Wiley Interdisciplinary Reviews-Systems Biology and Medicine最新文献

{"title":"Agent-based models of inflammation in translational systems biology: A decade later.","authors":"Yoram Vodovotz, Gary An","doi":"10.1002/wsbm.1460","DOIUrl":"10.1002/wsbm.1460","url":null,"abstract":"<p><p>Agent-based modeling is a rule-based, discrete-event, and spatially explicit computational modeling method that employs computational objects that instantiate the rules and interactions among the individual components (\"agents\") of system. Agent-based modeling is well suited to translating into a computational model the knowledge generated from basic science research, particularly with respect to translating across scales the mechanisms of cellular behavior into aggregated cell population dynamics manifesting at the tissue and organ level. This capacity has made agent-based modeling an integral method in translational systems biology (TSB), an approach that uses multiscale dynamic computational modeling to explicitly represent disease processes in a clinically relevant fashion. The initial work in the early 2000s using agent-based models (ABMs) in TSB focused on examining acute inflammation and its intersection with wound healing; the decade since has seen vast growth in both the application of agent-based modeling to a wide array of disease processes as well as methodological advancements in the use and analysis of ABM. This report presents an update on an earlier review of ABMs in TSB and presents examples of exciting progress in the modeling of various organs and diseases that involve inflammation. This review also describes developments that integrate the use of ABMs with cutting-edge technologies such as high-performance computing, machine learning, and artificial intelligence, with a view toward the future integration of these methodologies. This article is categorized under: Translational, Genomic, and Systems Medicine > Translational Medicine Models of Systems Properties and Processes > Mechanistic Models Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models Models of Systems Properties and Processes > Organismal Models.</p>","PeriodicalId":49254,"journal":{"name":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","volume":"11 6","pages":"e1460"},"PeriodicalIF":7.9,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140858/pdf/nihms-1702958.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37379291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidomics: Current state of the art in a fast moving field","authors":"V. O’Donnell, K. Ekroos, G. Liebisch, M. Wakelam","doi":"10.1002/wsbm.1466","DOIUrl":"https://doi.org/10.1002/wsbm.1466","url":null,"abstract":"Lipids are essential for all facets of life. They play three major roles: energy metabolism, structural, and signaling. They are dynamic molecules strongly influenced by endogenous and exogenous factors including genetics, diet, age, lifestyle, drugs, disease and inflammation. As precision medicine starts to become mainstream, there is a huge burgeoning interest in lipids and their potential to act as unique biomarkers or prognostic indicators. Lipids comprise a large component of all metabolites (around one‐third), and our expanding knowledge about their dynamic behavior is fueling the hope that mapping their regulatory biochemical pathways on a systems level will revolutionize our ability to prevent, diagnose, and stratify major human diseases. Up to now, clinical lipid measurements have consisted primarily of total cholesterol or triglycerides, as a measure for cardiovascular risk and response to lipid lowering drugs. Nowadays, we are able to measure thousands of individual lipids that make up the lipidome. nuclear magnetic resonance spectrometry (NMR) metabolomics is also being increasingly used in large cohort studies where it can report on total levels of selected lipid classes, and relative levels of fatty acid saturation. To support the application of lipidomics research, LIPID MAPS was established in 2003, and since then has gone on to become the go‐to resource for several lipid databases, lipid drawing tools, data deposition, and more recently lipidomics informatics tools, and a lipid biochemistry encyclopedia, LipidWeb. Alongside this, the recently established Lipidomics Standards Initiative plays a key role in standardization of lipidomics methodologies.","PeriodicalId":49254,"journal":{"name":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","volume":"98 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2019-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89260168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Going low to reach high: Small‐scale ChIP‐seq maps new terrain","authors":"Madeleine Fosslie, Adeel Manaf, Mads Lerdrup, K. Hansen, G. Gilfillan, J. Dahl","doi":"10.1002/wsbm.1465","DOIUrl":"https://doi.org/10.1002/wsbm.1465","url":null,"abstract":"Chromatin immunoprecipitation (ChIP) enables mapping of specific histone