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| 2. |
- Ali, Muhammad Akhtar, et al.
(författare)
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Molecular pathways in tumor progression : from discovery to functional understanding
- 2009
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Ingår i: Molecular bioSystems. - : Royal Society of Chemistry (RSC). - 1742-206X .- 1742-2051. ; 5:9, s. 902-908
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Forskningsöversikt (refereegranskat)abstract
- The advent of large scale sequencing methods has enabled analyses of the protein-coding parts of cancer genomes to find the mutated genes that cause common human cancers. Unbiased mutation analyses of human tumors originating in the breast, colon, brain, and pancreas have revealed genomic landscapes composed of a few frequently mutated genes alongside a multitude of infrequently mutated genes. These analyses have revealed a stark heterogeneity in the compendium of mutated genes even among tumors of the same tissue origin, and provide evidence for a larger number of driver mutations during tumorigenesis than hitherto presumed. From the multitude of mutated genes, a limited number of central molecular pathways are emerging. Systems biology approaches will be increasingly important to identify and better define these core pathways. Downstream of genetic analyses, scalable methods for prediction and experimental determination of the phenotypes of mutant alleles and pathways will be instrumental for improved mechanistic understanding of cancer as well as future drug discovery efforts.
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| 3. |
- Dell'Orco, Daniele, et al.
(författare)
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Network-level analysis of light adaptation in rod cells under normal and altered conditions
- 2009
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Ingår i: Molecular BioSystems. - : Royal Society of Chemistry (RSC). - 1742-2051 .- 1742-206X. ; 5:10, s. 1232-1246
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Tidskriftsartikel (refereegranskat)abstract
- Photoreceptor cells finely adjust their sensitivity and electrical response according to changes in light stimuli as a direct consequence of the feedback and regulation mechanisms in the phototransduction cascade. In this study, we employed a systems biology approach to develop a dynamic model of vertebrate rod phototransduction that accounts for the details of the underlying biochemistry. Following a bottom-up strategy, we first reproduced the results of a robust model developed by Hamer et al. (Vis. Neurosci., 2005, 22(4), 417), and then added a number of additional cascade reactions including: (a) explicit reactions to simulate the interaction between the activated effector and the regulator of G-protein signalling (RGS); (b) a reaction for the reformation of the G-protein from separate subunits; (c) a reaction for rhodopsin (R) reconstitution from the association of the opsin apoprotein with the 11-cis-retinal chromophore; (d) reactions for the slow activation of the cascade by opsin. The extended network structure successfully reproduced a number of experimental conditions that were inaccessible to prior models. With a single set of parameters the model was able to predict qualitative and quantitative features of rod photoresponses to light stimuli ranging over five orders of magnitude, in normal and altered conditions, including genetic manipulations of the cascade components. In particular, the model reproduced the salient dynamic features of the rod from Rpe65(-/-) animals, a well established model for Leber congenital amaurosis and vitamin A deficiency. The results of this study suggest that a systems-level approach can help to unravel the adaptation mechanisms in normal and in disease-associated conditions on a molecular basis.
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| 4. |
- Gopalacharyulu, Peddinti V., et al.
(författare)
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Dynamic network topology changes in functional modules predict responses to oxidative stress in yeast
- 2009
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Ingår i: Molecular Biosystems. - : Royal Society of Chemistry. - 1742-206X .- 1742-2051. ; 5:3, s. 276-287
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Tidskriftsartikel (refereegranskat)abstract
- In response to environmental challenges, biological systems respond with dynamic adaptive changes in order to maintain the functionality of the system. Such adaptations may lead to cumulative stress over time, possibly leading to global failure of the system. When studying such systems responses, it is therefore important to understand them in system-wide and dynamic context. Here we hypothesize that dynamic changes in the topology of functional modules of integrated biological networks reflect their activity under specific environmental challenges. We introduce topological enrichment analysis of functional subnetworks (TEAFS), a method for the analysis of integrated molecular profile and interactome data, which we validated by comprehensive metabolomic analysis of dynamic yeast response under oxidative stress. TEAFS identified activation of multiple stress response related mechanisms, such as lipid metabolism and phospholipid biosynthesis. We identified, among others, a fatty acid elongase IFA38 as a hub protein which was absent at all time points under oxidative stress conditions. The deletion mutant of the IFA38 encoding gene is known for the accumulation of ceramides. By applying a comprehensive metabolomic analysis, we confirmed the increased concentrations over time of ceramides and palmitic acid, a precursor of de novo ceramide biosynthesis. Our results imply that the connectivity of the system is being dynamically modulated in response to oxidative stress, progressively leading to the accumulation of (lipo)toxic lipids such as ceramides. Studies of local network topology dynamics can be used to investigate as well as predict the activity of biological processes and the system's responses to environmental challenges and interventions.
