Computational Methods For Multi Omics Data Analysis In Cancer Precision Medicine

Cancer is a complex and heterogeneous disease often caused by different alterations. The development of human cancer is due to the accumulation of genetic and epigenetic modifications that could affect the structure and function of the genome. High-throughput methods (e.g., microarray and next-generation sequencing) can investigate a tumor at multiple levels: i) DNA with genome-wide association studies (GWAS), ii) epigenetic modifications such as DNA methylation, histone changes and microRNAs (miRNAs) iii) mRNA. The availability of public datasets from different multi-omics data has been growing rapidly and could facilitate better knowledge of the biological processes of cancer. Computational approaches are essential for the analysis of big data and the identification of potential biomarkers for early and differential diagnosis, and prognosis.

Cancer is the second most common cause of death worldwide and encompasses highly variable clinical and biological scenarios. Some of the current clinical challenges are (i) early diagnosis of the disease and (ii) precision medicine, which allows for treatments targeted to specific clinical cases. The ultimate goal is to optimize the clinical workflow by combining accurate diagnosis with the most suitable therapies. Toward this, large-scale machine learning research can define associations among clinical, imaging, and multi-omics studies, making it possible to provide reliable diagnostic and prognostic biomarkers for precision oncology. Such reliable computer-assisted methods (i.e., artificial intelligence) together with clinicians' unique knowledge can be used to properly handle typical issues in evaluation/quantification procedures (i.e., operator dependence and time-consuming tasks). These technical advances can significantly improve result repeatability in disease diagnosis and guide toward appropriate cancer care. Indeed, the need to apply machine learning and computational intelligence techniques has steadily increased to effectively perform image processing operations-such as segmentation, co-registration, classification, and dimensionality reduction-and multi-omics data integration.

Precision medicine holds great promise for the treatment of cancer and represents a unique opportunity for accelerated development and application of novel and repurposed therapeutic approaches. Current studies and clinical trials demonstrate the benefits of genomic profiling for patients whose cancer is driven by specific, targetable alterations. However, precision oncologists continue to be challenged by the widespread heterogeneity of cancer genomes and drug responses in designing personalized treatments. Chapters provide a comprehensive overview of the computational approaches, methods, and tools that enable precision oncology, as well as related biological concepts. Covered topics include genome sequencing, the architecture of a precision oncology workflow, and introduces cutting-edge research topics in the field of precision oncology. This book is intended for computational biologists, bioinformaticians, biostatisticians and computational pathologists working in precision oncology and related fields, including cancer genomics, systems biology, and immuno-oncology.

A hallmark of high-quality cancer care is the delivery of the right treatment to the right patient at the right time. Precision oncology therapies, which target specific genetic changes in a patient's cancer, are changing the nature of cancer treatment by allowing clinicians to select therapies that are most likely to benefit individual patients. In current clinical practice, oncologists are increasingly formulating cancer treatment plans using results from complex laboratory and imaging tests that characterize the molecular underpinnings of an individual patient's cancer. These molecular fingerprints can be quite complex and heterogeneous, even within a single patient. To enable these molecular tumor characterizations to effectively and safely inform cancer care, the cancer community is working to develop and validate multiparameter omics tests and imaging tests as well as software and computational methods for interpretation of the resulting datasets. To examine opportunities to improve cancer diagnosis and care in the new precision oncology era, the National Cancer Policy Forum developed a two-workshop series. The first workshop focused on patient access to expertise and technologies in oncologic imaging and pathology and was held in February 2018. The second workshop, conducted in collaboration with the Board on Mathematical Sciences and Analytics, was held in October 2018 to examine the use of multidimensional data derived from patients with cancer, and the computational methods that analyze these data to inform cancer treatment decisions. This publication summarizes the presentations and discussions from the second workshop.

The advancement of biomedical engineering has enabled the generation of multi-omics data by developing high-throughput technologies, such as next-generation sequencing, mass spectrometry, and microarrays. Large-scale data sets for multiple omics platforms, including genomics, transcriptomics, proteomics, and metabolomics, have become more accessible and cost-effective over time. Integrating multi-omics data has become increasingly important in many research fields, such as bioinformatics, genomics, and systems biology. This integration allows researchers to understand complex interactions between biological molecules and pathways. It enables us to comprehensively understand complex biological systems, leading to new insights into disease mechanisms, drug discovery, and personalized medicine. Still, integrating various heterogeneous data types into a single learning model also comes with challenges. In this regard, learning algorithms have been vital in analyzing and integrating these large-scale heterogeneous data sets into one learning model. This book overviews the latest multi-omics technologies, machine learning techniques for data integration, and multi-omics databases for validation. It covers different types of learning for supervised and unsupervised learning techniques, including standard classifiers, deep learning, tensor factorization, ensemble learning, and clustering, among others. The book categorizes different levels of integrations, ranging from early, middle, or late-stage among multi-view models. The underlying models target different objectives, such as knowledge discovery, pattern recognition, disease-related biomarkers, and validation tools for multi-omics data. Finally, the book emphasizes practical applications and case studies, making it an essential resource for researchers and practitioners looking to apply machine learning to their multi-omics data sets. The book covers data preprocessing, feature selection, and model evaluation, providing readers with a practical guide to implementing machine learning techniques on various multi-omics data sets.

This book concisely describes the role of omics in precision medicine for cancer therapies. It outlines our current understanding of cancer genomics, shares insights into the process of oncogenesis, and discusses emerging technologies and clinical applications of cancer genomics in prognosis and precision-medicine treatment strategies. It then elaborates on recent advances concerning transcriptomics and translational genomics in cancer diagnosis, clinical applications, and personalized medicine in oncology. Importantly, it also explains the importance of high-performance analytics, predictive modeling, and system biology in cancer research. Lastly, the book discusses current and potential future applications of pharmacogenomics in clinical cancer therapy and cancer drug development.

Praise for Computational Systems BiologyApproaches in Cancer Research: "Complex concepts are written clearly and with informative illustrations and useful links. The book is enjoyable to read yet provides sufficient depth to serve as a valuable resource for both students and faculty." — Trey Ideker, Professor of Medicine, UC Xan Diego, School of Medicine "This volume is attractive because it addresses important and timely topics for research and teaching on computational methods in cancer research. It covers a broad variety of approaches, exposes recent innovations in computational methods, and provides acces to source code and to dedicated interactive web sites." — Yves Moreau, Department of Electrical Engineering, SysBioSys Centre for Computational Systems Biology, University of Leuven With the availability of massive amounts of data in biology, the need for advanced computational tools and techniques is becoming increasingly important and key in understanding biology in disease and healthy states. This book focuses on computational systems biology approaches, with a particular lens on tackling one of the most challenging diseases - cancer. The book provides an important reference and teaching material in the field of computational biology in general and cancer systems biology in particular. The book presents a list of modern approaches in systems biology with application to cancer research and beyond. It is structured in a didactic form such that the idea of each approach can easily be grasped from the short text and self-explanatory figures. The coverage of topics is diverse: from pathway resources, through methods for data analysis and single data analysis to drug response predictors, classifiers and image analysis using machine learning and artificial intelligence approaches. Features Up to date using a wide range of approaches Applicationexample in each chapter Online resources with useful applications’