| Literature DB >> 28725471 |
Marija Cvijovic1, Thomas Höfer2, Jure Aćimović3, Lilia Alberghina4, Eivind Almaas5, Daniela Besozzi6, Anders Blomberg7, Till Bretschneider8, Marta Cascante9, Olivier Collin10, Pedro de Atauri9, Cornelia Depner2, Robert Dickinson11, Maciej Dobrzynski12, Christian Fleck13, Jordi Garcia-Ojalvo14, Didier Gonze15, Jens Hahn16, Heide Marie Hess17, Susanne Hollmann18, Marcus Krantz16, Ursula Kummer19, Torbjörn Lundh1, Gifta Martial20, Vítor Martins Dos Santos21, Angela Mauer-Oberthür20, Babette Regierer18, Barbara Skene11, Egils Stalidzans22, Jörg Stelling23, Bas Teusink24, Christopher T Workman25, Stefan Hohmann26.
Abstract
Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological function by employing experimental data, mathematical models and computational simulations. As Systems Biology is inherently multidisciplinary, education within this field meets numerous hurdles including departmental barriers, availability of all required expertise locally, appropriate teaching material and example curricula. As university education at the Bachelor's level is traditionally built upon disciplinary degrees, we believe that the most effective way to implement education in Systems Biology would be at the Master's level, as it offers a more flexible framework. Our team of experts and active performers of Systems Biology education suggest here (i) a definition of the skills that students should acquire within a Master's programme in Systems Biology, (ii) a possible basic educational curriculum with flexibility to adjust to different application areas and local research strengths, (iii) a description of possible career paths for students who undergo such an education, (iv) conditions that should improve the recruitment of students to such programmes and (v) mechanisms for collaboration and excellence spreading among education professionals. With the growing interest of industry in applying Systems Biology approaches in their fields, a concerted action between academia and industry is needed to build this expertise. Here we present a reflection of the European situation and expertise, where most of the challenges we discuss are universal, anticipating that our suggestions will be useful internationally. We believe that one of the overriding goals of any Systems Biology education should be a student's ability to phrase and communicate research questions in such a manner that they can be solved by the integration of experiments and modelling, as well as to communicate and collaborate productively across different experimental and theoretical disciplines in research and development.Entities:
Year: 2016 PMID: 28725471 PMCID: PMC5516850 DOI: 10.1038/npjsba.2016.11
Source DB: PubMed Journal: NPJ Syst Biol Appl ISSN: 2056-7189
Suggested basic core areas for Systems Biology education
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| Linear algebra—as relevant for stoichiometric modelling, genome-scale metabolic reconstructions and models; stability analysis—as relevant for stability of genetic circuits |
| Nonlinear dynamics—as relevant for signalling cascades, kinetic metabolic models, pattern formation, enzyme dynamics, cell differentiation and cellular decision-making |
| Stochastic modelling—as relevant for gene expression circuits, cell motility, ion channels, protein–protein interaction, diffusion and signal transduction pathways |
| Spatial modelling—as relevant for morphogenesis, cell communication, tissue formation, crowding, biofilms |
| Control theory—as relevant for design and analysis of metabolic pathways, gene expression circuits, pharmacokinetics and pharmacodynamics |
| Discrete and logic models—as relevant for genetic networks, signalling networks and cellular differentiation |
| Complex network analysis—as relevant for metabolic networks, protein–protein interaction networks, gene–disease networks |
| Optimisation—as relevant for metabolic engineering, genome-scale metabolic models, parameter estimation in signal transduction networks and reverse engineering |
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| Metabolic networks—as relevant for physiology, human diseases and metabolic engineering; fluxes, kinetics, rates and stoichiometry |
| Signalling networks—as relevant for information processing and engineering of cells and organisms; dynamics, feedbacks and adaptation |
| Gene regulation networks—as relevant for cellular decision making and differentiation, bi- and multistability phenomena as well as circuit design in Synthetic Biology |
| Cell and population networks—as relevant for development, pattern formation, disease (especially cancer), infection and ecology; cell variability phenomena |
| Genetic networks—as relevant for multifactorial traits and diseases, epistasis, as well as genome-wide association studies and meta-analysis thereof |
