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Precision Medicine involves an attempt to orchestrate the treatment approaches taken on a medical basis with respect to the condition of a particular patient. This should not be confused with the term “Personalized Medicine”, which implies a medical protocol adopted for a specific patent. In contrast, Precision Medicine is not so selective in that it involves treatment of a sub-population of patents that display certain medical features. The technology attracted significant attention in the world of medicine as a result of the Precision Medicine Initiative introduced by US President Barack Obama is his 2015 State of the Union address to Congress.

The main purposes of Precision Medicine lay in the potential ability of members of the medical community to actually prevent disease in the first place, follow disease progression more efficiently, tailor drug treatment effectively and enhance detection of disease, among a number of advantages. It is this last issue which is the main subject of this text in various forms. A key element of disease detection, for example, is the assay of molecular and cellular biomarkers. This technology is critical in the diagnosis and monitoring of a specific medical condition with respect to initial detection, progression and effect of drug treatment. A look at the relevant content of the various chapters follows.

The monograph is divided into four distinct sections, namely the topics of biomarkers, sequencing methods, ancillary techniques such as mass spectrometry, and clinical applications. The first deals extensively with a number of aspects of biomarker biology referred to above. Chapter 1 discusses micro RNA (miRNA) in terms of its relevance as a biomarker for diagnosis, prognosis and disease monitoring. These molecules, found in plants, animals and some viruses, consist of 20 or nucleotides that base pair with complementary sequences within mRNA molecules. They are frequently dysregulated during cancer initiation, development and metastasis, and are present in clinical specimens such as blood, saliva, urine and feces. Accordingly, their presence is an attractive biomarker for cancer and other diseases. The following chapter deals with the potential of extracellular vesicles (EVs) as biomarkers. These species are lipid bilayer-delimited particles that are mostly of dimension in the range 20–200 nm. They are thought to be involved in intercellular communication in processes such as the immune response. Importantly, they have been associated with the onset and progression of a multitude of human diseases; hence the current widespread interest in their detection as biomarkers. Chapter 3 evaluates the role that the science of proteomics can play in Precision Medicine. This topic, which has witnessed much evolution over a number of years, involves the study of the biochemistry, via cellular expression analyses, of both proteins and peptides. In this case, the emphasis is on the employment of separation-based mass spectrometry of proteins and peptides in not only biomarker detection, but also in therapeutics and diagnosis. The final two chapters in this section discuss the use of computation in Precision Medicine. In the first of these, neoantigens, which are antigens that have not been previously recognized by the immune system, and that can arise from altered tumor proteins formed as a result of tumor mutations or from viral proteins, are dealt with in the context of Precision Oncology. This area is especially important in terms of progress via predictive efforts with respect to immunotherapy. Finally, in the next highly related consideration, the topic of the use of big data analysis with regard to the genome, epigenome and transcriptome is introduced with, again, an emphasis on the response of these entities to therapy.

The five chapters in the next section concentrate on sequencing methods, especially as this area applies to detection of tumor cell mutations. Chapter 6 discusses the detection of disease-associated mutations and biomarkers using next-generation sequencing. It covers topics in detection of genomic mutations in protein coding regions and non-coding regulatory elements, detection of circulating tumor DNA, and studies of human and microbiome interactions, as well as applications of bioinformatics in biomarker detection and identification. In the next chapter, a state-of-the-art single-molecule, nucleic-acid-sequencing platform based on protein nanopores, which are embedded into a synthetic membrane, is considered. This technology allows the sequencing of up to 2 million bases and in this discussion the application of the approach to the detection of tumor mutations of various types is evaluated. Chapter 8 provides an appraisal of the issues and analytical challenges involved in the design of next-generation sequencing-based assays and their applications in Precision Medicine. Translating detection methods from the research setting into clinical application must address a broad range of challenges, including the development of standardized technologies and protocols in wet lab processing, sequencing, bioinformatics, big data and interpretation, and validated in population-based cohort studies and clinical trials. Chapter 9 deals specifically with single-cell sequencing of circulating tumor cells. These cells are shed from primary tumors in addition to metastatic lesions and are, therefore, present in the blood and lymphatic circulatory systems. Sequencing of nucleic acids in these cells can potentially increase the understanding of cancer-critical genetic alterations, the mechanism of metastasis and intratumor heterogeneity. This chapter also includes a look at the detection of mutations with reference to cancer characterization.

