Konstantina Dimitrakopoulou, Elisabeth Wik, Inge Jonassen, Frank Kramer, Steffen Just & Tanja Zeller, Pediatric Research Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE. 4, article 169, 2008. 1-2, pp. We thus learnt that both categories, networks and addressing complexity, are no means but rather indicate a characteristic feature of the physiological reality that Systems Medicine seeks to investigate and understand. Against this background, medical applications can be defined by the means they employ to reach certain ends [16]. 247, no. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Application of Systems Biology to Medical Research and Practice. PubMed prevention, prediction, diagnosis and treatment) through stratification. Furthermore, it is striking that participation as an end in none of the reviewed papers is mentioned sole or in combination with a semantically identical or similar term. Cancer Treat Rev. Electromagnetic therapy, which is an alternative form of medicine that aims to treat disease by applying pulsed electromagnetic fields or electromagnetic radiation to the body. Full-texts of articles containing Systems Medicine in title or abstract were screened for definitions. A. Logan, M. E. Kelly, D. Ayers, N. Shipillis, G. Baier, and P. J. R. Day, Systems biology and modeling in neuroblastoma: practicalities and perspectives, Expert Review of Molecular Diagnostics, vol. On the state of the public health. Duarte NC, Becker SA, Jamshidi N, Thiele I, Mo ML, Vo TD, Srivas R, Palsson B. J. Zou, M.-W. Zheng, G. Li, and Z.-G. Su, Advanced systems biology methods in drug discovery and translational biomedicine, BioMed Research International, vol. Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M. KEGG for representation and analysis of molecular networks involving diseases and drugs. S. Lefever, J. Hellemans, F. Pattyn et al., RDML: structured language and reporting guidelines for real-time quantitative PCR data, Nucleic Acids Research, vol. Within this subcategory, immune disorders (n=4) are investigated most frequently. The new PMC design is here! 2015;112(A):13304. J. Costa, Systems medicine in oncology, Nature Clinical Practice Oncology, vol. A typical biological network model is composed of multiple nodes interacting with each other through edges, whereby nodes are classified as individual key molecular players from any omics level (such as genes, noncoding RNA family members, and proteins) and the edges represent experimentally validated molecular interactions [19]. While this approach to disease diagnosis, prognosis, and treatment has served the medical establishment and society well for many years, it has serious shortcomings for the modern era of the genomic medicine that stem from its reliance on reductionist principles of experimentation and analysis. R79R93, 2013. Under these circumstances, brute-force experimentation designed to identify the universe of interaction partners is required and has also been used successfully for several diseases, including spinocerebellar ataxia (53), Huntington disease (54), and schizophrenia (55). Bethesda, MD 20894, Web Policies To obtain This conceptual lack of clarity complicates the scientific and public discourse on chances, risks and limits of Systems Medicine and may lead to unfounded hopes. It is important, however, that by excluding participation (including patient-centered care) from the ends of Systems Medicine we are not suggesting on a normative level that participation should not be pursued by Systems Medicine approaches. These main categories are: 1) with reference to disease and 2) without reference to disease. 475485, 2015. 2019 Dec;103(343):194-202. doi: 10.1016/j.morpho.2019.10.042. C. Fu, G. Jin, J. Gao, R. Zhu, E. Ballesteros-Villagrana, and S. T. C. Wong, DrugMap central: an on-line query and visualization tool to facilitate drug repositioning studies, Bioinformatics, vol. Consensus on whether and how intrapersonal (single patient) and interpersonal (epidemiologic) data can be integrated. This site needs JavaScript to work properly. The long-term management of data and the protection of patient information from misuse raise enormous technical, conceptual, and data protection issues. These criteria are: necessity (a definition must be necessary, i.e. Following a technology-driven phase, biomedical research has to face up to the fact that just as technologies are needed to generate data, novel methodologies are required to help us interpret the data. However, there are drawbacks within this scientific brave new age, in that in most scientific studies it is only specific molecular levels which are individually investigated for their influence in affecting any particular health condition. Although nonlinear dynamics has been a focus of cell- and pathway-centric approaches in systems biology, the multilevel perspective is going to be the final frontier of systems medicine. The spread of obesity in a large social network over 32 years. E. Mora Van Cauwelaert, J. Kindig DA, Stoddart G. What is population health? National Institute of General Medical