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| 5. |
- Li, J J, et al.
(författare)
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Electrophoretic and mass spectrometric strategies for profiling bacterial lipopolysaccharides
- 2005
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Ingår i: MOLECULAR BIOSYSTEMS. - : Royal Society of Chemistry (RSC). - 1742-206X .- 1742-2051. ; 1:1, s. 46-52
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Tidskriftsartikel (refereegranskat)abstract
- Capillary electrophoresis (CE) is a high-resolution separation technique that has been widely used for trace analysis in biological samples. On-line capillary electrophoresis-electro spray mass spectrometry (CE-MS) was developed for the analysis of lipopolysaccharide (LPS) glycoforms from the gram-negative bacteria, Haemophilus influenzae. In this paper, we report on the application of CE-MS to characterize structural differences in O-deacylated LPS samples from H. influenzae strains Rd 11.7 and 375.1. The resolution capability of on-line CE-MS was first demonstrated by analysis of a complex LPS mixture from H. influenzae strain Rd 11.7. This strain contains a mixture of isomeric glycoforms differing in the number and positions of hexose moieties. Sialic acid containing glycoforms were also determined. Structural features of LPS from a lic1 mutant of H. influenzae strain 375 (375.1) were studied using on-line CE-MS/MS. With the separation provided by CE, two isomeric glycoforms differing in the location of phosphoethanolamine substituents were characterized by tandem mass spectrometry.
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| 6. |
- Nordling, Torbjörn E. M., et al.
(författare)
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Deduction of intracellular sub-systems from a topological description of the network
- 2007
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Ingår i: Molecular BioSystems. - : Royal Society of Chemistry (RSC). - 1742-206X .- 1742-2051. ; 3:8, s. 523-529
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Tidskriftsartikel (refereegranskat)abstract
- Non-linear behaviour of biochemical networks, such as intracellular gene, protein or metabolic networks, is commonly represented using graphs of the underlying topology. Nodes represent abundance of molecules and edges interactions between pairs of molecules. These graphs are linear and thus based on an implicit linearization of the kinetic reactions in one or several dynamic modes of the total system. It is common to use data from different sources - experiments conducted under different conditions or even on different species - meaning that the graph will be a superposition of linearizations made in many different modes. The mixing of different modes makes it hard to identify functional modules, that is subsystems that carry out a specific biological function, since the graph will contain many interactions that do not naturally occur at the same time. The ability to establish a boundary between the sub- system and its environment is critical in the definition of a module, contrary to a motif in which only internal interactions count. Identification of functional modules should therefore be done on graphs depicting the mode in which their function is carried out, i.e. graphs that only contain edges representing interactions active in the specific mode. In general, when an interaction between two molecules is established, one should always state the mode of the system in which it is active.
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| 7. |
- Samuelsson, Linda, 1973, et al.
(författare)
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Contributions from metabolomics to fish research
- 2008
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Ingår i: Molecular BioSystems. - : Royal Society of Chemistry (RSC). - 1742-206X .- 1742-2051. ; 4, s. 974-979
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Forskningsöversikt (refereegranskat)
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| 9. |
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| 10. |
- Yetukuri, Laxman, et al.
(författare)
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Informatics and computational strategies for the study of lipids
- 2008
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Ingår i: Molecular Biosystems. - : Royal Society of Chemistry. - 1742-206X .- 1742-2051. ; 4:2, s. 121-127
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances in mass spectrometry (MS)-based techniques for lipidomic analysis have empowered us with the tools that afford studies of lipidomes at the systems level. However, these techniques pose a number of challenges for lipidomic raw data processing, lipid informatics, and the interpretation of lipidomic data in the context of lipid function and structure. Integration of lipidomic data with other systemic levels, such as genomic or proteomic, in the context of molecular pathways and biophysical processes provides a basis for the understanding of lipid function at the systems level. The present report, based on the limited literature, is an update on a young but rapidly emerging field of lipid informatics and related pathway reconstruction strategies.
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