共查询到20条相似文献,搜索用时 31 毫秒
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Background
Many computational microRNA target prediction tools are focused on several key features, including complementarity to 5′seed of miRNAs and evolutionary conservation. While these features allow for successful target identification, not all miRNA target sites are conserved and adhere to canonical seed complementarity. Several studies have propagated the use of energy features of mRNA:miRNA duplexes as an alternative feature. However, different independent evaluations reported conflicting results on the reliability of energy-based predictions. Here, we reassess the usefulness of energy features for mammalian target prediction, aiming to relax or eliminate the need for perfect seed matches and conservation requirement.Methodology/Principal Findings
We detect significant differences of energy features at experimentally supported human miRNA target sites and at genome-wide sites of AGO protein interaction. This trend is confirmed on datasets that assay the effect of miRNAs on mRNA and protein expression changes, and a simple linear regression model leads to significant correlation of predicted versus observed expression change. Compared to 6-mer seed matches as baseline, application of our energy-based model leads to ∼3–5-fold enrichment on highly down-regulated targets, and allows for prediction of strictly imperfect targets with enrichment above baseline.Conclusions/Significance
In conclusion, our results indicate significant promise for energy-based miRNA target prediction that includes a broader range of targets without having to use conservation or impose stringent seed match rules. 相似文献3.
Martin Sturm Michael Hackenberg David Langenberger Dmitrij Frishman 《BMC bioinformatics》2010,11(1):292
Background
Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. 相似文献4.
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Sungsam?Gong Changbum?Park Hansol?Choi Junsu?Ko Insoo?Jang Jungsul?Lee Dan?M?Bolser Donghoon?Oh Deok-Soo?Kim Jong?Bhak
Background
Most proteins function by interacting with other molecules. Their interaction interfaces are highly conserved throughout evolution to avoid undesirable interactions that lead to fatal disorders in cells. Rational drug discovery includes computational methods to identify the interaction sites of lead compounds to the target molecules. Identifying and classifying protein interaction interfaces on a large scale can help researchers discover drug targets more efficiently. 相似文献8.
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Xiaochen Bo Shaoke Lou Daochun Sun Wenjie Shu Jing Yang Shengqi Wang 《BMC bioinformatics》2006,7(1):122-12
Background
Local structures of target mRNAs play a significant role in determining the efficacies of antisense oligonucleotides (ODNs), but some structure-based target site selection methods are limited by uncertainties in RNA secondary structure prediction. If all the predicted structures of a given mRNA within a certain energy limit could be used simultaneously, target site selection would obviously be improved in both reliability and efficiency. In this study, some key problems in ODN target selection on the basis of multiple predicted target mRNA structures are systematically discussed. 相似文献13.
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Background
Regulatory antisense RNAs are a class of ncRNAs that regulate gene expression by prohibiting the translation of an mRNA by establishing stable interactions with a target sequence. There is great demand for efficient computational methods to predict the specific interaction between an ncRNA and its target mRNA(s). There are a number of algorithms in the literature which can predict a variety of such interactions - unfortunately at a very high computational cost. Although some existing target prediction approaches are much faster, they are specialized for interactions with a single binding site. 相似文献15.
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Narendra P. Singh Udai P. Singh Hongbing Guan Prakash Nagarkatti Mitzi Nagarkatti 《PloS one》2012,7(9)
Background
MicroRNAs (miRs) are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), an environmental contaminant is well known to induce severe toxicity (acute and chronic) with long-term effects. Also, in utero exposure of fetus to TCDD has been shown to cause thymic atrophy and alterations in T cell differentiation. It is also relevant to understand “the fetal basis of adult disease” hypothesis, which proposes that prenatal exposure to certain forms of nutritional and environmental stress can cause increased susceptibility to clinical disorders later in life. In the current study, therefore, we investigated the effects of prenatal exposure to TCDD on miR profile in fetal thymocytes and searched for their possible role in causing thymic atrophy and alterations in the expression of apoptotic genes.Methodology/Principal Findings
miR arrays of fetal thymocytes post exposure to TCDD and vehicle were performed. Of the 608 mouse miRs screened, 78 miRs were altered more than 1.5 fold and 28 miRs were changed more than 2 fold in fetal thymocytes post-TCDD exposure when compared to vehicle controls. We validated the expression of several of the miRs using RT-PCR. Furthermore, several of the miRs that were downregulated contained highly complementary sequence to the 3′-UTR region of AhR, CYP1A1, Fas and FasL. Also, the Ingenuity Pathway Analysis software and database was used to analyze the 78 miRs that exhibited significant expression changes and revealed that as many as 15 pathways may be affected.Conclusions/Significance
These studies revealed that TCDD-mediated alterations in miR expression may be involved in the regulation of its toxicity including cancer, hepatic injury, apoptosis, and cellular development. 相似文献17.
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C. Feng S. Mansouri B.H. Bluhm L.J. du Toit J.C. Correll 《Journal of applied microbiology》2014,117(2):472-484