| 1. |
- Carreras-Puigvert, Jordi, et al.
(författare)
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A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family
- 2017
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes. To a certain extent, their substrate preference redundancies correlate with structural classes, thus linking structure and activity relationships. To elucidate interdependence among the NUDIX hydrolases, we pairwise deplete them generating an epistatic interaction map, evaluate cell cycle perturbations upon knockdown in normal and cancer cells, and analyse their protein and mRNA expression in normal and cancer tissues. Using a novel FUSION algorithm, we integrate all data creating a comprehensive NUDIX enzyme profile map, which will prove fundamental to understanding their biological functionality.
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| 2. |
- Danielsson, Frida, et al.
(författare)
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RNA Deep Sequencing as a Tool for Selection of Cell Lines for Systematic Subcellular Localization of All Human Proteins
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:1, s. 231-239
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Tidskriftsartikel (refereegranskat)abstract
- One of the major challenges of a chromosome-centric proteome project is to explore in a systematic manner the potential proteins identified from the chromosomal genome sequence, but not yet characterized on a protein level. Here, we describe the use of RNA deep sequencing to screen human cell lines for RNA profiles and to use this information to select cell lines suitable for characterization of the corresponding gene product. In this manner, the subcellular localization of proteins can be analyzed systematically using antibody-based confocal microscopy. We demonstrate the usefulness of selecting cell lines with high expression levels of RNA transcripts to increase the likelihood of high quality immunofluorescence staining and subsequent successful subcellular localization of the corresponding protein. The results show a path to combine transcriptomics with affinity proteomics to characterize the proteins in a gene- or chromosome-centric manner.
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| 3. |
- Guala, Dimitri, et al.
(författare)
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Experimental validation of predicted cancer genes using FRET
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Huge amounts of data are generated in genome wide experiments, designed to investigatediseases with complex genetic causes. Follow up of all potential leads produced by suchexperiments is currently cost prohibitive and time consuming. Gene prioritization toolsalleviate these constraints by directing further experimental efforts towards the mostpromising candidate targets. Recently a gene prioritization tool called MaxLink was shown tooutperform other widely used state-of-the-art prioritization tools in a large scale in silicobenchmark. An experimental validation of predictions made by MaxLink has however beenlacking. In this study we used Fluorescent Resonance Energy Transfer, an establishedexperimental technique for detection of protein-protein interactions, to validate potentialcancer genes predicted by MaxLink. Our results provide confidence in the use of MaxLink forselection of new targets in the battle with polygenic diseases.
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| 4. |
- Guala, Dimitri, et al.
(författare)
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Experimental validation of predicted cancer genes using FRET
- 2018
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Ingår i: METHODS AND APPLICATIONS IN FLUORESCENCE. - : IOP PUBLISHING LTD. - 2050-6120. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- Huge amounts of data are generated in genome wide experiments, designed to investigate diseases with complex genetic causes. Follow up of all potential leads produced by such experiments is currently cost prohibitive and time consuming. Gene prioritization tools alleviate these constraints by directing further experimental efforts towards the most promising candidate targets. Recently a gene prioritization tool called MaxLink was shown to outperform other widely used state-of-the-art prioritization tools in a large scale in silico benchmark. An experimental validation of predictions made by MaxLink has however been lacking. In this study we used Fluorescence Resonance Energy Transfer, an established experimental technique for detection of protein-protein interactions, to validate potential cancer genes predicted by MaxLink. Our results provide confidence in the use of MaxLink for selection of new targets in the battle with polygenic diseases.
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| 5. |
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| 6. |
- Thul, Peter J., et al.
(författare)
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A subcellular map of the human proteome
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 356:6340
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Tidskriftsartikel (refereegranskat)abstract
- Resolving the spatial distribution of the human proteome at a subcellular level can greatly increase our understanding of human biology and disease. Here we present a comprehensive image-based map of subcellular protein distribution, the Cell Atlas, built by integrating transcriptomics and antibody-based immunofluorescence microscopy with validation by mass spectrometry. Mapping the in situ localization of 12,003 human proteins at a single-cell level to 30 subcellular structures enabled the definition of the proteomes of 13 major organelles. Exploration of the proteomes revealed single-cell variations in abundance or spatial distribution and localization of about half of the proteins to multiple compartments. This subcellular map can be used to refine existing protein-protein interaction networks and provides an important resource to deconvolute the highly complex architecture of the human cell.
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| 7. |
- Wiking, Mikaela, et al.
(författare)
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The Subcellular Protein Atlas
- 2014
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Ingår i: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 25
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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