{"entity": "label", "iuid": "af20d91863004a918a960934c76c4630", "timestamp": "2026-07-14T01:15:58.379Z", "links": {"self": {"href": "https://publications.scilifelab.se/label/Clinical%20Proteomics%20Mass%20spectrometry.json"}, "display": {"href": "https://publications.scilifelab.se/label/Clinical%20Proteomics%20Mass%20spectrometry"}}, "value": "Clinical Proteomics Mass spectrometry", "started": "2013", "ended": "2016", "created": "2017-05-03T12:51:58.218Z", "modified": "2021-03-15T14:17:55.629Z", "accounts": [{"entity": "account", "iuid": "32a436398938412b93e7ddcef018c708", "timestamp": "2026-07-14T01:15:58.379Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/christopher.erdmann%40scilifelab.uu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/christopher.erdmann%40scilifelab.uu.se"}}, "email": "christopher.erdmann@scilifelab.uu.se", "name": "Christopher Erdmann", "orcid": "", "role": "curator", "status": "enabled", "login": "2024-08-16T11:56:57.787Z", "created": "2024-08-16T10:01:32.844Z", "modified": "2025-10-17T13:05:06.782Z"}, {"entity": "account", "iuid": "6a38350bd21f4fb6aeeb1530037a99ae", "timestamp": "2026-07-14T01:15:58.379Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/sune.joubert%40scilifelab.uu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/sune.joubert%40scilifelab.uu.se"}}, "email": "sune.joubert@scilifelab.uu.se", "name": "Sun\u00e9 Joubert", "orcid": "", "role": "curator", "status": "enabled", "login": "2025-10-31T11:15:37.113Z", "created": "2024-08-16T10:01:02.800Z", "modified": "2025-10-31T11:15:37.113Z"}, {"entity": "account", "iuid": "de9e085deec3415cb87169898b721399", "timestamp": "2026-07-14T01:15:58.379Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/janne.lehtio%40ki.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/janne.lehtio%40ki.se"}}, "email": "janne.lehtio@ki.se", "name": "Janne Lehti\u00f6", "orcid": null, "role": "curator", "status": "enabled", "login": "2017-12-05T10:05:54.769Z", "created": "2017-05-03T12:52:05.698Z", "modified": "2021-03-05T08:29:38.049Z"}], "publications_count": 25, "publications": [{"entity": "publication", "iuid": "e66120f3f3b04764beb8e0005b69df33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e66120f3f3b04764beb8e0005b69df33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e66120f3f3b04764beb8e0005b69df33"}}, "title": "Molecular profiles of oxyphilic and chief cell parathyroid adenoma.", "authors": [{"family": "Lu", "given": "Ming", "initials": "M"}, {"family": "Kjellin", "given": "Hanna", "initials": "H"}, {"family": "Fotouhi", "given": "Omid", "initials": "O"}, {"family": "Lee", "given": "Linkiat", "initials": "L"}, {"family": "Nilsson", "given": "Inga-Lena", "initials": "IL"}, {"family": "Haglund", "given": "Felix", "initials": "F"}, {"family": "H\u00f6\u00f6g", "given": "Anders", "initials": "A"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Larsson", "given": "Catharina", "initials": "C"}], "type": "journal article", "published": "2018-07-15", "journal": {"volume": "470", "issn": "1872-8057", "issue": null, "title": "Mol. Cell. Endocrinol.", "pages": "84-95", "issn-l": "0303-7207"}, "abstract": "Parathyroid adenomas may be composed of chief cells (conventional or water-clear), oxyphilic cells or a mixture of both cells. The molecular background is rarely studied.\n\nTo molecularly characterize parathyroid adenomas of different cell type composition.\n\nChief and oxyphilic cell adenomas were compared in a cohort of 664 sporadic cases. Extensive analyses of parathyroid tissues were performed in subgroup. Gene expressions of known parathyroid-related genes were quantified by qRT-PCR. Protein expression profiles determined by liquid chromatography - tandem mass spectrometry (LC-MS/MS) were compared between each type of parathyroid adenomas. Selected proteins were analysed by Western blot and immunohistochemistry.