BACKGROUND: Integration of multi-omics data can provide a more complex view of the biological system consisting of different interconnected molecular components, the crucial aspect for developing novel personalised therapeutic strategies for complex diseases. Various tools have been developed to integrate multi-omics data. However, an efficient multi-omics framework for regulatory network inference at the genome level that incorporates prior knowledge is still to emerge. RESULTS: We present IntOMICS, an efficient integrative framework based on Bayesian networks. IntOMICS systematically analyses gene expression, DNA methylation, copy number variation and biological prior knowledge to infer regulatory networks. IntOMICS complements the missing biological prior knowledge by so-called empirical biological knowledge, estimated from the available experimental data. Regulatory networks derived from IntOMICS provide deeper insights into the complex flow of genetic information on top of the increasing accuracy trend compared to a published algorithm designed exclusively for gene expression data. The ability to capture relevant crosstalks between multi-omics modalities is verified using known associations in microsatellite stable/instable colon cancer samples. Additionally, IntOMICS performance is compared with two algorithms for multi-omics regulatory network inference that can also incorporate prior knowledge in the inference framework. IntOMICS is also applied to detect potential predictive biomarkers in microsatellite stable stage III colon cancer samples. CONCLUSIONS: We provide IntOMICS, a framework for multi-omics data integration using a novel approach to biological knowledge discovery. IntOMICS is a powerful resource for exploratory systems biology and can provide valuable insights into the complex mechanisms of biological processes that have a vital role in personalised medicine.
- MeSH
- algoritmy MeSH
- Bayesova věta MeSH
- genové regulační sítě MeSH
- lidé MeSH
- nádory tračníku * MeSH
- systémová biologie metody MeSH
- variabilita počtu kopií segmentů DNA * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Dynamic modeling of biological systems is essential for understanding all properties of a given organism as it allows us to look not only at the static picture of an organism but also at its behavior under various conditions. With the increasing amount of experimental data, the number of tools that enable dynamic analysis also grows. However, various tools are based on different approaches, use different types of data and offer different functions for analyses; so it can be difficult to choose the most suitable tool for a selected type of model. Here, we bring a brief overview containing descriptions of 50 tools for the reconstruction of biological models, their time-course simulation and dynamic analysis. We examined each tool using test data and divided them based on the qualitative and quantitative nature of the mathematical apparatus they use.
- MeSH
- biologické modely * MeSH
- datové soubory jako téma MeSH
- genové regulační sítě MeSH
- lidé MeSH
- počítačová simulace MeSH
- software * MeSH
- stochastické procesy MeSH
- systémová biologie metody MeSH
- ukládání a vyhledávání informací MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Despite over a decade of cystic fibrosis (CF) microbiome research, much remains to be learned about the overall composition, metabolic activities, and pathogenicity of the microbes in CF airways, limiting our understanding of the respiratory microbiome's relation to disease. Systems-level integration and modeling of host-microbiome interactions may allow us to better define the relationships between microbiological characteristics, disease status, and treatment response. In this way, modeling could pave the way for microbiome-based development of predictive models, individualized treatment plans, and novel therapeutic approaches, potentially serving as a paradigm for approaching other chronic infections. In this review, we describe the challenges facing this effort and propose research priorities for a systems biology approach to CF lung disease.
- MeSH
- Bacteria izolace a purifikace metabolismus MeSH
- cystická fibróza mikrobiologie terapie MeSH
- lidé MeSH
- mikrobiota MeSH
- plíce mikrobiologie MeSH
- systémová biologie metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: A statistical pipeline was developed and used for determining candidate genes and candidate gene coexpression networks involved in 2 alcohol (i.e., ethanol [EtOH]) metabolism phenotypes, namely alcohol clearance and acetate area under the curve in a recombinant inbred (RI) (HXB/BXH) rat panel. The approach was also used to provide an indication of how EtOH metabolism can impact the normal function of the identified networks. METHODS: RNA was extracted from alcohol-naïve liver tissue of 30 strains of HXB/BXH RI rats. The reconstructed transcripts were quantitated, and data were used to construct gene coexpression modules and networks. A separate group of rats, comprising the same 30 strains, were injected with EtOH (2 g/kg) for measurement of blood EtOH and acetate levels. These data were used for quantitative trait loci (QTL) analysis of the rate of EtOH disappearance and circulating acetate levels. The analysis pipeline required calculation of the module eigengene values, the correction of these values with EtOH metabolism rates and acetate levels across the rat strains, and the determination of the eigengene QTLs. For a module to be considered a candidate for determining phenotype, the module eigengene values had to have significant correlation with the strain phenotypic values and the module eigengene QTLs had to overlap the phenotypic QTLs. RESULTS: Of the 658 transcript coexpression modules generated from liver RNA sequencing data, a single module satisfied all criteria for being a candidate for determining the alcohol clearance trait. This module contained 2 alcohol dehydrogenase genes, including the gene whose product was previously shown to be responsible for the majority of alcohol elimination in the rat. This module was also the only module identified as a candidate for influencing circulating acetate levels. This module was also linked to the process of generation and utilization of retinoic acid as related to the autonomous immune response. CONCLUSIONS: We propose that our analytical pipeline can successfully identify genetic regions and transcripts which predispose a particular phenotype and our analysis provides functional context for coexpression module components.