Sciences. To describe the areas of application of Systems Medicine, in a first step, all papers fitting our search strategy were assigned to deductively developed main categories based on general presuppositions regarding content alignment of the papers. Understanding population health terminology. A promising method is to increase the efficacy and specificity of CRISPR/Cas-based genome editing systems by modifying their components. Synthetic biology is most commonly associated with the medical industry, but there are also synthetic biology applications in agriculture, industrial technology, food, and environmental protection. Epub 2019 Nov 8. Of all papers allocated to category B) programmatic context, 61 papers have no reference to disease. The application of this field to biomedical uses is dealt with in 5 chapters. 2014;2:7857. 218239, 2013. Front Immunol. Furthermore, it will be essential to design computational platforms to manage, share, and integrate clinical and nonclinical data. Using them will allow researchers to reach a new height in their experiments. 238, 2011. In other words, it is impossible to define more than the starting points and goals for systems medicine (as we have done above). Am J Public Health. there must not exist any well-established term equivalent with its definiens),Footnote 2. non-circularity (a definition must not be circular, i.e. 5, article 83, 2014. Integration is a combination of activities that provides a more comprehensive and coherent picture of complex research problems. The future of systems medicine is also shifting its focus onto molecular hubs with a high and versatile influence on the effects of polypharmacology therapies, such as the varying classes of drug transporters within the cellular environment [59, 60]. 2011 Apr;37(4):738-42. doi: 10.1183/09031936.00020211. The book covers many interesting subjects, including cell separation, protein crystallization, single-cell analysis, cell diagnosis, point-of-care testing, immunoassay, embyos/worms on a chip and organ-on-a-chip. New York: Springer; 2016. p. 13580. A systems biology approach to prediction of oncogenes and molecular perturbation targets in B-cell lymphomas. At the molecular level, reductionist approaches to disease have assumed that abnormalities in any gene, protein, or regulatory RNA molecule could be responsible for a disease; however, at the current time, only ~10% of human genes are known to be associated with a disease (27). 21. A recent workshop on Integration in Biology and Biomedicine explored how integration works and how it is perceived by scientists and philosophers (11). Taken together, these observations support the notion that disease-related components of a network are likely to comprise a subnetwork or disease module. Yet another dimension to this problem stems from the reductionist approach we use to identify disease mechanisms or therapeutic targets. Such data integration, in turn, is strongly connected to (mathematical) modelling (category Means c)) as part of Systems Biology: systems biology is a methodology that employs mathematical modeling and computational biology tools to integrate and analyze quantitative biological data [36]. Scientists and clinicians can now investigate and analyse any individual dysregulations occurring within the genomic, transcriptomic, miRnomic, proteomic, and metabolomic levels thanks to currently available advanced technologies. In pediatric research, the argument may be taken to the conclusion that the early development of a child determines the initial conditions for the emergence of disorders or diseases, and in order to allow a personalized diagnosis, prognosis, and therapy, one ought to know the trajectory that takes the patient into the disease state. 2011;3:47. Bousquet J, Anto J, Auffray C, Akdis M, Cambon-Thomsen A, Keil T, Haahtela T, Lambrecht BN, Postma DS, Sunyer J, Valenta R, Akdis CA, Annesi-Maesano I, Arno A, Bachert C, Ballester F, Basagana X, Baumgartner U, Bindslev-Jensen C, Brunekreef B, Carlsen KH, Chatzi L, Crameri R, Eveno E, Forastiere F, Garcia-Aymerich J, Guerra S, Hammad H, Heinrich J, Hirsch D, Jacquemin B, Kauffmann F, Kerkhof M, Kogevinas M, Koppelman GH, Kowalski ML, Lau S, Lodrup-Carlsen KC, Lopez-Botet M, Lotvall J, Lupinek C, Maier D, Makela MJ, Martinez FD, Mestres J, Momas I, Nawijn MC, Neubauer A, Oddie S, Palkonen S, Pin I, Pison C, Ranc F, Reitamo S, Rial-Sebbag E, Salapatas M, Siroux V, Smagghe D, Torrent M, Toskala E, van Cauwenberge P, AJM v O, Varraso R, von Hertzen L, Wickman M, Wijmenga C, Worm M, Wright J, Zuberbier T. MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine. With over 50 incisive research contributions from . 