Use of MicroRNAs in Personalized Medicine

Avci, Çığır Biray; Baran, Yusuf

doi:10.1007/978-1-62703-748-8_19

Cited by 17 publications

(9 citation statements)

References 108 publications

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“…The assessment of host and pathogen miRNA responses is an exciting area of investigation, both for improving our understanding of viral pathogenesis, and for developing biomarkers and therapeutic targets . This is especially true for CMV infection after transplantation, where the complex interaction between viral and host factors contribute to pathogenesis, and where current preventive and treatment strategies have been only partially successful.…”

Section: Discussionmentioning

confidence: 99%

Hcmv-miR-UL22A-5p: A Biomarker in Transplantation With Broad Impact on Host Gene Expression and Potential Immunological Implications

Lisboa

Egli

Nicholls

et al. 2015

American Journal of Transplantation

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Cytomegalovirus (CMV) encodes multiple microRNAs. While these have been partially characterized in vitro, their relevance to clinical CMV infection has not been evaluated. We analyzed samples from a cohort of solid organ transplant patients with CMV disease (n = 245) for viral microRNA expression. Several CMV microRNAs were readily detectable in patients with CMV disease in variable relative abundance. Expression level generally correlated with DNA viral load and the absence of viral microRNA was associated with faster viral clearance. Detection of hcmv-miR-UL22A-5p at baseline independently predicted the recurrence of CMV viremia upon discontinuation of antiviral therapy (OR 3.024, 95% CI: 1.35-6.8; p = 0.007). A combination of direct mRNA targeting by the microRNA and indirect modulation of gene expression involving isoforms of the transcriptional regulator C-MYC may be responsible for the broad effects seen in the association of gene transcripts with the RNA-induced silencing complex and in global protein expression upon hcmv-miR-UL22A-5p transfection. This novel study of in vivo viral microRNA expression profiles provides unique insight into the complexity of clinical CMV infection following transplantation. We provide evidence that viral microRNAs may have complex effects on gene expression and be associated with specific virologic and clinical outcomes, and thus could be further evaluated as biomarkers.

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Section: Discussionmentioning

confidence: 99%

Hcmv-miR-UL22A-5p: A Biomarker in Transplantation With Broad Impact on Host Gene Expression and Potential Immunological Implications

Lisboa

Egli

Nicholls

et al. 2015

American Journal of Transplantation

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“…Dysregulation of miRNAs is a hallmark of diseases; among them cancer 9 , that makes miRNAs interesting as biomarkers 10 , even more so since they are often detectable in bodily fluids 11 and thus are accessible with low-invasive methods. Modulation of miRNA abundances may lead to therapeutics 12 that may prove to be especially useful in personalized medicine 13 . Particularly when taking into account miRNAs’ possible roles in cell-cell (circulating miRNAs) 14 and pathogen-host communication 15 .…”

Section: Introductionmentioning

confidence: 99%

On the performance of pre-microRNA detection algorithms

2017

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MicroRNAs are crucial for post-transcriptional gene regulation, and their dysregulation has been associated with diseases like cancer and, therefore, their analysis has become popular. The experimental discovery of miRNAs is cumbersome and, thus, many computational tools have been proposed. Here we assess 13 ab initio pre-miRNA detection approaches using all relevant, published, and novel data sets while judging algorithm performance based on ten intrinsic performance measures. We present an extensible framework, izMiR, which allows for the unbiased comparison of existing algorithms, adding new ones, and combining multiple approaches into ensemble methods. In an exhaustive attempt, we condense the results of millions of computations and show that no method is clearly superior; however, we provide a guideline for biomedical researchers to select a tool. Finally, we demonstrate that combining all of the methods into one ensemble approach, for the first time, allows reliable purely computational pre-miRNA detection in large eukaryotic genomes.

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“…The latter reduces the impact of intrinsic miRNAs by providing an abundance of target sequences effectively reducing the amount of interactions with mRNAs. Such approaches have been tested for example in human (Avci and Baran, 2014 ) and since T. gondii exchanges vesicles with its hosts (Romano and Coppens, 2013 ), drugs may be delivered to the parasite via the host system. Knowledge about the interactions in different stages of T. gondii development and within different hosts will enable the design of miRNA mimics and decoys by showing their availability and differential distribution.…”

Section: Discussionmentioning

confidence: 99%

“…So far, existing treatment has major limitations and targets only the replicative tachyzoite stage by mainly inducing tachyzoite-bradyzoite conversion thereby promoting parasite persistence (Montazeri et al, 2017 ). MicroRNAs (miRNAs) have been established as disease targets (Avci and Baran, 2014 ) and miRNA mimics as drugs (Wang, 2011 ) and they may be of use to target toxoplasmosis. MicroRNAs are short non-coding sequences involved in post-transcriptional regulation of protein expression.…”

Section: Introductionmentioning

confidence: 99%

The Expressed MicroRNA—mRNA Interactions of Toxoplasma gondii

et al. 2018

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MicroRNAs (miRNAs) are involved in post-transcriptional modulation of gene expression and thereby have a large influence on the resulting phenotype. We have previously shown that miRNAs may be involved in the communication between Toxoplasma gondii and its hosts and further confirmed a number of proposed specific miRNAs. Yet, little is known about the internal regulation via miRNAs in T. gondii. Therefore, we predicted pre-miRNAs directly from the type II ME49 genome and filtered them. For the confident hairpins, we predicted the location of the mature miRNAs and established their target genes. To add further confidence, we evaluated whether the hairpins and their targets were co-expressed. Such co-expressed miRNA and target pairs define a functional interaction. We extracted all such functional interactions and analyzed their differential expression among strains of all three clonal lineages (RH, PLK, and CTG) and between the two stages present in the intermediate host (tachyzoites and bradyzoites). Overall, we found ~65,000 expressed interactions of which ~5,500 are differentially expressed among strains but none are significantly differentially expressed between developmental stages. Since miRNAs and target decoys can be used as therapeutics we believe that the list of interactions we provide will lead to novel approaches in the treatment of toxoplasmosis.

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Use of MicroRNAs in Personalized Medicine

Cited by 17 publications

References 108 publications

Hcmv-miR-UL22A-5p: A Biomarker in Transplantation With Broad Impact on Host Gene Expression and Potential Immunological Implications

Hcmv-miR-UL22A-5p: A Biomarker in Transplantation With Broad Impact on Host Gene Expression and Potential Immunological Implications

On the performance of pre-microRNA detection algorithms

The Expressed MicroRNA—mRNA Interactions of Toxoplasma gondii

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