Showing papers by "Jens Allmer published in 2019"

maTE: discovering expressed interactions between microRNAs and their targets.

Abstract: MOTIVATION Disease is often manifested via changes in transcript and protein abundance. MicroRNAs (miRNAs) are instrumental in regulating protein abundance and may measurably influence transcript levels. miRNAs often target more than one mRNA (for humans, the average is three), and mRNAs are often targeted by more than one miRNA (for the genes considered in this study, the average is also three). Therefore, it is difficult to determine the miRNAs that may cause the observed differential gene expression. We present a novel approach, maTE, which is based on machine learning, that integrates information about miRNA target genes with gene expression data. maTE depends on the availability of a sufficient amount of patient and control samples. The samples are used to train classifiers to accurately classify the samples on a per miRNA basis. Multiple high scoring miRNAs are used to build a final classifier to improve separation. RESULTS The aim of the study is to find a set of miRNAs causing the regulation of their target genes that best explains the difference between groups (e.g. cancer versus control). maTE provides a list of significant groups of genes where each group is targeted by a specific miRNA. For the datasets used in this study, maTE generally achieves an accuracy well above 80%. Also, the results show that when the accuracy is much lower (e.g. ∼50%), the set of miRNAs provided is likely not causative of the difference in expression. This new approach of integrating miRNA regulation with expression data yields powerful results and is independent of external labels and training data. Thereby, this approach allows new avenues for exploring miRNA regulation and may enable the development of miRNA-based biomarkers and drugs. AVAILABILITY AND IMPLEMENTATION The KNIME workflow, implementing maTE, is available at Bioinformatics online. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

Computational Prediction of Functional MicroRNA-mRNA Interactions.

Abstract: Proteins have a strong influence on the phenotype and their aberrant expression leads to diseases. MicroRNAs (miRNAs) are short RNA sequences which posttranscriptionally regulate protein expression. This regulation is driven by miRNAs acting as recognition sequences for their target mRNAs within a larger regulatory machinery. A miRNA can have many target mRNAs and an mRNA can be targeted by many miRNAs which makes it difficult to experimentally discover all miRNA-mRNA interactions. Therefore, computational methods have been developed for miRNA detection and miRNA target prediction. An abundance of available computational tools makes selection difficult. Additionally, interactions are not currently the focus of investigation although they more accurately define the regulation than pre-miRNA detection or target prediction could perform alone. We define an interaction including the miRNA source and the mRNA target. We present computational methods allowing the investigation of these interactions as well as how they can be used to extend regulatory pathways. Finally, we present a list of points that should be taken into account when investigating miRNA-mRNA interactions. In the future, this may lead to better understanding of functional interactions which may pave the way for disease marker discovery and design of miRNA-based drugs.

Detection of pre-microRNA with Convolutional Neural Networks

Abstract: MicroRNAs (miRNAs) are small non-coding RNA sequences that have been implicated in many physiological processes. Furthermore, miRNAs have been shown to be important biomarkers for diseases and their mimics are tested as drug candidates. The experimental discovery of miRNAs is complicated because both miRNAs and their targets need to be expressed for the confirmation of functional interaction. This is difficult since miRNA expression is under spatiotemporal control. This has motivated the development of computational methods for miRNA detection. Such computational methods typically involve the characterization of candidate sequences with features designed by domain experts and the application of statistical or machine learning algorithms. While such features can successfully encode domain knowledge, feature engineering is a difficult and time consuming task. Additionally, some engineered features pose excessive computational complexity that can hinder the large scale detection of miRNA. In contrast, advances of representation learning methods such as deep learning provide for automatic development of effective features directly from data. In this work, we propose a method that uses domain knowledge to create an efficient image representation of miRNA molecules encoding sequence, structure, and implicitly some thermodynamic information. We then use this low-level feature representation of the molecules to develop a hierarchical deep representation using a convolutional neural network model, which directly detects precursor miRNAs. With this method we achieve state-of-the-art performance on all previously used datasets. Additionally, detection is achieved in real time thereby overcoming the high computational cost for current pre-miRNA feature calculations such as p-value based ones. Finally, the encoding and modeling process opens possibilities for interpretability of the models9 behavior, which may lead to novel biological interpretations of miRNA genesis and targeting.

Towards an Internet of Science.

Abstract: Big data and complex analysis workflows (pipelines) are common issues in data driven science such as bioinformatics. Large amounts of computational tools are available for data analysis. Additionally, many workflow management systems to piece together such tools into data analysis pipelines have been developed. For example, more than 50 computational tools for read mapping are available representing a large amount of duplicated effort. Furthermore, it is unclear whether these tools are correct and only a few have a user base large enough to have encountered and reported most of the potential problems. Bringing together many largely untested tools in a computational pipeline must lead to unpredictable results. Yet, this is the current state. While presently data analysis is performed on personal computers/workstations/clusters, the future will see development and analysis shift to the cloud. None of the workflow management systems is ready for this transition. This presents the opportunity to build a new system, which will overcome current duplications of effort, introduce proper testing, allow for development and analysis in public and private clouds, and include reporting features leading to interactive documents.

Classification of Pre-cursor microRNAs from Different Species Using a New Set of Features.

Abstract: MicroRNAs (miRNAs) are short RNA sequences actively involved in post-transcriptional gene regulation. Such miRNAs have been discovered in most eukaryotic organisms. They also seem to exist in viruses and perhaps in microbial pathogens to target the host. Drosha is the enzyme which first cleaves the pre-miRNA from the nascent pri-miRNA. Previously, we showed that it is possible to distinguish between pre-miRNAs of different species depending on their evolutionary distance using just k-mers.

Classification of Pre-cursor microRNAs from Different Species Using a New Set of Features

Abstract: MicroRNAs (miRNAs) are short RNA sequences actively involved in post-transcriptional gene regulation. Such miRNAs have been discovered in most eukaryotic organisms. They also seem to exist in viruses and perhaps in microbial pathogens to target the host. Drosha is the enzyme which first cleaves the pre-miRNA from the nascent pri-miRNA. Previously, we showed that it is possible to distinguish between pre-miRNAs of different species depending on their evolutionary distance using just k-mers.