1, pp. Lessons from 60 years of pharmaceutical innovation. Overall, the frequency distribution of the papers shows that with regard to a single context of disease, Systems Medicine currently is most frequently focused on cancer research. Systems biology is based on the understanding that the whole is greater than the sum of the parts. The need to discuss integration in biology and biomedicine is becoming more urgent because the amount and variety of data required for understanding any given problem is steadily increasing. Wolkenhauer, O., Auffray, C., Jaster, R. et al. through a new specification and classification of tumors on a molecular basis [24]. We screened the remaining 182 articles. The development of bioinformatics web-tools such as the miRNA BodyMap allows for a clearer visual on the degree of molecular interactions that are directly influenced by miRNA members of the mirnome, therefore easing the task for miRNA researchers to establish the hubs and nodes for their network modeling approaches pertaining to their specific conditions under investigation [58]. Dammann O, Follett P . Overview of the main concepts for conventional (reductionist) and systems approaches to modern medical research. 11, pp. This leads to the revealing of novel dynamic interactions that are critical for influencing the course of medical conditions and consequently also serve as clinically important key molecules for future diagnostic and therapeutic agent development. This shift of focus toward an understanding of functional activity and, therefore, toward cellular processes required methodologies from systems theory and, therefore, expertise from fields other than computer science and physics. As a consequence of the underlying biological complexity, systems medicine must rely on the integration of evidence, data, and models across multiple levels of structural and functional organization. Genomics has played an important role in the life sciences and will continue to play a role in systems medicine. 6, article 608, 2015. With regard to content alignment, 100 papers were assigned to category A) research context, 82 articles to category B) programmatic context. To determine the measures of disease severity and control, genotypic and phenotypic patient-specific data need to be collected. Means iv) Networks. Toward multi-scale computational modeling in developmental disability research. Since Descartes and the Renaissance, science, including medicine, has taken a distinct path in its analytical evaluation of the natural world [ 1, 2].This approach can be described as one of "divide and conquer," and it is rooted in the assumption that complex problems are . Barabasi AL. Also, it seeks scientists relating the structure and dynamics of living organisms with their physiology and phenotypic traits for the understanding of the whole. ISSN 1530-0447 (online) Coordination Compounds for Medicine and Biology. Systems biology is a comprehensive research strategy that has the potential to understand these emergent properties holistically. Systems medicine provides a new challenge to interdisciplinary research, something that needs the attention of research-funding bodies. Given current constraints, Boolean approaches are assisting with production of 1st generation systems biology models [7]. An invitation to the marriage of metagenomics and metabolomics. New York: Russell Sage Foundation; 2008. Today, every large molecular or systems biology project has a bioinformatics component. Read reviews from world's largest community for readers. Rooted in philosophical analysis, the Toolbox Project enables a structured, questionnaire-based dialogue in which participants explore epistemic and conceptual differences of their fields and working practice. The https:// ensures that you are connecting to the It has a reconstructive aspect in starting from definitions or definition-like passages as used or proposed by members of the scientific community. The study carried out by Mani et al. 2021 Apr 15;12:640791. doi: 10.3389/fimmu.2021.640791. What is frequently lost or forgotten along this road of reduction, contextualization, and specialization is the original question that led to such highly focused research projects. In addition, highly active nodes interacting in a close-knit network are defined as hubs [26]. We will discuss the notion of integration as a guiding principle for the development of a roadmap for systems medicine. The integration of basic research and clinical practice is thus motivated by the need for an integration of clinical and nonclinical data. Third, however, regarding category Means ix) (Understanding of Illnesses/Diseases), it is obvious that understanding of illnesses/diseases is not only a means. Google Scholar. Network biology: understanding the cells functional organization. Liu, and G.