Chapter 25

Phenomics

The ultimate goal, to which the study of genome and proteome lead (cf. Fig. 2.1), is

to understand phenotype, and phenomics is the science of the phenotype. ¹ Mainly,

it should be understood as the science of how to measure phenotype. In the case of

static attributes (e.g., eye colour) or uniformly increasing ones (e.g., bacterial cell size

under certain conditions) this is straightforward. In other cases, such as behaviour

(Sect. 25.3), it is not.

25.1

Enzyme Activity-Based Protein Profiling

Except for those few diseases that can be linked to disorders in a single gene, in

most cases genetic profile is a very poor predictor of susceptibility to succumbing

to disease. The transcriptome also has limitations, because it does not include post-

translational modifications of proteins, such as glycosylation, which can enormously

change properties. To gain insight into what abnormality might be the cause of a

disease, such as a metabolic disorder, it is best to directly measure the activities of key

enzymes. In effect this is proteomics, but proteomics is typically only concerned with

the identities and abundances of the protein repertoire. The activity-based approach

preferably uses small probes interacting with enzyme active sites to give an indication

of activity. ²

One area that has been quite exhaustively investigated from this perspective is

the organophosphate detoxification activity of paraoxonase (PON1), which depends

on the catalytic efficiency of hydrolysis of the enzyme substrate. Although there are

particular polymorphisms in the gene that change the catalytic activity of the enzyme,

1 Bilder et al. (2009).

2 Barglow and Cravatt (2007).

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J. Ramsden, Bioinformatics, Computational Biology,

https://doi.org/10.1007/978-3-030-45607-8_25

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