Multi Omic Data Integration In Oncology

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Tutorial chapters by leaders in the field introduce state-of-the-art methods to handle information integration problems of omics data.

Stable, predictive biomarkers and interpretable disease signatures are seen as a significant step towards personalized medicine. In this perspective, integration of multi-omic data coming from genomics, transcriptomics, glycomics, proteomics, metabolomics is a powerful strategy to reconstruct and analyse complex multi-dimensional interactions, enabling deeper mechanistic and medical insight. At the same time, there is a rising concern that much of such different omic data –although often publicly and freely available- lie in databases and repositories underutilised or not used at all. Issues coming from lack of standardisation and shared biological identities are also well-known. From these considerations, a novel, pressing request arises from the life sciences to design methodologies and approaches that allow for these data to be interpreted as a whole, i.e. as intertwined molecular signatures containing genes, proteins, mRNAs and miRNAs, able to capture inter-layers connections and complexity. Papers discuss data integration approaches and methods of several types and extents, their application in understanding the pathogenesis of specific diseases or in identifying candidate biomarkers to exploit the full benefit of multi-omic datasets and their intrinsic information content. Topics of interest include, but are not limited to: • Methods for the integration of layered data, including, but not limited to, genomics, transcriptomics, glycomics, proteomics, metabolomics; • Application of multi-omic data integration approaches for diagnostic biomarker discovery in any field of the life sciences; • Innovative approaches for the analysis and the visualization of multi-omic datasets; • Methods and applications for systematic measurements from single/undivided samples (comprising genomic, transcriptomic, proteomic, metabolomic measurements, among others); • Multi-scale approaches for integrated dynamic modelling and simulation; • Implementation of applications, computational resources and repositories devoted to data integration including, but not limited to, data warehousing, database federation, semantic integration, service-oriented and/or wiki integration; • Issues related to the definition and implementation of standards, shared identities and semantics, with particular focus on the integration problem. Research papers, reviews and short communications on all topics related to the above issues were welcomed.

Computational Genomics with R provides a starting point for beginners in genomic data analysis and also guides more advanced practitioners to sophisticated data analysis techniques in genomics. The book covers topics from R programming, to machine learning and statistics, to the latest genomic data analysis techniques. The text provides accessible information and explanations, always with the genomics context in the background. This also contains practical and well-documented examples in R so readers can analyze their data by simply reusing the code presented. As the field of computational genomics is interdisciplinary, it requires different starting points for people with different backgrounds. For example, a biologist might skip sections on basic genome biology and start with R programming, whereas a computer scientist might want to start with genome biology. After reading: You will have the basics of R and be able to dive right into specialized uses of R for computational genomics such as using Bioconductor packages. You will be familiar with statistics, supervised and unsupervised learning techniques that are important in data modeling, and exploratory analysis of high-dimensional data. You will understand genomic intervals and operations on them that are used for tasks such as aligned read counting and genomic feature annotation. You will know the basics of processing and quality checking high-throughput sequencing data. You will be able to do sequence analysis, such as calculating GC content for parts of a genome or finding transcription factor binding sites. You will know about visualization techniques used in genomics, such as heatmaps, meta-gene plots, and genomic track visualization. You will be familiar with analysis of different high-throughput sequencing data sets, such as RNA-seq, ChIP-seq, and BS-seq. You will know basic techniques for integrating and interpreting multi-omics datasets. Altuna Akalin is a group leader and head of the Bioinformatics and Omics Data Science Platform at the Berlin Institute of Medical Systems Biology, Max Delbrück Center, Berlin. He has been developing computational methods for analyzing and integrating large-scale genomics data sets since 2002. He has published an extensive body of work in this area. The framework for this book grew out of the yearly computational genomics courses he has been organizing and teaching since 2015.

The occurrence of 5-methylcytosine in DNA was first described in 1948 by Hotchkiss (see first chapter). Recognition of its possible physiologi cal role in eucaryotes was first suggested in 1964 by Srinivasan and Borek (see first chapter). Since then work in a great many laboratories has established both the ubiquity of 5-methylcytosine and the catholicity of its possible regulatory function. The explosive increase in the number of publications dealing with DNA methylation attests to its importance and makes it impossible to write a comprehensive coverage of the literature within the scope of a general review. Since the publication of the 3 most recent books dealing with the subject (DNA methylation by Razin A. , Cedar H. and Riggs A. D. , 1984 Springer Verlag; Molecular Biology of DNA methylation by Adams R. L. P. and Burdon R. H. , 1985 Springer Verlag; Nucleic Acids Methylation, UCLA Symposium suppl. 128, 1989) considerable progress both in the techniques and results has been made in the field of DNA methylation. Thus we asked several authors to write chapters dealing with aspects of DNA methyla tion in which they are experts. This book should be most useful for students, teachers as well as researchers in the field of differentiation and gene regulation. We are most grateful to all our colleagues who were willing to spend much time and effort on the publication of this book. We also want to express our gratitude to Yan Chim Jost for her help in preparing this book.

