (mRNAs) by inducing cleavage or otherwise repressing their translation. We address the problem of detecting m/miRNA targeting relationships in homo sapiens from microarray data by developing statistical models that are motivated by the biological mechanisms used by miRNAs. The focus of our modeling is the construction, activity, and mediation of RNA-induced silencing complexes (RISCs) competent for targeted mRNA cleavage. We demonstrate that regression models accommodating RISC abundance and controlling for other mediating factors fit the expression profiles of known target pairs substantially better than models based on m/miRNA expressions alone, and lead to verifications of computational target pair predictions that are more sensitive than those based on marginal expression levels. Because our models are fully independent of exogenous results from sequence-based computational methods, they are appropriate for use as either a primary or secondary source of information regarding m/miRNA target pair relationships, especially in conjunction with high-throughput expression studies.
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