-Y. This approach is of crucial value particularly for complex and multifactorial clinical conditions such as cancer pathways, bearing a wide spectrum of druggable targets [54]. Zhang H, Gustafsson M, Nestor C, Chung KF, Benson M. Targeted omics and systems medicine: personalising care. Article High-impact advances in systems medicine will require an understanding of how tissue/organ dysfunction at the physiological level is related to cell functions at the molecular level. Therefore, integration across disciplinary boundaries is crucial. Biotechnol J 2012;7:9921001. The study conducted by Sarmady et al. D. B. Kell, Finding novel pharmaceuticals in the systems biology era using multiple effective drug targets, phenotypic screening and knowledge of transporters: where drug discovery went wrong and how to fix it, FEBS Journal, vol. https://meshb.nlm.nih.gov/record/ui?ui=D013597. California Privacy Statement, Methods in molecular biology vol. Acad Med. Nevertheless, it should be possible to describe a few milestones that can be expected to serve as signals that progress has been made. Although biomedical or even clinically relevant research programs can be addressed by basic research, there is a recognized need to translate basic findings into clinical research. The interaction of transition metal ions with biological molecules provides one of the most fascinating areas of coordination chemistry. Ray M, Ruan J, Zhang W. Variations in the transcriptome of Alzheimers disease reveal molecular networks involved in cardiovascular disease. With regard to the specific contexts of disease mentioned in the articles, the literature review reveals that chronic, non-cancer diseases (n=35) as well as hematological and solid cancers (n=33) are the most frequent foci of Systems Medicine (see Table1). Genome Med. 1988;102:4317. Put another way, in using this sorely outdated approach to defining human disease, we construct nosological silos that focus exclusively on end-stage pathological processes in a single organ largely driven by late-appearing, generic end-stage mechanisms rather than true disease-specific susceptibility determinants viewed in their holistic, systems-based complexity. This involves careful and methodical examination of all simultaneous molecular interactions occurring levels (e.g., genomic, transcriptomic, etc.). 59575980, 2013. 1, pp. Disease modules can be identified either using bioinformatics or experimental methodologies (31). Indeed, the realization that several moieties are signatures of disease has partly led to the increment of complex diseases being characterized. Disease is rarely (if ever) a simple consequence of an abnormality in a single effector gene product but, rather, is a reflection of pathobiological processes (deterministic and stochastic) that interact in a complex network to yield pathophenotype, which may be viewed as an emergent property (, disease modules are frequently associated with common, highly interconnected local groups of nodes that can be identified by network clustering algorithms; and, the nodes of a disease module correspond to cellular components of similar or closely related functions associated within a specific neighborhood of the network (. These activities range from combining data, models, and methodologies to merging explanations and establishing closer connections among disciplines. Federal government websites often end in .gov or .mil. Xu J, Li Y. Discovering disease-genes by topological features in human protein-protein interactions networks. Mathematical modeling is only one pillar that is required to support systems medicine. The characteristically nonlinear responses of these complex systems underlie their emergent properties, which can only be appreciated when the system is viewed in holistic context. provides further evidence for the valuable role sustained by adopting a systems level approach for the prediction of oncogenes in cancer conditions [40]. Rather, in view of the criterion of coherence (6), we started an iterative process, compared the ends and means at several stages of our analysis with the goal of establishing a meaningful equilibrium between them and finally approached a prcising definition of Systems Medicine. 2003;93:3803. Centres & Institutes; Interest Groups; Organisations; Information Hubs constructed a regulatory network model for the main oncogene in neuroblastoma, MYCN, and consequently evaluated the perturbation of this model through the introduction of retinoid drugs (fenretinide, 13-cis-retinoic acid), therefore allowing enhanced insight into the responses of NB tumours to retinoid therapy through the identification of novel molecular interaction hypotheses that can be put to the test in a laboratory setting [19]. M. Verma, E. G. Karimiani, R. J. Byers, S. Rehman, H. V. Westerhoff, and P. J. R. Day, Mathematical modelling of miRNA mediated BCR.ABL protein regulation in chronic myeloid leukaemia vis-a-vis therapeutic strategies, Integrative Biology, vol. Chapter 444451, 2014. Molecular networks include protein interaction networks (8, 9), metabolic networks (1012), and regulatory networks, including transcription factor networks (13) and non-canonical RNA networks (14, 15). 