\n\nPatients with oxyphilic cell adenoma were found to be older at the time of operation than chief cell adenoma cases but did not differ in gender, serum calcium or tumor weight. The gene expression of CASR, VDR, FGFR1, CYP27B1, CYP24A1, PTHLH, GCM2, NDUFA13, CDKN1B, MEN1 and CNND1 did not differ between the groups. VDR protein levels were weaker in oxyphilic adenomas. The proteomic studies identified a set of novel dysregulated proteins of interest such as nuclear receptor subfamily 2 group C member 2 (TR4), LIM domain only protein 3 (LMO3) and calcium-binding protein B (S100B). LMO3 and S100B showed higher expression in oxyphilic adenoma and may be involve in parathyroid tumorgenesis through the p53 pathway. TR4 showed different subcellular localisation between adenoma and normal rim.\n\nChief and oxyphilic cell parathyroid adenomas have partly overlapping but also distinct molecular profiles. The calmodulin-eEF2K, TR4 and p53 pathways may be involved in the tumor development.", "doi": "10.1016/j.mce.2017.10.001", "pmid": "28986304", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0303-7207(17)30521-X"}], "notes": [], "created": "2017-12-05T16:14:24.861Z", "modified": "2021-07-08T11:36:15.292Z"}, {"entity": "publication", "iuid": "ee6612f009784d75bef6f813135621b2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee6612f009784d75bef6f813135621b2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee6612f009784d75bef6f813135621b2"}}, "title": "A Common Peptidolytic Mechanism for Targeting Peptide Degradation in Mitochondria and Chloroplasts.", "authors": [{"family": "Kmiec", "given": "Beata", "initials": "B"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Murcha", "given": "Monika W", "initials": "MW"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Glaser", "given": "Elzbieta", "initials": "E"}, {"family": "Teixeira", "given": "Pedro F", "initials": "PF"}], "type": "letter", "published": "2018-02-05", "journal": {"title": "Mol Plant", "issn": "1752-9867", "issn-l": "1674-2052", "volume": "11", "issue": "2", "pages": "342-345"}, "abstract": null, "doi": "10.1016/j.molp.2017.11.008", "pmid": "29183773", "labels": {"Global Proteomics and Proteogenomics": "Service", "Clinical Proteomics Mass spectrometry": "Service", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "S1674-2052(17)30342-8"}], "notes": [], "created": "2018-10-31T07:12:33.028Z", "modified": "2025-10-17T13:03:18.311Z"}, {"entity": "publication", "iuid": "3c9517923fd04189a047817e54cbdc2f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c9517923fd04189a047817e54cbdc2f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c9517923fd04189a047817e54cbdc2f"}}, "title": "Mechanism of Peptide Binding and Cleavage by the Human Mitochondrial Peptidase Neurolysin.", "authors": [{"family": "Teixeira", "given": "Pedro F", "initials": "PF"}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G"}, {"family": "Pinho", "given": "Catarina M", "initials": "CM"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Kmiec", "given": "Beata", "initials": "B"}, {"family": "Wallin", "given": "Cecilia", "initials": "C"}, {"family": "W\u00e4rml\u00e4nder", "given": "Sebastian K T S", "initials": "SKTS"}, {"family": "Berntsson", "given": "Ronnie P-A", "initials": "RP"}, {"family": "Ankarcrona", "given": "Maria", "initials": "M"}, {"family": "Gr\u00e4slund", "given": "Astrid", "initials": "A"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P"}, {"family": "Glaser", "given": "Elzbieta", "initials": "E"}], "type": "journal article", "published": "2018-02-02", "journal": {"volume": "430", "issn": "1089-8638", "issue": "3", "title": "J. Mol. Biol.", "pages": "348-362", "issn-l": "0022-2836"}, "abstract": "Proteolysis plays an important role in mitochondrial biogenesis, from the processing of newly imported precursor proteins to the degradation of mitochondrial targeting peptides. Disruption of peptide degradation activity in yeast, plant and mammalian mitochondria is known to have deleterious consequences for organism physiology, highlighting the important role of mitochondrial peptidases. In the present work, we show that the human mitochondrial peptidase neurolysin (hNLN) can degrade mitochondrial presequence peptides as well as other fragments up to 19 amino acids long. The crystal structure of