Digital and analogical reality in proteomics investigation

Abstract

Are protein functions continuous or discretized? Proteomics investigations are starting to address this non-trivial awesome question focusing upon determining the nature of biological molecular relationships. In the following editorial we present a number of experimental studies published in this themed Proteomics Issue demonstrating the development of a new analogical vision for the interpretation of genotype–phenotype relationships. New metrics and languages are evolving, which may complement the insufficiency based on a binary digital interpretation of biological phenomena, providing new tools for the interpretation of large scale-experimental studies.

Classical languages, as much as canonical experimental designs, are often based on an arithmetic binary logic. In fact, we tend to classify them with a positive and/or negative value, the deductive design we code in specific experimental investigations. The potential consequences of such an intellectual framework may frequently lead to classifications studies where a defined object is precisely framed into a specific function and role. This approach is the intellectual legacy of René Descartes who has provided a fundamental contribution in his masterpiece “Discours de la méthode pour bien conduire sa raison, et chercher la vérité dans les sciences”.¹ Such a vision has been particularly useful in providing a Linnaean molecular taxonomy on a number of fundamental physiological events. An analytical process bucketing every single molecular object with a defined event and/or function has lead to digitalization of many biological systems. This digital molecular vision of molecular biosystems has so far been the more explored, returning key results and information on a number of phenomena. The term digital is thus clearly associated with the independence of meaningful molecular effectors, which are considered as discrete molecular elements. However successful this vision has proved to be – single-gene genetic diseases are a classical example – many biological phenomena based on multi-factorial molecular determinants still remain unresolved. Indeed, today it is evident that many proteins exert different functions and exploit different physical and functional interactions, differentiated in space and time in connection with their environmental contest, as evidenced for haemoglobin before the -omics era, ref. 2 B. Giardina et al. Such an intellectual process is now directly providing new insight and new ideas to be functionally explored within the fundamental observation of natural phenomena.

The analogical nature of many molecular objects, in particular proteins, in being part of a large molecular biosystem is a fundamental concept in proteomics investigations. This themed issue on proteomic studies is providing a tangible demonstration of this vision. In fact, several published papers are addressing a multifactorial framework of distinct biological systems.

In this themed issue, a definition of a new metric system for the annotation of multi-labelled components in proteins is described in a theoretical paper from Chou (DOI:10.1039/c3mb25555g), which represents an important step towards setting up novel intellectual tools to explore the analogical nature of complex biosystems. Experimental evidences of a large inter-linked model of protein functions are given in a number of papers herein targeting different biological systems. The work of Vergara et al. (DOI: 10.1039/c2mb25401h) provided further novel insight into specific protein signatures associated with the epithelial-mesenchymal transition. Different biological functions, such as cell adhesion, migration, invasion, metabolism, survival and proliferation have been mapped and connected in a complex model. The results provide a pharmacological inhibition strategy, which may reverse the mesenchymal phenotype to an epithelial phenotype. Furthermore, the molecular integration strategy is extended in the study of Ciavardelli et al. (DOI: 10.1039/c3mb25594h), which proposed a combined approach to assess ion homeostasis and protein function relationships in a specific isogenic CFTR model system of cystic fibrosis. Importantly this model offers new possibilities for the interpretation of a specific disease phenotype arising from a single-gene mutation. The extension of this consideration to mutations in multiple protein-coding genes is brought into the light by the opinion paper from Matthias Gstaiger and Ruedi Aebersold (DOI: 10.1039/c3mb25583b) who are pinpointing the highly modular organization of the protein landscape arising from large-scale -omics experiments. The relationships between the genotype–phenotype are a fundamental topic for the development of large-scale international collaborative projects, in particular those related to the Human Proteome Project (HPP) initiatives. An example of this includes the consensus paper of the Italian HPP initiative based on Mitochondria, providing the hallmarks for both the Chromosome (C-HPP) and the Biology and Disease (B/D-HPP) programs.³ Clearly these concepts do not just uniquely reflect the Homo sapiens model, the original experimental paper from Alessio Soggiu et al. (DOI: 10.1039/c3mb25494a) casts this vision into the animal-production field addressing the molecular determinant of bull fertility by a multivariate investigation of the protein repertoire. The moonlighting roles of proteins in the control and development of minimal cellular models are discussed in the review paper from Fabian M. Commichau and colleagues (DOI: 10.1039/c3mb25595f) on a revision of the essential genes for the survival of Bacillus subtilis. They address some key issues in the continuous and discretized role of proteins in controlling a living organism.

In the end, we should mention the Italian Proteomics Association (www.ItPA.it), which has been promoting scientific discussion in this area of interest, and supported the development of this themed Proteomics Issue following the Viterbo ItPA Congress – EU-COST Action FA1002 meeting (June 2012).

References

1. Discours de la méthode pour bien conduire sa raison, et chercher la vérité dans les sciences; René Descartes (1637), http://www.gutenberg.org/files/13846/13846-h/13846-h.htm.
2. B. Giardina, I. Messana, R. Scatena and M. Castagnola, The multiple function of hemoglobin, Crit. Rev. Biochem. Mol. Biol., 1995, 30, 165–196.
3. A. Urbani and M. De Canio, et al., ‘The Mitochondrial Italian Human Proteome Project Initiative (mt-HPP)’, Mol. Biosyst 10.1039/C3MB70065H.

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