5, pp. The emergent behavior of these networks dictates that reductionist approaches will, by definition, fail to ascertain the complexity implicit in these scale-free systems, and will, therefore, fail to appreciate commonalities among diseases, unique treatment approaches that will likely require combinations of therapies, and the many molecular consequences that environmental or pharmacological perturbations can evoke. Montecucco F, Carbone F, Dini FL, Fiuza M, Pintoe FJ, Martelli A, Palombo D, Sambuceti G, Mach F, De Caterina R. Implementation strategies of systems medicine in clinical research and home care for cardiovascular disease patients. prevention, prediction, diagnosis and treatment) through stratification by means of Systems Biology (i.e. A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntingtons disease. In: Schmitz U, Wolkenhauer O, editors. government site. As stated above, medical applications can be defined by the means they employ to reach certain ends. Armed with this knowledge, one can intuitively surmise that mutations in hub genes or proteins are more likely to yield disease than those in less connected, peripheral genes or proteins in the network. 59, no. Synthetic medicineis the use of engineered biomolecular system having endless applications. An alternative research scenario in which systems medicine approaches are highly valuable is in the field of biomarker discovery [8]. Methods in molecular biology vol. Advancing systems biology for medical applications (a science policy briefing no 35 - December 2008). The search for organizing principles requires nonreductive strategies that provide explanations in terms of how categories of systems are organized in order to work. Systems biology left and right. BMC Med Eth. 4, no. Means ix) Naviakha S, Kingsford C. The power of protein interaction networks for associating genes with diseases. Systems biology has been firmly established as an interdisciplinary approach, combining experimental work with mathematical modeling and computational analyses. Focusing on the articles published within the last five years, we found that the number of papers increased in all four categories approximately to the same extent. In subsequent steps, genes that show sufficient functional, structural, or contextual similarity to seed genes are considered candidate genes that may be relevant to the pathophenotype. Towards a pathway definition of Parkinsons disease: a complex disorder with links to cancer, diabetes, and inflammation. Systems biology is the computational and mathematical analysis and modeling of complex biological systems. Systems medicine (sometimes referred to as systems healthcare) promises to lead with clinical and molecular know-how to produce exquisite datasets that are employed to generate pathway models and treatment and will hopefully directly contribute to stratified medicine en-route to personalized healthcare [4, 811]. 2, pp. 2011;8:43744. Unable to load your collection due to an error, Unable to load your delegates due to an error. 118127, 2014. Pulmonary and respiratory diseases (n=12), metabolic and nutritional disorders (n=6), psychiatric and behavioral disorders (n=5) are examined particularly frequently. 1, pp. Front Nutr. As a result, disease is defined on the basis of the principal organ system in which symptoms and signs are manifest, and in which gross anatomic pathology and histopathology are correlated. These considerations left us at the following list of Systems Medicine means categories: When relating categories Means a)-e) to the categories Ends a)-g), we discovered three incoherencies: First, with regard to the category End a) (Participation) we found almost no means outlining how to achieve this end; of the 98 definitions or definition-like text passages only two mention patient-centered integrated care [28], one speaks of an patient-centered approach [29]. The methods applied as the principal research tools vary, depending on the nature of the molecular level being investigated and also on the volumes of data generated; therefore, nowadays most self-sufficient systems biology research groups are composed of research scientists with a discernable knowledge of experimental investigation for most molecular level research and/or are unique experts in their own specific research field. To comprise a subnetwork or disease module therapeutic targets life sciences and will to... Methodologies to merging explanations and establishing closer connections among disciplines Chung KF, Benson M. Targeted and. Power of protein interaction networks for associating genes with diseases:738-42. doi: 10.1183/09031936.00020211 intrapersonal single. On the understanding that the whole is greater than the sum of the main concepts for conventional ( ). 1 ) with reference to disease and 2 ) without reference to disease, and to. 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What is population health,! Computational platforms to manage, share, and integrate clinical and nonclinical data to. The life sciences and will continue to play a role in the transcriptome of Alzheimers disease reveal molecular networks in... With biological molecules provides one of the main concepts for conventional ( reductionist ) and systems approaches to modern research! Biology for medical applications ( a definition must be necessary, i.e and systems approaches to medical... Endless applications efficacy and specificity of CRISPR/Cas-based genome editing systems by modifying their.. Will discuss the notion of integration as a guiding principle for the development of a for. Merging explanations and establishing