hNLNE475Q in complex with the products of neurotensin cleavage at 2.7\u00c5 revealed a closed conformation with an internal cavity that restricts substrate length and highlighted the mechanism of enzyme opening/closing that is necessary for substrate binding and catalytic activity. Analysis of peptide degradation in vitro showed that hNLN cooperates with presequence protease (PreP or PITRM1) in the degradation of long targeting peptides and amyloid-\u03b2 peptide, A\u03b21-40, associated with Alzheimer disease, particularly cleaving the hydrophobic fragment A\u03b235-40. These findings suggest that a network of proteases may be required for complete degradation of peptides localized in mitochondria.", "doi": "10.1016/j.jmb.2017.11.011", "pmid": "29183787", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0022-2836(17)30561-2"}], "notes": [], "created": "2017-12-05T16:12:35.308Z", "modified": "2021-07-08T11:36:15.178Z"}, {"entity": "publication", "iuid": "f08e80cf3ad947d6b39ed822df64d201", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f08e80cf3ad947d6b39ed822df64d201.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f08e80cf3ad947d6b39ed822df64d201"}}, "title": "Normalization of mass spectrometry data (NOMAD).", "authors": [{"family": "Murie", "given": "Carl", "initials": "C"}, {"family": "Sandri", "given": "Brian", "initials": "B"}, {"family": "Sandberg", "given": "Ann-Sofi", "initials": "AS", "orcid": "0000-0002-9681-3342", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd34d8e107be4a87b60c8dc525277463.json"}}, {"family": "Griffin", "given": "Timothy J", "initials": "TJ"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Wendt", "given": "Christine", "initials": "C"}, {"family": "Larsson", "given": "Ola", "initials": "O"}], "type": "journal article", "published": "2018-01-00", "journal": {"volume": "67", "issn": "2212-4934", "issue": null, "title": "Adv Biol Regul", "pages": "128-133", "issn-l": "2212-4926"}, "abstract": "iTRAQ and TMT reagent-based mass spectrometry (MS) are commonly used technologies for quantitative proteomics in biological samples. Such studies are often performed over multiple MS runs, potentially resulting in introduction of MS run bias that could affect downstream analysis. Such MS data have therefore commonly been normalized using a reference sample which is included in each MS run. We show, however, that reference normalization does not effectively remove systematic MS run bias. A linear model approach was previously proposed to improve on the reference normalization approach but does not computationally scale to larger data sets. Here we describe the NOMAD (normalization of mass spectrometry data) R package which implements a computationally efficient ANOVA normalization approach with protein assembly functionality. NOMAD provides the same advantages as the linear regression solution but is more computationally efficient which allows superior scaling to larger sample sizes. Moreover, NOMAD effectively removes bias which improves valid across MS run comparisons.", "doi": "10.1016/j.jbior.2017.11.005", "pmid": "29174395", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "S2212-4926(17)30174-4"}, {"db": "pmc", "key": "PMC5885284"}, {"db": "mid", "key": "NIHMS951780"}], "notes": [], "created": "2017-12-05T16:14:22.060Z", "modified": "2023-06-19T12:54:45.273Z"}, {"entity": "publication", "iuid": "322d19d8a8f24583bfce02ae7f8a2aa2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/322d19d8a8f24583bfce02ae7f8a2aa2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/322d19d8a8f24583bfce02ae7f8a2aa2"}}, "title": "Female mice lacking Pald1 exhibit endothelial cell apoptosis and emphysema.", "authors": [{"family": "Ega\u00f1a", "given": "Isabel", "initials": "I"}, {"family": "Kaito", "given": "Hiroshi", "initials": "H"}, {"family": "Nitzsche", "given": "Anja", "initials": "A"}, {"family": "Becker", "given": "Lore", "initials": "L"}, {"family": "Ballester-Lopez", "given": "Carolina", "initials": "C"}, {"family": "Niaudet", "given": "Colin", "initials": "C"}, {"family": "Petkova", "given": "Milena", "initials": "M"}, {"family": "Liu", "given": "Wei", "initials": "W"}, {"family": "Vanlandewijck", "given": "Michael", "initials": "M"}, {"family": "Vernaleken", "given": "Alexandra", "initials": "A"}, {"family": "Klopstock", "given": "Thomas", "initials": "T"}, {"family": "Fuchs", "given": "Helmut", "initials": "H"}, {"family": "Gailus-Durner", "given": "Valerie", "initials": "V"}, {"family": "Hrabe