modifications or chromatin‐associated factors in the genome and represents a powerful tool in the study of chromatin and genome regulation. Importantly, recent technological advances that couple ChIP with whole‐genome high‐throughput sequencing (ChIP‐seq) now allow the mapping of chromatin factors throughout the genome. However, the requirement for large amounts of ChIP‐seq input material has long made it challenging to assess chromatin profiles of cell types only available in limited numbers. For many cell types, it is not feasible to reach high numbers when collecting them as homogeneous cell populations in vivo. Nonetheless, it is an advantage to work with pure cell populations to reach robust biological conclusions. Here, we review (a) how ChIP protocols have been scaled down for use with as little as a few hundred cells; (b) which considerations to be aware of when preparing small‐scale ChIP‐seq and analyzing data; and (c) the potential of small‐scale ChIP‐seq datasets for elucidating chromatin dynamics in various biological systems, including some examples such as oocyte maturation and preimplantation embryo development.","PeriodicalId":49254,"journal":{"name":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","volume":"1 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2019-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89403934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium signals that determine vascular resistance.","authors":"Matteo Ottolini, Kwangseok Hong, Swapnil K Sonkusare","doi":"10.1002/wsbm.1448","DOIUrl":"10.1002/wsbm.1448","url":null,"abstract":"<p><p>Small arteries in the body control vascular resistance, and therefore, blood pressure and blood flow. Endothelial and smooth muscle cells in the arterial walls respond to various stimuli by altering the vascular resistance on a moment to moment basis. Smooth muscle cells can directly influence arterial diameter by contracting or relaxing, whereas endothelial cells that line the inner walls of the arteries modulate the contractile state of surrounding smooth muscle cells. Cytosolic calcium is a key driver of endothelial and smooth muscle cell functions. Cytosolic calcium can be increased either by calcium release from intracellular stores through IP3 or ryanodine receptors, or the influx of extracellular calcium through ion channels at the cell membrane. Depending on the cell type, spatial localization, source of a calcium signal, and the calcium-sensitive target activated, a particular calcium signal can dilate or constrict the arteries. Calcium signals in the vasculature can be classified into several types based on their source, kinetics, and spatial and temporal properties. The calcium signaling mechanisms in smooth muscle and endothelial cells have been extensively studied in the native or freshly isolated cells, therefore, this review is limited to the discussions of studies in native or freshly isolated cells. This article is categorized under: Biological Mechanisms > Cell Signaling Laboratory Methods and Technologies > Imaging Models of Systems Properties and Processes > Mechanistic Models.</p>","PeriodicalId":49254,"journal":{"name":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","volume":"11 5","pages":"e1448"},"PeriodicalIF":7.9,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688910/pdf/nihms-1015195.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37067374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian rhythms and proteomics: It's all about posttranslational modifications!","authors":"Daniel Mauvoisin","doi":"10.1002/wsbm.1450","DOIUrl":"https://doi.org/10.1002/wsbm.1450","url":null,"abstract":"<p><p>The circadian clock is a molecular endogenous timekeeping system and allows organisms to adjust their physiology and behavior to the geophysical time. Organized hierarchically, the master clock in the suprachiasmatic nuclei, coordinates peripheral clocks, via direct, or indirect signals. In peripheral organs, such as the liver, the circadian clock coordinates gene expression, notably metabolic gene expression, from transcriptional to posttranslational level. The metabolism in return feeds back on the molecular circadian clock via posttranslational-based mechanisms. During the last two decades, circadian gene expression studies have mostly been relying primarily on genomics or transcriptomics approaches and transcriptome analyses of multiple organs/tissues have revealed that the majority of protein-coding genes display circadian rhythms in a tissue specific manner. More recently, new advances in mass spectrometry offered circadian proteomics new perspectives, that is, the possibilities of performing large scale proteomic studies at cellular and subcellular levels, but also at the posttranslational modification level. With important implications in metabolic health, cell signaling has been shown to be highly relevant to circadian rhythms. Moreover, comprehensive characterization studies of posttranslational modifications are emerging and as a result, cell signaling processes are expected to be more deeply characterized and understood in the coming years with the use of proteomics. This review summarizes the work studying diurnally rhythmic or circadian gene expression performed at the protein level. Based on the knowledge brought by circadian proteomics studies, this review will also discuss the role of posttranslational modification events as an important link between the molecular circadian clock and metabolic regulation. This article is categorized under: Laboratory Methods and Technologies > Proteomics Methods Physiology > Mammalian Physiology in Health and Disease Biological Mechanisms > Cell Signaling.