| Protein (and other types of) interaction networks—as relevant for complex inference and functional modules |
| Oscillatory processes—as relevant for cell cycle, circadian rhythms, metabolic oscillations and other processes where timing regulates states of functional activity/inactivity |
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| Programming: e.g., Matlab or Mathematica, Python, Perl, Java, R, C and C++ |
| Tools for genome-scale metabolic models, kinetic modelling (stochastic and deterministic), network analysis: e.g., Copasi, Cytoscape, OptFlux, XPP-Auto and COBRA |
| Standards: e.g., SBML, SBGN and MIRIAM |
| Methods and software tools for biological data visualisation |
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| Fundamentals of DNA, RNA and protein sequence analysis |
| Integrative bioinformatics—interoperability, ontologies, semantics, databases and standards |
| Genomics of communities, meta-genomics of populations of cells and organisms |
| Molecular evolution, phylogeny and population genetics |
| Complex genotype–phenotype relationships—genome-wide association studies for human diseases and desirable traits in plants, animals and microbes |
| Data analysis—standard algorithms, basics of supervised and unsupervised statistical learning, data integration |
| Statistical inference—use of appropriate statistical tests, reverse engineering |
| Machine learning—clustering; neural networks, random forest |
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| Quantitative imaging/microscopy—single-cell analysis using flow cytometry or microscopy or spectroscopy, image analysis and quantification, cell variability analysis |
| Global and high-throughput data—genetic, transcriptome, proteome and metabolome |
| Biochemical |
| Handling and culturing of cells and organisms |
| Quantitative and time-resolved experimental methods at low throughput—levels and modifications of biomolecules, especially proteins and RNAs |
| Principles of system perturbations—genetic, experimental, pharmacological perturbations to test, challenge and control systems |
| Principles of systems engineering— |
(i) Mathematical and computational framework; (ii) networks and processes of life; (iii) scientific programming, (iv) bioinformatics and statistics; and (iv) experimental design, measurement, analysis, interpretation and knowledge generation. Each area is broken down into specific topics and the relevance in which it should be taught.
Skills that should be introduced to students entering a Systems Biology Programme from either an experimental (left) or theoretical (right) background
| Linear algebra: matrix representations of linear equations, matrix analysis, vector spaces, linear dependence/independence, linear combinations and spans, basis, eigenvalue and eigenvectors, linear transformations | The cell concept and cell organisation: cell diversity, prokaryotes and eukaryotes, organelles, cytoskeleton and cell structure |
| Differential and integral calculus: limits, derivatives, derivative properties, power rule, mean value theorem, integrals, fundamental theorem of calculus, area under the curve, series, sequences, | Basic and quantitative biochemistry and physiology: macromolecules, the function of membranes and membrane structure, what drives life: basics of thermodynamics, bioenergetics, metabolic pathways, catabolism and anabolism, basic protein structures, protein properties: enzymes, antibodies, affinities |
| Differential equations: first-order differential equations, directions fields, existence and uniqueness of solutions, separable equations, Laplace transformation | Genetics and inheritance: genomes and chromosomes, epigenetics, genetic variation, DNA replication and repair, viruses and transposable elements |
| Basics of graph theory and Boolean logics | Gene expression: from DNA to RNA: transcription, from RNA to proteins: translation, gene regulation |
| Structured programming, pseudo-code, data structures, flow diagrams | Cellular responses: receptors and signalling, cell division, apoptosis and cell death, protein sorting, protein secretion |
| Numerical analysis and algorithms: interpolation and numerical approximation of functions, methods for integration of functions and for solving ordinary and partial differential equations, methods for solving linear algebra problems, methods for solving systems of linear equations, Monte Carlo techniques, stochastic simulation algorithms | Multicellularity: the function of tissues, hormones, development, causes of disease |
| Multivariate calculus: double and triple integrals, volume under a surface, partial derivatives, gradients, divergence, surface integrals | Evolution: selection and adaptation, basic population genetics |
| Introduction to programming and algorithmics | Techniques: genetic model organisms, DNA technology and sequencing, DNA microarray |