de Angelis", "given": "Martin", "initials": "M"}, {"family": "Rask-Andersen", "given": "Helge", "initials": "H"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "He", "given": "Liqun", "initials": "L"}, {"family": "Yildirim", "given": "Ali \u00d6", "initials": "A\u00d6"}, {"family": "Hellstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "German Mouse Clinic Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2017-11-13", "journal": {"volume": "7", "issn": "2045-2322", "issue": "1", "pages": "15453", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Paladin (Pald1, mKIAA1274 or x99384) was identified in screens for vascular-specific genes and is a putative phosphatase. Paladin has also been proposed to be involved in various biological processes such as insulin signaling, innate immunity and neural crest migration. To determine the role of paladin we have now characterized the Pald1 knock-out mouse in a broad array of behavioral, physiological and biochemical tests. Here, we show that female, but not male, Pald1 heterozygous and homozygous knock-out mice display an emphysema-like histology with increased alveolar air spaces and impaired lung function with an obstructive phenotype. In contrast to many other tissues where Pald1 is restricted to the vascular compartment, Pald1 is expressed in both the epithelial and mesenchymal compartments of the postnatal lung. However, in Pald1 knock-out females, there is a specific increase in apoptosis and proliferation of endothelial cells, but not in non-endothelial cells. This results in a transient reduction of endothelial cells in the maturing lung. Our data suggests that Pald1 is required during lung vascular development and for normal function of the developing and adult lung in a sex-specific manner. To our knowledge, this is the first report of a sex-specific effect on endothelial cell apoptosis.", "doi": "10.1038/s41598-017-14894-9", "pmid": "29133847", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-017-14894-9"}, {"db": "pmc", "key": "PMC5684320"}], "notes": [], "created": "2017-12-05T16:14:22.822Z", "modified": "2021-07-08T11:36:15.159Z"}, {"entity": "publication", "iuid": "60b0d98d513c4af988e4c92ae49decbd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/60b0d98d513c4af988e4c92ae49decbd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/60b0d98d513c4af988e4c92ae49decbd"}}, "title": "Identification of the PAK4 interactome reveals PAK4 phosphorylation of N-WASP and promotion of Arp2/3-dependent actin polymerization.", "authors": [{"family": "Zhao", "given": "Miao", "initials": "M"}, {"family": "Spiess", "given": "Matthias", "initials": "M"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Olofsson", "given": "Helene", "initials": "H"}, {"family": "Hu", "given": "Jianjiang", "initials": "J"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Str\u00f6mblad", "given": "Staffan", "initials": "S"}], "type": "journal article", "published": "2017-09-29", "journal": {"volume": "8", "issn": "1949-2553", "issue": "44", "pages": "77061-77074", "title": "Oncotarget", "issn-l": "1949-2553"}, "abstract": "p21-activated kinase 4 (PAK4) regulates cell proliferation, apoptosis, cell motility and F-actin remodeling, but the PAK4 interactome has not been systematically analyzed. Here, we comprehensively characterized the human PAK4 interactome by iTRAQ quantitative mass spectrometry of PAK4-immunoprecipitations. Consistent with its multiple reported functions, the PAK4 interactome was enriched in diverse protein networks, including the 14-3-3, proteasome, replication fork, CCT and Arp2/3 complexes. Because PAK4 co-immunoprecipitated most subunits of the Arp2/3 complex, we