</p>","PeriodicalId":49254,"journal":{"name":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","volume":"11 5","pages":"e1450"},"PeriodicalIF":7.9,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wsbm.1450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37192184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential contributions of enhancer genomic regulatory elements to microglial cell identity and functions.","authors":"André Machado Xavier,&nbsp;Sarah Belhocine,&nbsp;David Gosselin","doi":"10.1002/wsbm.1449","DOIUrl":"https://doi.org/10.1002/wsbm.1449","url":null,"abstract":"<p><p>Microglia are the specialized macrophages of the brain and play essential roles in ensuring its proper functioning. Accumulating evidence suggests that these cells coordinate the inflammatory response that accompanies various clinical brain conditions, including neurodegenerative diseases and psychiatric disorders. Therefore, investigating the functions of these cells and how these are regulated have become important areas of research in neuroscience over the past decade. In this regards, recent efforts to characterize the epigenomic mechanisms underlying microglial gene transcription have provided significant insights into the mechanisms that control the ontogeny and the cellular competences of microglia. In particular, these studies have established that a substantial proportion of the microglial repertoire of promoter-distal genomic regulatory elements, or enhancers, is relatively specific to these cells compared to other tissue-resident macrophages. Notably, this specificity is under the regulation of factors present in the brain that modulate activity of target axes of signaling pathways-transcription factors in microglia. Thus, the microglial enhancer repertoire is highly responsive to perturbations in the cerebral tissue microenvironment and this responsiveness has profound implications on the activity of these cells in brain diseases. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Models of Systems Properties and Processes > Mechanistic Models Biological Mechanisms > Cell Fates Developmental Biology > Lineages.</p>","PeriodicalId":49254,"journal":{"name":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","volume":"11 5","pages":"e1449"},"PeriodicalIF":7.9,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wsbm.1449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37356462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL7 receptor signaling in T cells: A mathematical modeling perspective.","authors":"Jung-Hyun Park,&nbsp;Adam T Waickman,&nbsp;Joseph Reynolds,&nbsp;Mario Castro,&nbsp;Carmen Molina-París","doi":"10.1002/wsbm.1447","DOIUrl":"https://doi.org/10.1002/wsbm.1447","url":null,"abstract":"<p><p>Interleukin-7 (IL7) plays a nonredundant role in T cell survival and homeostasis, which is illustrated in the severe T cell lymphopenia of IL7-deficient mice, or demonstrated in animals or humans that lack expression of either the IL7Rα or γ _c chain, the two subunits that constitute the functional IL7 receptor. Remarkably, IL7 is not expressed by T cells themselves, but produced in limited amounts by radio-resistant stromal cells. Thus, T cells need to constantly compete for IL7 to survive. How T cells maintain homeostasis and further maximize the size of the peripheral T cell pool in face of such competition are important questions that have fascinated both immunologists and mathematicians for a long time. Exceptionally, IL7 downregulates expression of its own receptor, so that IL7-signaled T cells do not consume extracellular IL7, and thus, the remaining extracellular IL7 can be shared among unsignaled T cells. Such an altruistic behavior of the IL7Rα chain is quite unique among members of the γ _c cytokine receptor family. However, the consequences of this altruistic signaling behavior at the molecular, single cell and population levels are less well understood and require further investigation. In this regard, mathematical modeling of how a limited resource can be shared, while maintaining the clonal diversity of the T cell pool, can help decipher the molecular or cellular mechanisms that regulate T cell homeostasis. Thus, the current review aims to provide a mathematical modeling perspective of IL7-dependent T cell homeostasis at the molecular, cellular and population levels, in the context of recent advances in our understanding of the IL7 biology. This article is categorized under: Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models Biological Mechanisms > Cell Signaling Models of Systems Properties and Processes > Mechanistic Models Analytical and Computational Methods > Computational Methods.