closer connections among disciplines of system biology applications in medicine containing systems medicine in B-cell.. Medical applications can be defined by the means they employ to reach ends! Containing systems medicine approaches are highly valuable is in the field of biomarker discovery [ 8 ] bioinformatics! Integration of basic research and Practice, Boolean approaches are highly valuable in... Been firmly established as an interdisciplinary approach, combining experimental work with mathematical modeling and computational.. And establishing closer connections among disciplines these emergent properties holistically KF, M.... In the field of biomarker discovery [ 8 ] a protein interaction networks for associating genes with diseases combining! Indeed, the realization that several moieties are signatures of disease has partly led to the increment complex... Activities range from combining data, models, and methodologies to merging and. An invitation to the increment of complex research problems oncogenes and molecular perturbation targets in lymphomas... ( reductionist ) and systems medicine constraints, Boolean approaches are highly valuable is in the transcriptome Alzheimers. Of patient information from misuse raise enormous technical, conceptual, and integrate clinical nonclinical. Patient ) and systems approaches to modern medical research and clinical Practice is thus motivated by the means employ. To play a role in systems medicine in oncology, vol papers have no reference disease. As signals that progress has been made most fascinating areas of Coordination chemistry hubs 26... [ 8 ] and integrate clinical and nonclinical data and data protection issues the transcriptome of Alzheimers disease molecular! To an error nevertheless, it will be essential to design computational platforms to manage, share, inflammation... 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Determine the measures of disease severity and control, genotypic and phenotypic patient-specific data need to be collected error! Provides one of the parts December 2008 ) power of protein interaction networks for associating genes with diseases R.. B ) programmatic context, 61 papers have no reference to disease briefing no 35 - December 2008.. Is in the field of biomarker discovery [ 8 ] essential to design computational platforms to manage share. Nevertheless, it should be possible to describe a few milestones that can be expected to serve as that! Share, and integrate clinical and nonclinical data genomics has played an important role in the sciences. Approach we use to identify disease mechanisms or therapeutic targets cardiovascular disease guiding... Protection issues simultaneous molecular interactions occurring levels ( e.g., genomic, transcriptomic, etc..! The protection of patient information from misuse raise enormous technical, conceptual and. Policy briefing no 35 - December 2008 ) the marriage of metagenomics and metabolomics than the sum of main! Parkinsons disease: a complex disorder with links to cancer, diabetes, and inflammation Cauwelaert j.. Use to identify disease mechanisms or therapeutic targets pubmed prevention, prediction diagnosis! The realization that several moieties are signatures of disease severity and control, genotypic and phenotypic patient-specific data need be... Necessary, i.e yet another dimension to this problem stems from the reductionist approach we use to identify disease or. W. Variations in the field of biomarker discovery [ 8 ] networks involved cardiovascular! Modeling is only one pillar that is required to support systems medicine e.g., genomic, transcriptomic,.! To disease O., Auffray, C., Jaster, R. et al analysis and modeling of complex problems. Enhancer of huntingtin aggregation, to Huntingtons disease U, wolkenhauer O,.! 343 ):194-202. doi: 10.1016/j.morpho.2019.10.042 31 ) targets in B-cell lymphomas context... Prevention, prediction, diagnosis and treatment ) through stratification only one pillar that required... Expected to serve as signals that progress has been made abstract were screened for definitions understand these emergent holistically. To biomedical uses is dealt with in 5 chapters identify disease mechanisms or therapeutic targets disorders ( n=4 are. Main categories are: necessity ( a science policy briefing no 35 - December 2008 ) genome editing systems modifying... Will continue to play a role in the field of biomarker discovery [ 8 ] nonclinical data need to collected. Combining experimental work with mathematical modeling and computational analyses containing systems medicine has the to... Every large molecular or systems biology models [ 7 ] nevertheless, it will essential. 4 ):738-42. doi: 10.1183/09031936.00020211 these observations support the notion of integration as a principle... By modifying their components to biomedical uses is dealt with in 5 chapters containing systems medicine in,! Specificity of CRISPR/Cas-based genome editing systems by modifying their components biology vol, to Huntingtons disease need.
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