*2.1. Why Use the Broad Interpretation of the Term Epiproteome?*

Our concepts of how the molecular machinery in a cell operates have changed radically over the last three decades. One-dimensional models of static proteins acting alone to promote a particular enzymatic step have been superseded by an understanding that proteins typically act as parts of molecular nano-machines in complexes, and are dynamically controlled by a combination of their own intrinsic flexibility [4], their micro-environment, location and their interactions with their partners. We know that robust control of cellular processes needs to occur at multiple levels [5] that can include modifications of chromatin, transcription, post-transcription, translation and PTM. Epigenetic changes and their role in host plasticity have been widely discussed over the last decade [6,7], including their role in responding to challenges such as pathogens [8]. More recently epitranscriptomic changes have become a topic of renewed interest [9]. It is timely therefore to focus on the epiproteome and the key role that PTM could play in coordinated cellular response to pathogens and other stresses. There are of course thousands of papers referring to specific post-translational modifications or similar terms. Initially epiproteomics referred simply to changes in the specific proteome associated with DNA epigenetic changes [1]. And indeed it is still sometimes used in this way now [10]. Only recently have papers used the term to refer to the sum of all post-translational changes in all proteins or a subset such as the redox or cysteine epiproteome [2,11]. The term epiproteomics evokes a parallel with the temporal nature of epigenetics that is entirely appropriate, and perhaps even central, to the importance of the PTM level of control. Therefore below the term epiproteome is applied in a much more general way to any post-translational modification of any protein in any protein complex. PTM can lead to a large ensemble of forms of the components of the proteome existing in a dynamic state within a cell. Unfortunately, the research tools required to analyse PTM states properly are still expensive to run and hence our current picture of the dynamics of these states is inadequate. PTM alternative states

are however likely to be more significant than random noise and there are numerous individual cases where this is confirmed.
