Cytomics in the realm of systems biology

Abstract

CONVERGENCE OF SYSTEMS BIOLOGYAND CYTOMICS The current focus of systems biology is on the reverse engineering of networks to model gene regulatory or protein-protein interactions and the extraction of basic principles of biological organization. The ability of in silico representations to predict of how a system being in a particular state may react and adjust to perturbations has made systems biology an attractive component for basic research, drug development, and predictive medicine. However, computational systems biology is less experienced in implementing spatiotemporal properties of cells and multicellular architectures, and attempts to integrate and interconnect various levels of biological organization, such as genes, proteins, cells, and tissues, are a rare occurrence.As opinions about the nature of Cytomics as a discipline arise, and activities and projects evolve, more specific definitions may become available. At this point it should be noted that even systems biology, which already has a track record of successful research activities, still experiences debates of what it is or should be. Cytomics is currently centered on high-throughput, multiparametric imaging in conjunction with machine vision to quantify cellular morphologies and properties like protein activities, with the underlying notion of a hypothesis-free approach. It aims to provide comprehensive, accurate, unbiased and systematic data, features that have been defined as the cornerstones for measurement technologies in systems biology (1). Applications for a systematic profiling of different cells, such as all cell types in the human body, have been suggested (2). Systematic screening projects will enable us to populate a rather sparse data area above the level of the proteome.Cytomics appreciates single cell properties, which is of great value since averaging can seriously limit systems biology approaches, such as network analyses. The example recently demonstrated applied reverse engineering in T-cells, using multiparameter flow cytometry and Baysian statistics (3). Targeting multiple protein activators and inhibitors allowed simultaneous monitoring of the phosphorylation status of many protein species. As each pathway in each cell is in a particular status of activation, signaling networks can be more accurately revealed by taking multiparameter snapshots of many cells when compared to procedures that rely on averaged information out of cell lysates. SPACE IN SYSTEMS BIOLOGYCytomics introduces something new that systems biology has not thoroughly considered yet: The ability to image makes quantitative spatial (and time resolved) measures of protein distributions and local concentrations, patterns related to organelles, and properties of transport phenomena between intracellular compartments available. Related projects include single cell-based response evaluation to drug treatment (4), pattern recognition of localized protein distributions that improve currently available ontologies (5), as well as analysis of changes of subcellular ph...

Aneuploidy and DNA Replication in the Normal Human Brain and Alzheimer's Disease

“…The use of cytometry together with molecular biology methods is a promising approach to studying mechanisms at molecular and cellular levels (Darzynkiewicz et al, 2001). Such single-cell analysis with different methods reflects the concept of cytomics and will forward our understanding of the molecular architecture and functionality of neuronal systems (Valet et al, 2004;Kriete, 2005). As in our studies the DNA content of single neurons determined by SBC is far better correlated to CISH than is the qPCR measurement, we conclude that SBC is a very reliable technique for future studies on the single cell DNA content in tissue sections.…”

Apoptosis of circulating lymphocytes during pediatric cardiac surgery

“…The multicolor analysis of biological specimens has become increasingly important in various fields of biology in particular due to the emerging new fields of high-content and high-throughput single cell analysis for systems biology 1-6 and cytomics 7,8 . There is a constant need for clinical diagnostic systems that enable to predict disease course which in turn would enable for preventative medicine.…”

Hyperchromatic laser scanning cytometry

“…Since our view of cellular systems gets more complex, the characterization of cell subsets makes the use of more parameters necessary and even unavoidable 8,9,10 . Therefore, highly multiplexed characterization of cells on the single cell level is a pivotal technology for single cell genomics, protemics and cytomics 1,2,4,6,7,[11][12][13] . With the increased number of measurable characteristics of a cell in addition with its morphological evaluation SBC multiplexed cell analysis is a powerful analytical and diagnostic tool.…”