hypothesized that PAK4 may play a role in Arp2/3 dependent actin regulation. Indeed, we found that PAK4 interacts with and phosphorylates the nucleation promoting factor N-WASP at Ser484/Ser485 and promotes Arp2/3-dependent actin polymerization in vitro. Also, PAK4 ablation in vivo reduced N-WASP Ser484/Ser485 phosphorylation and altered the cellular balance between G- and F-actin as well as the actin organization. By presenting the PAK4 interactome, we here provide a powerful resource for further investigations and as proof of principle, we also indicate a novel mechanism by which PAK4 regulates actin cytoskeleton remodeling.", "doi": "10.18632/oncotarget.20352", "pmid": "29100370", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "20352"}, {"db": "pmc", "key": "PMC5652764"}], "notes": [], "created": "2017-12-05T16:14:23.542Z", "modified": "2021-07-08T11:36:15.220Z"}, {"entity": "publication", "iuid": "d1e74ad1e3134682be2aa625c2c3d42f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d1e74ad1e3134682be2aa625c2c3d42f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d1e74ad1e3134682be2aa625c2c3d42f"}}, "title": "Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes metastasis-related properties via TGF\u03b22/T\u03b2R and CD44 in MDA-MB-231 breast cancer cells.", "authors": [{"family": "Reithmeier", "given": "Anja", "initials": "A"}, {"family": "Panizza", "given": "Elena", "initials": "E"}, {"family": "Krumpel", "given": "Michael", "initials": "M"}, {"family": "Orre", "given": "Lukas M", "initials": "LM"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Ek-Rylander", "given": "Barbro", "initials": "B"}, {"family": "Andersson", "given": "G\u00f6ran", "initials": "G"}], "type": "journal article", "published": "2017-09-15", "journal": {"volume": "17", "issn": "1471-2407", "issue": "1", "pages": "650", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness.\n\nMDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels. Functional cell experiments, such as proliferation, migration and invasion assays were performed as well as global phosphoproteomic and proteomic analysis was conducted to connect molecular perturbations to the phenotypic changes.\n\nWe identified an association between metastasis-related properties of TRAP-overexpressing MDA-MB-231 breast cancer cells and a TRAP-dependent regulation of Transforming growth factor (TGF\u03b2) pathway proteins and Cluster of differentiation 44 (CD44). Overexpression of TRAP increased anchorage-independent and anchorage-dependent cell growth and proliferation, induced a more elongated cellular morphology and promoted cell migration and invasion. Migration was increased in the presence of the extracellular matrix (ECM) proteins osteopontin and fibronectin and the basement membrane proteins collagen IV and laminin I. TRAP-induced properties were reverted upon shRNA-mediated knockdown of TRAP or treatment with the small molecule TRAP inhibitor 5-PNA. Global phosphoproteomics and proteomics analyses identified possible substrates of TRAP phosphatase activity or signaling intermediates and outlined a TRAP-dependent regulation of proteins involved in cell adhesion and ECM organization. Upregulation of TGF\u03b2 isoform 2 (TGF\u03b22), TGF\u03b2 receptor type 1 (T\u03b2R1) and Mothers against decapentaplegic homolog 2 (SMAD2), as well as increased intracellular phosphorylation of CD44 were identified upon TRAP perturbation. Functional antibody-mediated blocking and chemical inhibition demonstrated that TRAP-dependent migration and proliferation is regulated via TGF\u03b22/T\u03b2R, whereas proliferation beyond basal levels is regulated through CD44.