CYTOMICS : MANAGING BIOCOMPLEXITY IN DRUG DEVELOPMENT , CLINICAL DIAGNOSTICS , AND CLINICAL MEDICINE

Dealing with the overwhelming volume and complexity of data is one of the major challenges in translating our increasingly sophisticated knowledge of biology into useful information for clinical medicine. Biocomplexity in organisms arises from a combination of the diversity of genotypes among individuals and the variable exposure histories to environmental influences throughout life. Conventional reductionistic science cannot explain the behaviour of complex biological systems made up of networks that have scale-free, or clustered, architecture, and that manifest emergent properties. Yet, diseases are a consequence of aberrant activity of a subcomponent, or module, of a biological network. Thus, a thorough understanding of most diseases requires a more integrated, holistic approach to capture the complex networks established by the interacting components, reflecting genetic and exposure influences. Cytomics, the science of analysis at the cellular level, objectively accounts for functional phenotypes in the context of the entire organism. Furthermore, the cytomics top-down approach of data analysis does not depend on prior knowledge of disease mechanisms, thus significantly simplifying the exploration of organismal biocomplexity and shortening the path for applications in drug development, clinical diagnostics, and clinical medicine. Introduction This paper provides an introduction to cytomics and its applications through a review of the literature, focusing on genetics, genomics, and other ‘omics’. It also explains certain terminology at the beginning of the paper so that readers who are new to this area can benefit from the paper without having to consult other resources. A glossary is provided as Table 1. A Primer of the ‘Omics’ It is now 60 years since Watson and Crick proposed the structure of deoxyribonucleic acid (DNA), and others from the Cavendish laboratories at the University of Cambridge published complementary papers on this topic. The last sentence of Watson and Crick’s paper (composed by Crick) is one of the most beautifully understated scientific comments of all time: “It has not escaped our notice that the specific [base] pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” (See the entry “Bases” in Table 1.) There is nothing understated, however, about the veracity of their postulate and the current explosion of biological information that stands on its shoulders, particularly information made publicly available from the Human Genome Project. Genetics is the science that examines how traits are passed from one generation to the next.