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Methods in Molecular Biology 1107 Malik Yousef Jens Allmer Editors miRNomics MicroRNA Biology and Computational Analysis M M B ™ ETHODS IN OLECULAR IOLOGY Series Editor John M. Walker School of Life Sciences University of Hertfordshire Hat fi eld, Hertfordshire, AL10 9AB, UK For further volumes: http://www.springer.com/series/7651 miRNomics: MicroRNA Biology and Computational Analysis Edited by Malik Yousef Dabburiya Village, Israel Jens Allmer Izmir Institute of Technology, Izmir, Turkey Editors Malik Yousef Jens Allmer Dabburiya Village, I srael Izmir Institute of Technology Izmir , Turkey ISSN 1064-3745 ISSN 1940-6029 (electronic) ISBN 978-1-62703-747-1 ISBN 978-1-62703-748-8 (eBook) DOI 10.1007/978-1-62703-748-8 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2013953868 © Springer Science+Business Media New York 2 014 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Humana Press is a brand of Springer Springer is part of Springer Science+Business Media (www.springer.com) Dedication JA dedicates the book to his wife Açalya and his son Lukas Aren who was born during the editing of this book. MY dedicates the book to his parents Mustafa and Haji and his wife Sahar and his daugh- ters Miar and Umaymah and his sons Anas and Mohammed. Pref ace Micro RNAs (miRNAs) have just recently been discovered, but the scientifi c interest is enormous. When we started becoming interested in miRNAs around 2006, there was already a signifi cant body of knowledge to draw from. Of course we don’t work on our own and it is often necessary to introduce students, colleagues, or new collaborators to the current state of miRNA research. Sending out large amounts of review articles is one option but we wanted to improve the situation and decided to put together a book which touches on all the topics relevant to miRNA research. The outcome is what you are currently holding in your hands. We aimed to encompass relevant information from biogenesis of miR- NAs, their biological function, computational analyses, as well as medical implications. Each of these topics may be a book in its own right, and this book neither can nor intends to be exhaustive for any of the subjects that it touches upon. This book is rather intended to present an overview of the current state of the art and aims to put the respective areas of research into a larger perspective. One of the editors is a computer scientist and the other is a biologist by training, and this hopefully ensured that both sides, the computational and the biologic component, are adequately treated in this book but both of us also wanted to highlight medical implications in respect to miRNAs. So if you are coming from the computer science side and want to learn more about the biology of miRNAs, this book will provide the information you need. Likewise, if you come with a biology perspective, you will fi nd computational, statistic, and medical information. The book can be read from the beginning to the end for newcomers to the fi eld but those that fi nd themselves already knowledgeable in parts of miRNA research, statistics, or any other topic tackled in the book can safely skip such chapters. Scientists today are usually overworked and it is diffi cult to fi nd colleagues who are able to spend time to write or review book chapters and no wonder we received many replies to our initial invitations along these lines: “Thank you for the invitation and I really support the idea of writing such a book, but unfortunately I cannot participate due to …”. Undeterred by such setbacks we gathered an initial group of authors willing to contribute and started the process. After about 6 months we had to realize that not all of the authors were holding up their end of the deal and we had to fi nd new contributors for the affected chapters. As you can see, we were successful, but the overall process from initiation to copy- editing was stretched out to almost 2 years. Any endeavor, and especially editing a book, is not possible without help and we would like to thank the chapter authors for their contributions. We further appreciate that some of the authors also pitched in with reviewing other chapters in the book. We would also like to extend our gratitude to our external reviewers: Mesut Muyan, Yusuf Tutar, Ekrem Varoğlu, Sreeparna Banerjee, Hasan Otu, and Gerhard Wilhelm Weber. Working together with professional editors at Methods in Molecular Biology was a great pleasure and especially David Casey and John Walker solved many a puzzling question. Dabburiya, Israel Malik Yousef Izmir , Turkey J ens Allmer vii Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi 1 Introduction to MicroRNAs in Biological Systems . . . . . . . . . . . . . . . . . . . . . 1 Ayse Elif Erson-Bensan 2 The Role of MicroRNAs in Biological Processes . . . . . . . . . . . . . . . . . . . . . . . 15 Kemal Ug˘ur Tüfekci, Ralph Leo Johan Meuwissen, and S¸ermin Genç 3 The Role of MicroRNAs in Human Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . 33 Kemal Ug˘ur Tüfekci, Meryem Gülfem Öner, Ralph Leo Johan Meuwissen, and S¸ermin Genç 4 Introduction to Bioinformatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 Tolga Can 5 MicroRNA and Noncoding RNA-Related Data Sources . . . . . . . . . . . . . . . . . 73 Patrizio Arrigo 6 High-Throughput Approaches for MicroRNA Expression Analysis . . . . . . . . . 91 Bala Gür Dedeog˘lu 7 Introduction to Machine Learning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 Yalin Başstanlar and Mustafa Özuysal 8 Introduction to Statistical Methods for MicroRNA Analysis . . . . . . . . . . . . . . 129 Gökmen Zararsiz and Erdal Co¸sgun 9 Computational and Bioinformatics Methods for MicroRNA Gene Prediction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Jens Allmer 10 Machine Learning Methods for MicroRNA Gene Prediction. . . . . . . . . . . . . . 177 Müşerref Duygu Saçar and Jens Allmer 11 Functional, Structural, and Sequence Studies of MicroRNA . . . . . . . . . . . . . . 189 Chanchal K. Mitra and Kalyani Korla 12 Computational Methods for MicroRNA Target Prediction . . . . . . . . . . . . . . . 207 Hamid Hamzeiy, Jens Allmer, and Malik Yousef 13 MicroRNA Target and Gene Validation in Viruses and Bacteria. . . . . . . . . . . . 223 Debora Baroni and Patrizio Arrigo 14 Gene Reporter Assay to Validate MicroRNA Targets in Drosophila S2 Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233 Bünyamin Akgül and Çag˘da¸s Gökta¸s 15 Computational Prediction of MicroRNA Function and Activity. . . . . . . . . . . . 243 Hasan Og˘ul 16 Analysis of MicroRNA Expression Using Machine Learning . . . . . . . . . . . . . . 257 ix