Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Conference Object Citation - WoS: 3Citation - Scopus: 8Distinguishing Between Microrna Targets From Diverse Species Using Sequence Motifs and K-Mers(SCITEPRESS, 2017) Yousef, Malik; Khalifa, Waleed; Acar, İlhan Erkin; Allmer, JensA disease phenotype is often due to dysregulation of gene expression. Post-translational regulation of protein abundance by microRNAs (miRNAs) is, therefore, of high importance in, for example, cancer studies. MicroRNAs provide a complementary sequence to their target messenger RNA (mRNA) as part of a complex molecular machinery. Known miRNAs and targets are listed in miRTarBase for a variety of organisms. The experimental detection of such pairs is convoluted and, therefore, their computational detection is desired which is complicated by missing negative data. For machine learning, many features for parameterization of the miRNA targets are available and k-mers and sequence motifs have previously been used. Unrelated organisms like intracellular pathogens and their hosts may communicate via miRNAs and, therefore, we investigated whether miRNA targets from one species can be differentiated from miRNA targets of another. To achieve this end, we employed target information of one species as positive and the other as negative training and testing data. Models of species with higher evolutionary distance generally achieved better results of up to 97% average accuracy (mouse versus Caenorhabditis elegans) while more closely related species did not lead to successful models (human versus mouse; 60%). In the future, when more targeting data becomes available, models can be established which will be able to more precisely determine miRNA targets in hostpathogen systems using this approach.Article Citation - WoS: 20Citation - Scopus: 25Microrna Categorization Using Sequence Motifs and K-Mers(BioMed Central Ltd., 2017) Yousef, Malik; Khalifa, Waleed; Acar, İlhan Erkin; Allmer, JensBackground: Post-transcriptional gene dysregulation can be a hallmark of diseases like cancer and microRNAs (miRNAs) play a key role in the modulation of translation efficiency. Known pre-miRNAs are listed in miRBase, and they have been discovered in a variety of organisms ranging from viruses and microbes to eukaryotic organisms. The computational detection of pre-miRNAs is of great interest, and such approaches usually employ machine learning to discriminate between miRNAs and other sequences. Many features have been proposed describing pre-miRNAs, and we have previously introduced the use of sequence motifs and k-mers as useful ones. There have been reports of xeno-miRNAs detected via next generation sequencing. However, they may be contaminations and to aid that important decision-making process, we aimed to establish a means to differentiate pre-miRNAs from different species. Results: To achieve distinction into species, we used one species' pre-miRNAs as the positive and another species' pre-miRNAs as the negative training and test data for the establishment of machine learned models based on sequence motifs and k-mers as features. This approach resulted in higher accuracy values between distantly related species while species with closer relation produced lower accuracy values. Conclusions: We were able to differentiate among species with increasing success when the evolutionary distance increases. This conclusion is supported by previous reports of fast evolutionary changes in miRNAs since even in relatively closely related species a fairly good discrimination was possible.Article Citation - WoS: 14Citation - Scopus: 12The Impact of Feature Selection on One and Two-Class Classification Performance for Plant Micrornas(PeerJ Inc., 2016) Khalifa, Waleed; Yousef, Malik; Saçar Demirci, Müşerref Duygu; Allmer, JensMicroRNAs (miRNAs) are short nucleotide sequences that form a typical hairpin structure which is recognized by a complex enzyme machinery. It ultimately leads to the incorporation of 18-24 nt long mature miRNAs into RISC where they act as recognition keys to aid in regulation of target mRNAs. It is involved to determine miRNAs experimentally and, therefore, machine learning is used to complement such endeavors. The success of machine learning mostly depends on proper input data and appropriate features for parameterization of the data. Although, in general, two-class classification (TCC) is used in the field; because negative examples are hard to come by, one-class classification (OCC) has been tried for pre-miRNA detection. Since both positive and negative examples are currently somewhat limited, feature selection can prove to be vital for furthering the field of pre-miRNA detection. In this study, we compare the performance of OCC and TCC using eight feature selection methods and seven different plant species providing positive pre-miRNA examples. Feature selection was very successful for OCC where the best feature selection method achieved an average accuracy of 95.6%, thereby being ~29% better than the worst method which achieved 66.9% accuracy. While the performance is comparable to TCC, which performs up to 3% better than OCC, TCC is much less affected by feature selection and its largest performance gap is ~13% which only occurs for two of the feature selection methodologies. We conclude that feature selection is crucially important for OCC and that it can perform on par with TCC given the proper set of features.Conference Object Citation - Scopus: 13Feature Selection for Microrna Target Prediction Comparison of One-Class Feature Selection Methodologies(Hindawi Publishing Corporation, 2016) Yousef, Malik; Allmer, Jens; Khalifa, WaleedTraditionally, machine learning algorithms build classification models from positive and negative examples. Recently, one-class classification (OCC) receives increasing attention in machine learning for problems where the negative class cannot be defined unambiguously. This is specifically problematic in bioinformatics since for some important biological problems the target class (positive class) is easy to obtain while the negative one cannot be measured. Artificially generating the negative class data can be based on unreliable assumptions. Several studies have applied two-class machine learning to predict microRNAs (miRNAs) and their target. Different approaches for the generation of an artificial negative class have been applied, but may lead to a biased performance estimate. Feature selection has been well studied for the two-class classification problem, while fewer methods are available for feature selection in respect to OCC. In this study, we present a feature selection approach for applying one-class classification to the prediction of miRNA targets. A comparison between one-class and two-class approaches is presented to highlight that their performance are similar while one-class classification is not based on questionable artificial data for training and performance evaluation. We further show that the feature selection method we tried works to a degree, but needs improvement in the future. Perhaps it could be combined with other approaches.Article Citation - Scopus: 19Feature Selection Has a Large Impact on One-Class Classification Accuracy for Micrornas in Plants(Hindawi Publishing Corporation, 2016) Yousef, Malik; Demirci, Müşerref Duygu Saçar; Khalifa, Waleed; Allmer, JensMicroRNAs (miRNAs) are short RNA sequences involved in posttranscriptional gene regulation. Their experimental analysis is complicated and, therefore, needs to be supplemented with computational miRNA detection. Currently computational miRNA detection is mainly performed using machine learning and in particular two-class classification. For machine learning, the miRNAs need to be parametrized and more than 700 features have been described. Positive training examples for machine learning are readily available, but negative data is hard to come by. Therefore, it seems prerogative to use one-class classification instead of two-class classification. Previously, we were able to almost reach two-class classification accuracy using one-class classifiers. In this work, we employ feature selection procedures in conjunction with one-class classification and show that there is up to 36% difference in accuracy among these feature selection methods. The best feature set allowed the training of a one-class classifier which achieved an average accuracy of 95.6% thereby outperforming previous two-class-based plant miRNA detection approaches by about 0.5%. We believe that this can be improved upon in the future by rigorous filtering of the positive training examples and by improving current feature clustering algorithms to better target pre-miRNA feature selection.