Metallo-Cancer-Omics

Vojtěch Adam, Soňa Křížková, Zbyněk Heger, Ondřej Zítka and René Kizek


Recent advances in understanding the human genome have been made possible due to multidisciplinary cooperation between life sciences and technology. Genomics has succeeded in producing complete genomic DNA sequences of numerous species, but we are still some way from understanding differences between normal and pathological processes of cells and organisms [1]. Currently, attention is paid towards proteomics providing information about proteins localizations, structures and function, and most importantly, interaction with other proteins [2]. Recent progresses in high-throughput sample separation and mass spectrometry have impacted positively the proteomic characterization of proteins in systems biology [3]. Metalloproteins belong to the most diverse classes of protein, with intrinsic metal atoms providing a catalytic, regulatory and structure role essential to proteins function [4]. Transition metals such as copper, iron and zinc play important roles in life. Zn, the most abundant cellular transition metal, plays a vital role for functions of more than 300 enzymes, in DNA stabilization and in gene expression [5]. As some metals are crucial for body function, dyshomeostasis or deficiency of these elements can result in disease [6-8]. The Metallome is the distribution of inorganic species in cell. Metallomics and metalloproteomics are emerging fields addressing the role, uptake, transport and storage of the trace metals essential for life. Metallomics is defined as the analysis of the entirety of metal and metalloid species within a cell or tissue, whereas metalloproteomics focuses on exploration of the function of metals associated with proteins [9]. There are three main approaches being developed in metallomics and metalloproteomics: The first is and widely used is mass spectrometry, particularly electrospray ionisation mass spectrometry (ESI-MS) and inductively coupled plasma mass spectrometry connected with laser ablation (LA-ICP-MS). This connection allows us to see the lateral distribution of elements on the sample surface. These two techniques are ideal partners in comprehensive structural and functional characterization of metalloproteins. LA-ICP-MS has been extensively developed for elemental mapping in bio-imaging applications. [10, 11]. Second approach is high-throughput X-ray absorption spectroscopy (HT-XAS) to provide direct metal analysis of proteins and proteomic metals distribution in tissues and cells [12]. Third approach is computational bioinformatics analysis of the obtained results. Compared to genomics and proteomics, metallomics and metalloproteomics are relatively new fields that require the design and development of completely new analytical and computing approaches for dada analysis [13]. It has to be acknowledged that genomics and proteomics already have collected large amount of data that can be reused in metallomic and metalloproteomic studies to speed up advancement of these new disciplines. This is certainly a considerable advantage, but these data provide only a part of the complete picture – it has to be completed by additional numerous measurements of a different nature and processed by modern information technologies [4].

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