\n\nAltogether, TRAP promotes metastasis-related cell properties in MDA-MB-231 breast cancer cells via TGF\u03b22/T\u03b2R and CD44, thereby identifying a potential signaling mechanism associated to TRAP action in breast cancer cells.", "doi": "10.1186/s12885-017-3616-7", "pmid": "28915803", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-017-3616-7"}, {"db": "pmc", "key": "PMC5602878"}], "notes": [], "created": "2017-12-05T16:14:25.657Z", "modified": "2021-07-08T11:36:15.281Z"}, {"entity": "publication", "iuid": "481f7584fddd4db2a5d9f3833a7ed7e8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/481f7584fddd4db2a5d9f3833a7ed7e8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/481f7584fddd4db2a5d9f3833a7ed7e8"}}, "title": "Silencing FLI or targeting CD13/ANPEP lead to dephosphorylation of EPHA2, a mediator of BRAF inhibitor resistance, and induce growth arrest or apoptosis in melanoma cells.", "authors": [{"family": "Azimi", "given": "Alireza", "initials": "A"}, {"family": "Tuominen", "given": "Rainer", "initials": "R"}, {"family": "Costa Svedman", "given": "Fernanda", "initials": "F"}, {"family": "Caramuta", "given": "Stefano", "initials": "S"}, {"family": "Pernemalm", "given": "Maria", "initials": "M", "orcid": "0000-0003-4624-031X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f15f303cb2044cfa81719700137e3603.json"}}, {"family": "Frostvik Stolt", "given": "Marianne", "initials": "M"}, {"family": "Kanter", "given": "Lena", "initials": "L"}, {"family": "Kharaziha", "given": "Pedram", "initials": "P"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Hertzman Johansson", "given": "Carolina", "initials": "C"}, {"family": "H\u00f6iom", "given": "Veronica", "initials": "V"}, {"family": "Hansson", "given": "Johan", "initials": "J"}, {"family": "Egyhazi Brage", "given": "Suzanne", "initials": "S", "orcid": "0000-0002-0524-2346", "researcher": {"href": "https://publications.scilifelab.se/researcher/40eddeacb66f490089dbf72978d20721.json"}}], "type": "journal article", "published": "2017-08-31", "journal": {"volume": "8", "issn": "2041-4889", "issue": "8", "pages": "e3029", "title": "Cell Death Dis", "issn-l": "2041-4889"}, "abstract": "A majority of patients with BRAF-mutated metastatic melanoma respond to therapy with BRAF inhibitors (BRAFi), but relapses are common owing to acquired resistance. To unravel BRAFi resistance mechanisms we have performed gene expression and mass spectrometry based proteome profiling of the sensitive parental A375 BRAF V600E-mutated human melanoma cell line and of daughter cell lines with induced BRAFi resistance. Increased expression of two novel resistance candidates, aminopeptidase-N (CD13/ANPEP) and ETS transcription factor FLI1 was observed in the BRAFi-resistant daughter cell lines. In addition, increased levels of the previously reported resistance mediators, receptor tyrosine kinase ephrine receptor A2 (EPHA2) and the hepatocyte growth factor receptor MET were also identified. The expression of these proteins was assessed in matched tumor samples from melanoma patients obtained before BRAFi and after disease progression. MET was overexpressed in all progression samples while the expression of the other candidates varied between the individual patients. Targeting CD13/ANPEP by a blocking antibody induced apoptosis in both parental A375- and BRAFi-resistant daughter cells as well as in melanoma cells with intrinsic BRAFi resistance and led to dephosphorylation of EPHA2 on S897, previously demonstrated to cause inhibition of the migratory capacity. AKT and RSK, both reported to induce EPHA2 S897 phosphorylation, were also dephosphorylated after inhibition of CD13/ANPEP. FLI1 silencing also caused decreases in EPHA2 S897 phosphorylation and in total MET protein expression. In addition, silencing of FLI1 sensitized the resistant cells to BRAFi. Furthermore, we show that BRAFi in combination with the multi kinase inhibitor dasatinib can abrogate BRAFi resistance and decrease both EPHA2 S897 phosphorylation and total FLI1 protein expression. This is the first report presenting CD13/ANPEP and FLI1 as important mediators of resistance to BRAF inhibition with potential as drug targets in BRAFi refractory melanoma.", "doi": "10.1038/cddis.2017.406", "pmid": "29048432", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "Clinical Proteomics Mass