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2 K. Ning and Y. Li Fig. 1.1 The generalized definition of multi-omics. Large-scale acquisition of omics data from different molecular levels such as genome, transcriptome, proteome, epigenome, metabolome, microbiome, etc., and integrated analysis to achieve a deeper understanding of biological processes and molecular mechanisms include those data from bioimaging, biosensors, and even social networks (Antonelli et al. 2019; Sriram and Subrahmanian 2020; Loizou 2016). 1.1 The History of Omics The omics studies have quite a long history. Back in 1958, the first sequencing technique emerged, as Frederick Sanger has invented the protein sequencing methods, especially the amino acid sequence of insulin (Heather and Chain 2016). However, sequencing technology did not develop significantly during the next twenty to thirty years. DNA was originally extracted in 1869, it was not until more than a century later that the first genomes were sequenced, making genomics a relatively new field that truly began in 1970s. 1.1.1 1971–1910: Discovery of DNA In 1871, Friedrich Miescher published a paper identifying the presence of nuclein and associated proteins in the nucleus. This is what we now call DNA, which is the foundation of the field of genomics. Walter Sutton and Theodor Boveri discovered in 1904 that chromosomes appeared in pairs, with one inherited from each parent., which is known as the theory of chromosome inheritance. In 1910, Albert Kossel discovered the five nucleotide bases: adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U). 1 Introduction to Multi-Omics 3 1.1.2 1950–1968: Development of Knowledge about DNA Erwin Chargaff discovered the base pairing of adenosine, cytosine, guanine, and thymine nucleotides in 1950. He discovered that the concentrations of thymine and adenine or cytosine and guanine in DNA samples are always equal. As a result, he concluded that adenosine and thymine form a chromosome pair, while cytosine and guanine form a chromosome pair. In 1952, Alfred Hershey and Martha Chase proved through a series of experi- ments that it was DNA, not protein, that carried inherited genetic features. The following year, the double helix structure of DNA was discovered by James Watson and Francis Crick (Portin 2014). A research team led by Marshall Nirenberg and Har Gobind Khorana discovered what is now known as DNA “codons” in 1961

5 Contents 1 Introduction to Multi-Omics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Kang Ning and Yuxue Li Part I Omics Integration Techniques 2 Biomedical Applications: The Need for Multi-Omics . . . . . . . . . . . . . 13 Yuxue Li and Kang Ning 3 -Omics Technologies and Big Data . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Ansgar Poetsch and Yuxue Li 4 Multi-Omics Data Mining Techniques: Algorithms and Software . . . 5 Min Tang, Yi Liu, and Xun Gong Part II Applications of Multi-omics Analyses 5 Multi-Omics Data Analysis for Cancer Research: Colorectal Cancer, Liver Cancer and Lung Cancer . . . . . . . . . . . . . . . . . . . . . . 77 Hantao Zhang, Xun Gong, and Min Tang 6 Multi-Omics Data Analysis for Inflammation Disease Research: Correlation Analysis, Causal Analysis and Network Analysis . . . . . . 101 Maozhen Han, Na Zhang, Zhangjie Peng, Yujie Mao, Qianqian Yang, Yiyang Chen, Mengfei Ren, and Weihua Jia 7 Microbiome Data Analysis and Interpretation: Correlation Inference and Dynamic Pattern Discovery . . . . . . . . . . . . . . . . . . . . 119 Kang Ning and Yuxue Li ix x Contents 8 Current Progress of Bioinformatics for Human Health . . . . . . . . . . . 145 Jin Zhao, Shu Zhang, Shunyao Wu, Wenke Zhang, and Xiaoquan Su Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167

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