Cytopostgenomics: What is it and how does it work?

Abstract

In 2018, a special hot-topic issue of Current Genomics covering numerous important aspects of molecular cytogenetics and cytogenomics in the postgenomic era was published (Current Genomics, Volume 12, Issue/Number 3, Pages: 157-246) [1]. As a result, the theoretical basis for a new emerging field of cytogenomic research tentatively termed as "cyto(post)genomics" was provided. Tragically, the passing away of my co-editor and closest colleague, Professor Yuri B. Yurov [2], hindered immediate attempts to delineate the area of "cytopostgenomics". Accordingly, I take the opportunity to contribute a Perspectives in Genomics article to re-introduce cytopostgenomics in remembrance of Professor Yuri B. Yurov, the brilliant researcher of chromosomes and cellular genomes.More than a decade ago, cytogenomics (molecular cytogenomics) was introduced to define a body of research in human genomics (genetics) focused on genomic variations and architecture at microscopic/submicroscopic level and at molecular resolutions [3]. Later, it expanded to include a wide spectrum of applications of whole-genome Copy Number Variation (CNV) analysis (cytogenomic analysis or analysis of cytogenomic variations) in diagnostic research [4,5].Currently, cytogenomics (in its widest sense) seems to encompass almost all areas of chromosome biology addressed in the genomic context [1,[3][4][5]. Using postgenomic approaches to chromosomal variations and instability, a number of discoveries in chromosome biology and re-evaluations of current concepts in genomics have been made [6]. In addition to analysis of submicroscopic genomic variations for the association with specific phenotypes [3][4][5], cytogenomics has shed light on genome behavior (i.e. genome instability) throughout ontogeny [7] including more specific genomic changes (accumulation of somatic genomic variations) associated with normal and abnormal aging [8,9]. Moreover, genome-environment interactions highlighting normal and pathogenic responses of cellular genomes to environmental stimuli, which partially underlie somatic mutagenesis, have been highlighted [10]. The variable effects of the genomic variations have resulted in the interpretational problem of cytogenomic data [3][4][5][6]11]. Fortunately, postgenomic research has provided numerous bioinformatic opportunities to solve the problem by proposing a variety of algorithms for processing molecular cytogenetic and (cyto)genomic data [11,12]. As a result, actual cytogenomic research cannot be appropriately performed without corresponding postgenomic analysis (i.e. systems biology approaches and pathway-based classification) [12]. Furthermore, genome analysis for specific medical tasks (e.g. pediatric research) has already benefited from the application of postgenomic approaches to processing genomic data [13]. More precisely, pathway-based views on human diseases have heavily influenced our understanding of the disease etiology [14]. Finally, postgenomic approaches to processing cytogenomic data are able to deliver effective therapeuti...

Ontogenetic and Pathogenetic Views on Somatic Chromosomal Mosaicism

“…It is to note that molecular cytogenetic methodology for visualizing interphase chromosomes cannot be completely substituted by single-cell whole genome scanning techniques [241]. Although post-genomic technologies allow single-cell genomic analysis at the highest resolution possible, uncovering chromosomal intercellular heterogeneity still requires visualization of chromosomal loci by cytogenetic karyotyping and FISH-based methods [234,248,249].…”

“…Recently, we have proposed a workflow for studies of mosaic aneuploidy and chromosome instability for uncovering molecular/cellular disease mechanisms in the post-genomic era (i.e., cytopostgenomic studies). The term cytopostgenomics have been coined to cover an emerging bioscience field dedicated to postgenomic analysis focused on causes and consequences of chromosomal variations and architecture [248]. According these considerations, high-resolution whole genome scanning technologies and post-genomic bioinformatic approaches (specifically developed for molecular cytogenetics, i.e., [149,165,167,180]) are to be used to reveal molecular causes of chromosomal heterogeneity identified by cytogenetic and molecular cytogenetic techniques [241,248,249].…”

Systems Cytogenomics: Are We Ready Yet?

“…Systems genomics is an important part of current bioscience, providing evidence-based theoretical and empirical discoveries [ 1 , 2 ]. However, systems genomics approaches are rarely used in cytogenetic/cytogenomic research ( i.e ., genome analysis at chromosomal and subchromosomal levels) regardless of the proven efficiency and applicability [ 3 ]. In the post-genomic era, data analysis by systems biology (bioinformatic) techniques has become a key contributor to the success of a study dedicated to genome biology/ medicine [ 4 , 5 ].…”

Dynamic nature of somatic chromosomal mosaicism, genetic-environmental interactions and therapeutic opportunities in disease and aging

“…Chromosome-oriented postgenomic studies are able to provide new understanding how genomic variations produce the phenotype at saupramolecular or nuclear level and what can be done to diminish the effect of causative mutations. The latter may be achieved by either correcting the pathways altered by chromosome abnormalities/instability or decreasing the number of cells carrying the mutations [81][82][83][84]. Since cancers are one of the most intriguing models for somatic mutagenesis, a number of the theoretical and empirical (oncocytogenetic) observations may contribute to our hypothesis.…”