This book is the first overview on Deep Learning (DL) for biomedical data analysis. It surveys the most recent techniques and approaches in this field, with both a broad coverage and enough depth to be of practical use to working professionals. This book offers enough fundamental and technical information on these techniques, approaches and the related problems without overcrowding the reader's head. It presents the results of the latest investigations in the field of DL for biomedical data analysis. The techniques and approaches presented in this book deal with the most important and/or the newest topics encountered in this field. They combine fundamental theory of Artificial Intelligence (AI), Machine Learning (ML) and DL with practical applications in Biology and Medicine. Certainly, the list of topics covered in this book is not exhaustive but these topics will shed light on the implications of the presented techniques and approaches on other topics in biomedical data analysis. The book finds a balance between theoretical and practical coverage of a wide range of issues in the field of biomedical data analysis, thanks to DL. The few published books on DL for biomedical data analysis either focus on specific topics or lack technical depth. The chapters presented in this book were selected for quality and relevance. The book also presents experiments that provide qualitative and quantitative overviews in the field of biomedical data analysis. The reader will require some familiarity with AI, ML and DL and will learn about techniques and approaches that deal with the most important and/or the newest topics encountered in the field of DL for biomedical data analysis. He/she will discover both the fundamentals behind DL techniques and approaches, and their applications on biomedical data. This book can also serve as a reference book for graduate courses in Bioinformatics, AI, ML and DL. The book aims not only at professional researchers and practitioners but also graduate students, senior undergraduate students and young researchers. This book will certainly show the way to new techniques and approaches to make new discoveries.

Large biological data, which are often noisy and high-dimensional, have become increasingly prevalent in biology and medicine. There is a real need for good training in statistics, from data exploration through to analysis and interpretation. This book provides an overview of statistical and dimension reduction methods for high-throughput biological data, with a specific focus on data integration. It starts with some biological background, key concepts underlying the multivariate methods, and then covers an array of methods implemented using the mixOmics package in R. Features: Provides a broad and accessible overview of methods for multi-omics data integration Covers a wide range of multivariate methods, each designed to answer specific biological questions Includes comprehensive visualisation techniques to aid in data interpretation Includes many worked examples and case studies using real data Includes reproducible R code for each multivariate method, using the mixOmics package The book is suitable for researchers from a wide range of scientific disciplines wishing to apply these methods to obtain new and deeper insights into biological mechanisms and biomedical problems. The suite of tools introduced in this book will enable students and scientists to work at the interface between, and provide critical collaborative expertise to, biologists, bioinformaticians, statisticians and clinicians.

This book encapsulates recent applications of CI methods in the field of computational oncology, especially cancer diagnosis, prognosis, and its optimized therapeutics. The cancer has been known as a heterogeneous disease categorized in several different subtypes. According to WHO’s recent report, cancer is a leading cause of death worldwide, accounting for over 10 million deaths in the year 2020. Therefore, its early diagnosis, prognosis, and classification to a subtype have become necessary as it facilitates the subsequent clinical management and therapeutics plan. Computational intelligence (CI) methods, including artificial neural networks (ANNs), fuzzy logic, evolutionary computations, various machine learning and deep learning, and nature-inspired algorithms, have been widely utilized in various aspects of oncology research, viz. diagnosis, prognosis, therapeutics, and optimized clinical management. Appreciable progress has been made toward the understanding the hallmarks of cancer development, progression, and its effective therapeutics. However, notwithstanding the extrinsic and intrinsic factors which lead to drastic increment in incidence cases, the detection, diagnosis, prognosis, and therapeutics remain an apex challenge for the medical fraternity. With the advent in CI-based approaches, including nature-inspired techniques, and availability of clinical data from various high-throughput experiments, medical consultants, researchers, and oncologists have seen a hope to devise and employ CI in various aspects of oncology. The main aim of the book is to occupy state-of-the-art applications of CI methods which have been derived from core computer sciences to back medical oncology. This edited book covers artificial neural networks, fuzzy logic and fuzzy inference systems, evolutionary algorithms, various nature-inspired algorithms, and hybrid intelligent systems which are widely appreciated for the diagnosis, prognosis, and optimization of therapeutics of various cancers. Besides, this book also covers multi-omics exploration, gene expression analysis, gene signature identification of cancers, genomic characterization of tumors, anti-cancer drug design and discovery, drug response prediction by means of CI, and applications of IoT, IoMT, and blockchain technology in cancer research.