The next section of the text presents a set of novel methods that have been introduced in order to detect species within the format of Precision Medicine. The first chapter here returns to the science of proteomics through a treatment of the use of mass spectrometry for detection of processes involving proteins. Initially the discussion centers on the technique itself in terms of data-directed analysis (DDA) and data-independent acquisition (DIA). The former method involves a fixed number of precursor ions being selected and analyzed by tandem mass spectrometry, whereas in the latter approach, using the same instrument, the sequential isolation and fragmentation of ranges of ions is conducted. The chapter then proceeds to the topics of mass spectral profiling of protein expression, detection of protein-based biomarkers and the use of the technique in phosphoproteomics and kinomics. Chapter 11 considers the employment of immunoassays in Precision Medicine. This technology, which involves interaction of an antibody with a target (antigenic) species, will be familiar to clinical biochemists that use ELISA-based methods. Following a look at the different types of immunoassay approaches that are available, the chapter proceeds to examine detection strategies based on cytochemistry, histochemistry, electrochemistry and liposomes. Chapter 12 examines droplet technology, which is associated with generation by microfluidic devices on the scale of picoliters to nanoliters. The droplets act as individual microreactors and facilitate high-throughput and quantitative analysis, thus providing an attractive platform for the analysis of biomolecules or single cells in Precision Medicine. This type of device can also be used to manipulate droplets via mixing, sorting, merging, splitting and trapping. A compendium of employment of this technology in nucleic acid detection and characterization, liquid biopsy of tumor cells and exosomes, and drug screening follows. The final chapter in this section looks at the potential role of point-of-care testing (POCT) in Precision Medicine. This technology is concerned with medical diagnostic assays at or close to the point of patient care, often involving the doctor's office or hospital bedside. In this case, the chapter includes the use of nanoparticles, especially those composed of gold, in various forms of amplification of nucleic assays. Enzyme mimetic approaches for analogous nucleic acid detection are also discussed.

The last section of the text details a couple of clinical applications in the world of Precision Medicine. In the first chapter, the emphasis is on cell- and immune-based therapies. The thrust of this category of therapy involves the use of agents that harness the capabilities of the natural immune system in order to ameliorate the effects, for example, of tumor cells. The chapter introduces such factors as cytokines, e.g. interferon-based entities, that can cause cell lysis. The discussion also includes a description of checkpoint inhibitors which disrupt the signals of cancer cells, exposing them to the T-cells for attack. The chapter then proceeds to a highly detailed consideration of cell therapies which rely on allogeneic or autologous immune cells being harvested from patients and modified ex vivo and reinfused into patients as “living drugs.” The discussion concludes with a description of the combination of the two approaches outlined above. The final chapter in the text deals with the emerging science of Precision Oncology, which is defined by the same concept as specified in the subject text, but the medical strategy is more targeted towards treatment of cancer in patients. The chapter opens with a review of diagnostic approaches in the field, which includes cell and molecular profiling, transcriptomics, epigenetics and various sequencing technologies. This is followed by an appraisal of databases, treatment protocols and clinical aspects in Precision Oncology.

Finally, we would like to express our deep appreciation to all the authors of the book in contributing their knowledge and sharing their experience in the state-of-the art science and technology, especially during this period of COVID-19 pandemics, which further highlight the importance of detection science in disease prevention and diagnosis. Mengsu would like to thank the past and present members of his research group at City University of Hong Kong, and Mike would like to thank the Thompson Biosensors Group at the University of Toronto for their many valued research contributions and unfailing support. We also wish to thank Dr Xiaoyu Zhou of the City University of Hong Kong, and the Royal Society of Chemistry for their dedicated assistance in the preparation of various components of the manuscripts.

Michael Thompson

Mengsu Yang

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