Proteomics and metabolomics: can they solve some mysteries of the newborn?

“Omics” (genomics, transcriptomics, proteomics and metabolomics) represent the complexity of biological systems which is strongly emerging in the most recent literature [1,2]. “Omics” are going to replace traditional laboratory methodologies (not sensitive or specific enough to diagnose a disease) thanks to their capacity to distinguish a single subject in normal conditions (phenome) and, in the case of disease (diseasome), with a simultaneous, and often noninvasive analysis of a large amount of data (the so-called “direct intelligence of data”) [3]. In particular, it is important not only the potential of genes but also their interactions with the environment, which bring the phenotype into being [4].

An integrated approach could be the answer to many of the unanswered questions in clinical medicine. For example proteomic approach has been used by our group to identify mechanisms involved in hypoxic brain injury in guinea pig brain synaptosomes. Voltage-dependent anion channel (VDAC) protein isoforms, selectively undergo hypoxia-induced tyrosine phosphorylation, suggesting that tyrosine phosphorylation may contribute to the modulation of VDAC protein function/conformation or interaction with other proteins in hypoxic conditions [5,6].

Wang-Sattler [7] using metabolite–protein network analysis in adult patients, identified seven type 2 diabetes-related genes that are associated with three impaired glucose tolerance-specific metabolites by multiple interactions with four enzymes. In particular three metabolites (glycine, lysophosphatidylcholine (LPC) (18:2) and acetylcarnitine) had significantly altered levels in impaired glucose tolerance individuals as compared to those with normal glucose tolerance.

The first consideration is that it is not necessary to study all the “Omics”, but it is enough, in a more simple and easier way, to perform metabolomics which summarizes the gene-environment interactions. The second consideration is that if some individual presents the alteration in the three metabolites he/she has not a probability to develop type 2 diabetes (epidemiologic medicine), then he/she will surely develop type 2 diabetes. These results may help developing novel strategies to prevent type 2 diabetes. If not, we could retard the development of the pathology or its complications. We cannot change our past, but we can try to ameliorate our future, for example by changing our eating habits and limiting or personalizing the use of drugs, avoiding pollution, thus modulating our life styles. Genetics is printed in ink and cannot be deleted, while epigenetics is written in pencil and can be modified [6]. Genetics proposes while epigenetics provides [7].

Proteomics is the global study of proteins in a biological system, tissue or bodily fluid. The potential of proteomics in the area of personalized pediatric medicine has been recently discussed since this is of particular clinical relevance [8], focusing for example on the application of proteomics to nutrition [9], nephrology [10] or neonatology with particular emphasis on diseases where oxidative stress plays a key pathophysiological role [7]. However, many obstacles must be surmounted before pediatric proteomics is optimally useful for clinicians.

Metabolomics consists of the quantitative analysis of a large number of low molecular mass metabolites involving substrates or products in metabolic pathways existing in all living systems. The fluids most frequently used in pediatrics and neonatology are urine, cord blood plasma, and also milk and stools have been studied. Each condition or disease presents a specific discriminating set of metabolites, which can be considered like a “bar code”.

Is there a metabolomic-based evidence in neonatology and pediatrics, today? Unfortunately, the answer is not. However the number of papers published in literature is constantly increasing. The latest papers are related to intrauterine growth restricted and small for gestational age neonates, prematurity, mode of delivery, hypoxic-ischemic encephalopathy, persistent ductus arteriosus, respiratory syndrome and surfactant therapy, cytomegalovirus infection, nephrouropathy, inborn errors of metabolism, twins, obesity, pharmametabolomics and nutrimetabolomics (including study of maternal milk and formula) [11--20]. The authors are performing studies together, especially on perinatal asphyxia, pediatric nephrology, metabolic syndrome. A specific field of interest is looking at “old” data (oxidative stress) [21–24] with “new” eyes (metabolomics), perinatal programming (“in my beginning is my end”). In this context relevant studies have very recently been published on system biology, epigenetics and aging [25–26].

It must be stressed that the complexity of biological systems is strongly emerging in the most recent literature and the market for metabolomic data analysis tools and software is increasing day by day. The global market for metabolomics in terms of revenue is estimated to be worth $343 million in 2012 and is expected to reach $1.5 billion by 2017, growing at a CAGR of 35% from 2012 to 2017 [27].

In the next few years we will witness a profound change in Medicine and healthcare, due to progress in technology and the ability to analyze large amounts of data from single patients. Proteomics and especially metabolomics will be major actors in the future scenarios of Medicine (Table 1) [28].

The evolution and interrelation of 4 technologies – nanotechnology, biotechnology, ICT (information and communication technology) and cognitive science is a sparking revolution in Medicine…, a revolution … far beyond the bounds of our imagination today [29].

Table 1. Differences between medicine of the past and of the future.

Medicine of the past	Medicine of the future
Epidemiologic	Individualized
Descriptive	Predictive
Reductionists	Holystic
Reactive	Prospective
Genetics-based	Epigenetics-based

From ref [28], with permission.

According to this, in the coming years, improved tools for the analysis of the metabolic profile (simplified like ‘dipsticks’ for urine) and its integration with the other ‘omics’ data, namely proteomics will probably move metabolomics beside the child, from top research to bedside. Urinary metabolomics will probably be ‘our world’, it will become one of the most used tools in Neonatology and Pediatrics and will be included in practical approach to neonatal management [30].

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.