Post-translational modifications hugely increase the functional diversity of proteomes. Recent algorithms based on ultratolerant database searching are forging a path to unbiased analysis of peptide modifications by shotgun mass spectrometry. However, these approaches identify only one-half of the modified forms potentially detectable and do not map the modified residue. Moreover, tools for the quantitative analysis of peptide modifications are currently lacking. Here, we present a suite of algorithms that allows comprehensive identification of detectable modifications, pinpoints the modified residues, and enables their quantitative analysis through an integrated statistical model. These developments were used to characterize the impact of mitochondrial heteroplasmy on the proteome and on the modified peptidome in several tissues from 12-week-old mice. Our results reveal that heteroplasmy mainly affects cardiac tissue, inducing oxidative damage to proteins of the oxidative phosphorylation system, and provide a molecular mechanism explaining the structural and functional alterations produced in heart mitochondria.
Audiovisual group communication systems deal with a large number of video streams, and, unlike less advanced videoconferencing systems, require intelligence for selecting adequate views for each of the connected rooms, in order to convey best what is happening in the other locations. Such a decision making component, in our implementation called Orchestration Engine (OE), acts as a Virtual Director. It processes lowlevel events, emitted by content analysis sensors, into editing commands. The OE has two main components: one that semantically lifts low-level events into communication events and one that associates editing decisions to communication contexts. The former has to deal with uncertain and delayed information. The latter subsumes knowledge that reflects both conversation and narrative principles. Both components include contradicting bodies of knowledge. We investigate a rule-based event processing approach and reflect the scalability of our solution regarding competing and contradicting rules.Index Termsvirtual director, semantic abstraction, decision making, rule-based behavior, videoconferencing 2012 IEEE International Conference on Multimedia and Expo Workshops 978-0-7695-4729-9/12 $26.00
17Post-translational modifications hugely increase the functional diversity of 18 proteomes. Recent algorithms based on ultratolerant database searching are 19 forging a path to unbiased analysis of peptide modifications by shotgun mass 20 spectrometry. However, these approaches identify only half of the modified forms 21 potentially detectable and do not map the modified residue. Moreover, tools for the 22 quantitative analysis of peptide modifications are currently lacking. Here, we 23 present a suite of algorithms that allow comprehensive identification of detectable 24 modifications, pinpoint the modified residues, and enable their quantitative 25 analysis through an integrated statistical model. These developments were used to 26 characterize the impact of mitochondrial heteroplasmy on the proteome and on the 27 modified peptidome in several tissues from 12-week old mice. Our results reveal 28 that heteroplasmy mainly affects cardiac tissue, inducing oxidative damage to 29 proteins of the oxidative phosphorylation system, and provide a molecular 30 mechanism that explains the structural and functional alterations produced in 31 heart mitochondria. 32 33 36 Highlights: 37• Identifies all protein modifications detectable by mass spectrometry 38• Locates the modified site with 85% accuracy 39• Integrates quantitative analysis of the proteome and the modified peptidome 40 5 peptide maps can be obtained including practically all the modifications potentially 77 detectable by MS and closed database searches. Our approach also allows accurate 78 location of the modified residues and quantitative analysis of PTMs in the context of 79 proteome-wide studies. We demonstrate the performance of the new tools by 80 performing a comprehensive, tissue-specific characterization of PTMs that are induced 81 by mitochondrial heteroplasmy in a mouse model. Heteroplasmy is a situation that has 82 recently attracted the attention of the biomedical community because it may be 83 produced during mitochondrial replacement therapies aimed to prevent transmission of 84 pathogenic mutations in mitochondrial DNA (Craven et al., 2010) or to treat infertility 85 (Wolf et al., 2015). Mitochondrial heteroplasmy in mice can be genetically unstable and 86 produce adverse physiological effects (Sharpley et al., 2012). The exact molecular 87 mechanisms that produce the pathological effects are unclear and the potential health 88 risk produced by heteroplasmy in the offspring is still a matter under debate. Our results 89show that heteroplasmy between non-pathological mitochondrial DNA variants induces 90 an array of oxidative modifications in heart that are concentrated in proteins belonging 91 to the oxidative phosphorylation system. The new tools thus improve our ability to 92 interpret the totality of information present in MS/MS datasets and provide new 93 proteome-wide perspectives for systems biology analysis in high throughput 94 proteomics. 95 96 RESULTS 97 Comet-PTM enables comprehensive identification of peptide modifications 98We dev...
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