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Genome-wide discovery of miRNAs using ensembles of machine learning algorithms and logistic regression
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. (Bioinformatik)ORCID iD: 0000-0001-9242-4852
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. (Tumörbiologi)
University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience. (Bioinformatic)ORCID iD: 0000-0001-6254-4335
2015 (English)In: International Journal of Data Mining and Bioinformatics, ISSN 1748-5681, Vol. 13, no 4, 338-359 p.Article in journal (Refereed) Published
Abstract [en]

In silico prediction of novel miRNAs from genomic sequences remains a challenging problem. This study presents a genome-wide miRNA discovery software package called GenoScan and evaluates two hairpin classification methods. These methods, one ensemble-based and one using logistic regression were benchmarked along with 15 published methods. In addition, the sequence-folding step is addressed by investigating the impact of secondary structure prediction methods and the choice of input sequence length on prediction performance. Both the accuracy of secondary structure predictions and the miRNA prediction are evaluated. In the benchmark of hairpin classification methods, the regression model achieved highest classification accuracy. Of the structure prediction methods evaluated, ContextFold achieved the highest agreement between predicted and experimentally determined structures. However, both the choice of secondary structure prediction method and input sequence length had limited impact on hairpin classification performance.

Place, publisher, year, edition, pages
InderScience Publishers, 2015. Vol. 13, no 4, 338-359 p.
National Category
Bioinformatics and Systems Biology
Research subject
Natural sciences
URN: urn:nbn:se:his:diva-11759DOI: 10.1504/IJDMB.2015.072755ISI: 000366135400002PubMedID: 26547983ScopusID: 2-s2.0-84946741012OAI: diva2:882854
Available from: 2015-12-15 Created: 2015-12-15 Last updated: 2016-01-25Bibliographically approved
In thesis
1. Bioinformatics tools for discovery and evaluation of biomarkers: Applications in clinical assessment of cancer
Open this publication in new window or tab >>Bioinformatics tools for discovery and evaluation of biomarkers: Applications in clinical assessment of cancer
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cancer is a disease characterized by abnormal proliferation of cells in the body and ranks as the second leading cause of death worldwide. In order to improve cancer patient care, a major focus of cancer research is to discover biomarkers. A biomarker is a biological molecule found in tissues or body fluids and can be used to predict or assess disease states. The aim of this thesis is to develop bioinformatics tools for discovery and evaluation of novel biomarkers from high-throughput datasets.

MicroRNAs (miRNAs) are short non-coding RNAs that function as negative regulators of gene expression. Dysregulation of miRNAs in cancer is frequently reported, making them interesting as biomarker candidates. GenoScan was developed for genome-wide discovery of miRNA-coding genes, as a first step in the identification of novel mi-RNA biomarkers.

High-throughput technologies such as microarrays allow researchers to measure the expression of thousands of genes or miRNAs simultaneously. The Decision Trunk Classifier (DTC) algorithm has been developed to screen datasets from these experiments for biomarker candidates. When applied to a miRNA expression dataset for endometrial cancer (EC) samples vs. controls, a two-marker model with 98 % accuracy was generated. These miRNAs (hsa-miR-183-5p and hsa-miRPlus-C1070) are promising as biomarkers for EC screening.

The miREC database was developed to store gene and miRNA data from curated expression profiling studies of EC, as well as gene-miRNA regulatory connections. Using gene-miRNA interaction networks from miREC, the roles of miRNAs in cancer hallmark acquisition can be clarified. To further support exploratory analysis of expression data, DTC was extended with partial least squares regression models. The resulting PLS-DTC algorithm can be used to gain deeper insights into the perturbation of biological processes and pathways.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2016. 75 p.
, Örebro Studies in Medicine, ISSN 1652-4063 ; 130
Algorithms, biomarkers, machine learning, classification, cancer, microRNA database, microRNA discovery, partial least squares
National Category
Medical and Health Sciences
Research subject
Medical sciences
urn:nbn:se:his:diva-11824 (URN)978-91-7529-111-6 (ISBN)
Public defence
2016-02-03, Insikten (Portalen), Skövde, 23:05 (English)
Available from: 2016-01-22 Created: 2016-01-12 Last updated: 2016-01-22Bibliographically approved

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Ulfenborg, BenjaminKlinga-Levan, KarinOlsson, Björn
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