Sürdürülebilir Yeşil Kampüs Koleksiyonu / Sustainable Green Campus Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7755

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  • Article
    Citation - WoS: 11
    Citation - Scopus: 14
    Categorization of Species Based on Their Micrornas Employing Sequence Motifs, Information-Theoretic Sequence Feature Extraction, and K-Mers
    (Springer Verlag, 2017) Yousef, Malik; Nigatu, Dawit; Levy, Dalit; Allmer, Jens; Henkel, Werner
    Background: Diseases like cancer can manifest themselves through changes in protein abundance, and microRNAs (miRNAs) play a key role in the modulation of protein quantity. MicroRNAs are used throughout all kingdoms and have been shown to be exploited by viruses to modulate their host environment. Since the experimental detection of miRNAs is difficult, computational methods have been developed. Many such tools employ machine learning for pre-miRNA detection, and many features for miRNA parameterization have been proposed. To train machine learning models, negative data is of importance yet hard to come by; therefore, we recently started to employ pre-miRNAs from one species as positive data versus another species’ pre-miRNAs as negative examples based on sequence motifs and k-mers. Here, we introduce the additional usage of information-theoretic (IT) features. Results: Pre-miRNAs from one species were used as positive and another species’ pre-miRNAs as negative training data for machine learning. The categorization capability of IT and k-mer features was investigated. Both feature sets and their combinations yielded a very high accuracy, which is as good as the previously suggested sequence motif and k-mer based method. However, for obtaining a high performance, a sufficiently large phylogenetic distance between the species and sufficiently high number of pre-miRNAs in the training set is required. To examine the contribution of the IT and k-mer features, an information gain-based feature ranking was performed. Although the top 3 are IT features, 80% of the top 100 features are k-mers. The comparison of all three individual approaches (motifs, IT, and k-mers) shows that the distinction of species based on their pre-miRNAs k-mers are sufficient. Conclusions: IT sequence feature extraction enables the distinction among species and is less computationally expensive than motif calculations. However, since IT features need larger amounts of data to have enough statistics for producing highly accurate results, future categorization into species can be effectively done using k-mers only. The biological reasoning for this is the existence of a codon bias between species which can, at least, be observed in exonic miRNAs. Future work in this direction will be the ab initio detection of pre-miRNA. In addition, prediction of pre-miRNA from RNA-seq can be done.
  • Article
    Citation - WoS: 19
    Citation - Scopus: 29
    One Step Forward, Two Steps Back; Xeno-Micrornas Reported in Breast Milk Are Artifacts
    (Public Library of Science, 2016) Bağcı, Caner; Allmer, Jens
    Background: MicroRNAs (miRNAs) are short RNA sequences that guide post-transcriptional regulation of gene expression via complementarity to their target mRNAs. Discovered only recently, miRNAs have drawn a lot of attention. Multiple protein complexes interact to first cleave a hairpin from nascent RNA, export it into the cytosol, trim its loop, and incorporate it into the RISC complex which is important for binding its target mRNA. This process works within one cell, but circulating miRNAs have been described suggesting a role in cell-cell communication. Motivation: Viruses and intracellular parasites like Toxoplasma gondii use miRNAs to manipulate host gene expression from within the cellular environment. However, recent research has claimed that a rice miRNA may regulate human gene expression. Despite ongoing debates about these findings and general reluctance to accept them, a recent report claimed that foodborne plant miRNAs pass through the digestive tract, travel through blood to be incorporated by alveolar cells excreting milk. The miRNAs are then said to have some immunerelated function in the newborn. Principal Findings: We acquired the data that supports their claim and performed further analyses. In addition to the reported miRNAs, we were able to detect almost complete mRNAs and found that the foreign RNA expression profiles among samples are exceedingly similar. Inspecting the source of the data helped understand how RNAs could contaminate the samples. Conclusion: Viewing these findings in context with the difficulties foreign RNAs face on their route into breast milk and the fact that many identified foodborne miRNAs are not from actual food sources, we can conclude beyond reasonable doubt that the original claims and evidence presented may be due to artifacts. We report that the study claiming their existence is more likely to have detected RNA contamination than miRNAs.