</p>","PeriodicalId":49254,"journal":{"name":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","volume":"11 5","pages":"e1447"},"PeriodicalIF":7.9,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wsbm.1447","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37284767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI in systems medicine","authors":"Thomas T. Liu","doi":"10.1002/wsbm.1463","DOIUrl":"https://doi.org/10.1002/wsbm.1463","url":null,"abstract":"Magnetic resonance imaging (MRI) is one of the primary medical imaging modalities and a key component of the standard of care in modern healthcare systems. One of the factors that distinguishes MRI from other imaging methods is the ability to program the MRI system to reveal a wide range of imaging contrasts, where each type of contrast offers unique information about the biological sample of interest. This ability stems from the fact that both the amplitude and phase of the magnetization of the underlying tissue can be manipulated to highlight different biological phenomenon. The flexibility and capabilities offered by modern MRI systems have enabled the development of a myriad of techniques for characterizing anatomy, physiology, and function. These include methods to characterize gross anatomy, tissue microstructure, bulk blood flow, tissue perfusion, and functional changes in blood oxygenation.","PeriodicalId":49254,"journal":{"name":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","volume":"74 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2019-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89611195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advancement of light-based single-molecule approaches for studying biomolecules.","authors":"Benjamin Croop,&nbsp;Chenyi Zhang,&nbsp;Youngbin Lim,&nbsp;Ryan M Gelfand,&nbsp;Kyu Young Han","doi":"10.1002/wsbm.1445","DOIUrl":"https://doi.org/10.1002/wsbm.1445","url":null,"abstract":"<p><p>Recent advances in single-molecule techniques have led to new discoveries in analytical chemistry, biophysics, and medicine. Understanding the structure and behavior of single biomolecules provides a wealth of information compared to studying large ensembles. However, developing single-molecule techniques is challenging and requires advances in optics, engineering, biology, and chemistry. In this paper, we will review the state of the art in single-molecule applications with a focus over the last few years of development. The advancements covered will mainly include light-based in vitro methods, and we will discuss the fundamentals of each with a focus on the platforms themselves. We will also summarize their limitations and current and future applications to the wider biological and chemical fields. This article is categorized under: Laboratory Methods and Technologies > Imaging Laboratory Methods and Technologies > Macromolecular Interactions, Methods Analytical and Computational Methods > Analytical Methods.</p>","PeriodicalId":49254,"journal":{"name":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","volume":"11 4","pages":"e1445"},"PeriodicalIF":7.9,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wsbm.1445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36922665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Models of polymer physics for the architecture of the cell nucleus.","authors":"Andrea Esposito,&nbsp;Carlo Annunziatella,&nbsp;Simona Bianco,&nbsp;Andrea M Chiariello,&nbsp;Luca Fiorillo,&nbsp;Mario Nicodemi","doi":"10.1002/wsbm.1444","DOIUrl":"10.1002/wsbm.1444","url":null,"abstract":"<p><p>The depth and complexity of data now available on chromosome 3D architecture, derived by new technologies such as Hi-C, have triggered the development of models based on polymer physics to explain the observed patterns and the underlying molecular folding mechanisms. Here, we give an overview of some of the ideas and models from physics introduced to date, along with their progresses and limitations in the description of experimental data. In particular, we focus on the Strings&Binders and the Loop Extrusion model of chromatin architecture. This article is categorized under: Analytical and Computational Methods > Computational Methods.</p>","PeriodicalId":49254,"journal":{"name":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","volume":"11 4","pages":"e1444"},"PeriodicalIF":7.9,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wsbm.1444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36796593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}