- MeSH
- ethanol aplikace a dávkování metabolismus MeSH
- játra účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- metabolická clearance účinky léků fyziologie MeSH
- multifaktoriální dědičnost účinky léků fyziologie MeSH
- pití alkoholu genetika metabolismus MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- potkani transgenní MeSH
- strojové učení bez učitele * MeSH
- systémová biologie metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Here, we describe a method for the combined metabolomic, proteomic, transcriptomic and genomic analysis from one single sample as a major step for multilevel data integration strategies in systems biology. While extracting proteins and DNA, this protocol also allows the separation of metabolites into polar and lipid fractions, as well as RNA fractionation into long and small RNAs, thus allowing a broad range of transcriptional studies. The isolated biomolecules are suitable for analysis with different methods that range from electrophoresis and blotting to state-of-the-art procedures based on mass spectrometry (accurate metabolite profiling, shot-gun proteomics) or massive sequencing technologies (transcript analysis). The low amount of starting tissue, its cost-efficiency compared with the utilization of commercial kits, and its performance over a wide range of plant, microbial, and algal species such as Chlamydomonas, Arabidopsis, Populus, or Pinus, makes this method a universal alternative for multiple molecular isolation from plant tissues.
- MeSH
- Arabidopsis genetika metabolismus MeSH
- borovice genetika metabolismus MeSH
- Chlamydomonas reinhardtii genetika metabolismus MeSH
- DNA rostlinná izolace a purifikace MeSH
- genomika metody MeSH
- metabolomika metody MeSH
- Populus genetika metabolismus MeSH
- proteomika metody MeSH
- reprodukovatelnost výsledků MeSH
- RNA rostlin izolace a purifikace MeSH
- rostlinné proteiny izolace a purifikace MeSH
- rostliny * genetika metabolismus MeSH
- systémová biologie metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
E-photosynthesis framework is a web-based platform for modeling and analysis of photosynthetic processes. Compared to its earlier version, the present platform employs advanced software methods and technologies to support an effective implementation of vastly diverse kinetic models of photosynthesis. We report on the first phase implementation of the tool new version and demonstrate the functionalities of model visualization, presentation of model components, rate constants, initial conditions and of model annotation. The demonstration also includes export of a model to the Systems Biology Markup Language format and remote numerical simulation of the model.
- MeSH
- biomedicínské inženýrství metody trendy MeSH
- financování organizované MeSH
- kardiovaskulární systém MeSH
- lidé MeSH
- modely kardiovaskulární MeSH
- systémová analýza MeSH
- systémová biologie metody trendy MeSH
- systémová teorie MeSH
- teoretické modely MeSH
- zpětná vazba fyziologie MeSH
- Check Tag
- lidé MeSH
Wiley-Interscience series in mass spectrometry
xv, 311 s. : il., tab. ; 25 cm
- MeSH
- fyziologie buňky MeSH
- genomika metody MeSH
- metabolismus MeSH
- systémová biologie metody MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biochemie
- MeSH
- adipokiny genetika klasifikace metabolismus MeSH
- financování organizované MeSH
- genetické techniky * využití MeSH
- genetický výzkum MeSH
- genomika metody MeSH
- inzulinová rezistence MeSH
- lidé MeSH
- metabolický syndrom * etiologie genetika MeSH
- modely genetické MeSH
- přenašeč glukosy typ 4 genetika klasifikace metabolismus MeSH
- proteiny CLOCK genetika metabolismus MeSH
- proteiny vázající retinol genetika klasifikace metabolismus MeSH
- systémová biologie * metody trendy MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH