Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
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Book Part Citation - Scopus: 444 Current Challenges in Mirnomics(Humana Press, 2022) Akgül, Bünyamin; Stadler, Peter F.; Hawkins, Liam J.; Hadj-Moussa, Hanane; Storey, Kenneth B.; Ergin, Kemal; Allmer, JensMature microRNAs (miRNAs) are short RNA sequences about 18–24 nucleotide long, which provide the recognition key within RISC for the posttranscriptional regulation of target RNAs. Considering the canonical pathway, mature miRNAs are produced via a multistep process. Their transcription (pri-miRNAs) and first processing step via the microprocessor complex (pre-miRNAs) occur in the nucleus. Then they are exported into the cytosol, processed again by Dicer (dsRNA) and finally a single strand (mature miRNA) is incorporated into RISC (miRISC). The sequence of the incorporated miRNA provides the function of RNA target recognition via hybridization. Following binding of the target, the mRNA is either degraded or translation is inhibited, which ultimately leads to less protein production. Conversely, it has been shown that binding within the 5? UTR of the mRNA can lead to an increase in protein product. Regulation of homeostasis is very important for a cell; therefore, all steps in the miRNA-based regulation pathway, from transcription to the incorporation of the mature miRNA into RISC, are under tight control. While much research effort has been exerted in this area, the knowledgebase is not sufficient for accurately modelling miRNA regulation computationally. The computational prediction of miRNAs is, however, necessary because it is not feasible to investigate all possible pairs of a miRNA and its target, let alone miRNAs and their targets. We here point out open challenges important for computational modelling or for our general understanding of miRNA-based regulation and show how their investigation is beneficial. It is our hope that this collection of challenges will lead to their resolution in the near future. © 2022, Springer Science+Business Media, LLC, part of Springer Nature.Letter Citation - Scopus: 9A Call for Benchmark Data in Mass Spectrometry-Based Proteomics(Proteomass Scientific Society, 2012) Allmer, JensProteomics is a quickly developing field. New and better mass spectrometers, the platform of choice in proteomics, are being introduced frequently. New algorithms for the analysis of mass spectrometric data and assignment of amino acid sequence to tandem mass spectra are also presented on a frequent basis. Unfortunately, the best application area for these algorithms cannot be established at the moment. Furthermore, even the accuracy of the algorithms and their relative performance cannot be established. This is due to the lack of proper benchmark data. This letter first introduces the field of mass spectrometry-based proteomics and then defines the expectations of a well-designed benchmark dataset. Thereafter, the current situation is compared to this ideal. A call for the creation of a proper benchmark dataset is then placed and it is explained how measurement should be performed. Finally, the benefits for the research community are highlighted. © 2012, Proteomass Scientific Society. All rights reserved.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.Book Part Citation - Scopus: 9Differential Expression of Toxoplasma Gondii Micrornas in Murine and Human Hosts(Springer, 2016) Allmer, Jens; Saçar Demirci, Müşerref Duygu; Bağcı, CanerMicroRNAs are short RNA sequences involved in post-transcriptional gene regulation. MicroRNAs are known for a wide variety of species ranging from bacteria to plants. It has become clear that some cross-kingdom regulation is possible especially between viruses and their hosts. We hypothesized that intracellular parasites, like Toxoplasma gondii, similar to viruses would be able to modulate their host’s gene expression. We were able to show that T. gondii produces many putative pre-miRNAs which are actually transcribed. Furthermore, some of these expressed pre-miRNAs have a striking resemblance to host mature miRNAs. Previous studies indicated that T. gondii infection coincides with increased abundance of some miRNAs. Here we were able to show that many of these miRNAs have close relatives in T. gondii which may not be distinguishable using PCR. Taken together, the similarity to host miRNAs, their confirmed expression, and their upregulation during infection, it suggests that T. gondii actively transfers miRNAs to regulate its host. We conclude, that this type of cross-kingdom regulation may be possible, but that targeted analysis is necessary to consolidate our computational findings. © Springer International Publishing Switzerland 2016. All rights are reserved.Article Citation - Scopus: 1Determining the C-Terminal Amino Acid of a Peptide From Ms/Ms Data(Proteomass Scientific Society, 2013) Allmer, JensProteomics is currently chiefly based on mass spectrometry (MS) which is the tool of choice to investigate proteins. Two computational approaches to derive the tandem mass spectrum precursor’s sequence are widely employed. Database search essentially retrieves the sequence by matching the spectrum to all entries in a database whereas de novo sequencing does not depend on a sequence database. Both approaches benefit from knowledge about the enzyme used to generate the peptides. Most algorithms default to trypsin for its abundant usage. Trypsin cuts after arginine and lysine and thus the c-terminal amino acid is not known precisely and usually either of the two. Furthermore, 90% of protein terminal peptides may not end with either arginine or lysine and may thus contain any of the other amino acids. Here an algorithm is presented which predicts the c-terminal amino acid to be arginine, lysine or any other. Here an algorithm, named RKDecider, to sort the c-terminal amino acid into one of three groups (arginine, lysine, and other) is presented. Although around 90% accuracy was achieved during data mining spectra for rules that determine the c-terminal amino acid, the implementation’s (RKDecider) accuracy is a little less and achieves about 80%. This is due to the fact that the decision trees were implemented as a rulebased system for speed considerations. The implementation is freely available at: http://bioinformatics.iyte.edu.tr/RKDecider.Article Citation - WoS: 16Citation - Scopus: 18Computational and Bioinformatics Methods for Microrna Gene Prediction(Humana Press, 2014) Allmer, JensMicroRNAs (miRNAs) have attracted ever-increasing interest in recent years. Since experimental approaches for determining miRNAs are nontrivial in their application, computational methods for the prediction of miRNAs have gained popularity. Such methods can be grouped into two broad categories (1) performing ab initio predictions of miRNAs from primary sequence alone and (2) additionally employing phylogenetic conservation. Most methods acknowledge the importance of hairpin or stem-loop structures and employ various methods for the prediction of RNA secondary structure. Machine learning has been employed in both categories with classification being the predominant method. In most cases, positive and negative examples are necessary for performing classification. Since it is currently elusive to experimentally determine all possible miRNAs for an organism, true negative examples are hard to come by, and therefore the accuracy assessment of algorithms is hampered. In this chapter, first RNA secondary structure prediction is introduced since it provides a basis for miRNA prediction. This is followed by an assessment of homology and then ab initio miRNA prediction methods.Article Citation - WoS: 37Citation - Scopus: 46Computational Methods for Microrna Target Prediction(Humana Press, 2014) Hamzeiy, Hamid; Yousef, Malik; Allmer, JensMicroRNAs (miRNAs) are important players in gene regulation. The final and maybe the most important step in their regulatory pathway is the targeting. Targeting is the binding of the miRNA to the mature RNA via the RNA-induced silencing complex. Expression patterns of miRNAs are highly specific in respect to external stimuli, developmental stage, or tissue. This is used to diagnose diseases such as cancer in which the expression levels of miRNAs are known to change considerably. Newly identified miRNAs are increasing in number with every new release of miRBase which is the main online database providing miRNA sequences and annotation. Many of these newly identified miRNAs do not yet have identified targets. This is especially the case in animals where the miRNA does not bind to its target as perfectly as it does in plants. Valid targets need to be identified for miRNAs in order to properly understand their role in cellular pathways. Experimental methods for target validations are difficult, expensive, and time consuming. Having considered all these facts it is of crucial importance to have accurate computational miRNA target predictions. There are many proposed methods and algorithms available for predicting targets for miRNAs, but only a few have been developed to become available as independent tools and software. There are also databases which collect and store information regarding predicted miRNA targets. Current approaches to miRNA target prediction produce a huge amount of false positive and an unknown amount of false negative results, and thus the need for better approaches is evermore evident. This chapter aims to give some detail about the current tools and approaches used for miRNA target prediction, provides some grounds for their comparison, and outlines a possible future.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.Article Citation - WoS: 30Machine Learning Methods for Microrna Gene Prediction(Humana Press, 2014) Saçar, Müşerref Duygu; Allmer, JensMicroRNAs (miRNAs) are single-stranded, small, noncoding RNAs of about 22 nucleotides in length, which control gene expression at the posttranscriptional level through translational inhibition, degradation, adenylation, or destabilization of their target mRNAs. Although hundreds of miRNAs have been identified in various species, many more may still remain unknown. Therefore, discovery of new miRNA genes is an important step for understanding miRNA-mediated posttranscriptional regulation mechanisms. It seems that biological approaches to identify miRNA genes might be limited in their ability to detect rare miRNAs and are further limited to the tissues examined and the developmental stage of the organism under examination. These limitations have led to the development of sophisticated computational approaches attempting to identify possible miRNAs in silico. In this chapter, we discuss computational problems in miRNA prediction studies and review some of the many machine learning methods that have been tried to address the issues.