spectrometry": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "cddis2017406"}, {"db": "pmc", "key": "PMC5596587"}], "notes": [], "created": "2017-10-17T07:53:20.719Z", "modified": "2021-07-08T11:36:54.639Z"}, {"entity": "publication", "iuid": "a782b516dd7b4b838b69f46f09a13e7d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a782b516dd7b4b838b69f46f09a13e7d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a782b516dd7b4b838b69f46f09a13e7d"}}, "title": "Tuning Metabolome Coverage in Reversed Phase LC-MS Metabolomics of MeOH Extracted Samples Using the Reconstitution Solvent Composition.", "authors": [{"family": "Lindahl", "given": "Anna", "initials": "A"}, {"family": "S\u00e4\u00e4f", "given": "Siv", "initials": "S"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Nordstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0003-3676-817X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b1803a3f7624f0d82abd552448bdaed.json"}}], "type": "journal article", "published": "2017-07-18", "journal": {"volume": "89", "issn": "1520-6882", "issue": "14", "pages": "7356-7364", "title": "Anal. Chem.", "issn-l": "0003-2700"}, "abstract": "Considering the physicochemical diversity of the metabolome, untargeted metabolomics will inevitably discriminate against certain compound classes. Efforts are nevertheless made to maximize the metabolome coverage. Contrary to the main steps of a typical liquid chromatography-mass spectrometry (LC-MS) metabolomics workflow, such as metabolite extraction, the sample reconstitution step has not been optimized for maximal metabolome coverage. This sample concentration step typically occurs after metabolite extraction, when dried samples are reconstituted in a solvent for injection on column. The aim of this study was to evaluate the impact of the sample reconstitution solvent composition on metabolome coverage in untargeted LC-MS metabolomics. Lysogeny Broth medium samples reconstituted in MeOH/H 2O ratios ranging from 0 to 100% MeOH and analyzed with untargeted reversed phase LC-MS showed that the highest number of metabolite features (n = 1500) was detected in samples reconstituted in 100% H2O. As compared to a commonly used reconstitution solvent mixture of 50/50 MeOH/H2O, our results indicate that the small fraction of compounds increasing in peak area response by the addition of MeOH to H2O, 5%, is outweighed by the fraction of compounds with decreased response, 57%. We evaluated our results on human serum samples from lymphoma patients and healthy control subjects. Reconstitution in 100% H2O resulted in a higher number of significant metabolites discriminating between these two groups than both 50% and 100% MeOH. These findings show that the sample reconstitution step has a clear impact on the metabolome coverage of MeOH extracted biological samples, highlighting the importance of the reconstitution solvent composition for untargeted discovery metabolomics.", "doi": "10.1021/acs.analchem.7b00475", "pmid": "28613827", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service", "Swedish Metabolomics Centre": "Technology development"}, "xrefs": [], "notes": [], "created": "2017-12-05T16:14:27.211Z", "modified": "2025-10-17T13:03:18.634Z"}, {"entity": "publication", "iuid": "44e0dcce999c41adb598ab8a38a2cc4c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/44e0dcce999c41adb598ab8a38a2cc4c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/44e0dcce999c41adb598ab8a38a2cc4c"}}, "title": "Isoelectric point-based fractionation by HiRIEF coupled to LC-MS allows for in-depth quantitative analysis of the phosphoproteome.", "authors": [{"family": "Panizza", "given": "Elena", "initials": "E"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Oliviusson", "given": "Peter", "initials": "P"}, {"family": "Orre", "given": "Lukas M", "initials": "LM"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2017-07-03", "journal": {"volume": "7", "issn": "2045-2322", "issue": "1", "pages": "4513", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Protein phosphorylation is involved in the regulation of most eukaryotic cells functions and mass spectrometry-based analysis has made major contributions to our understanding of this regulation. However, low abundance of phosphorylated species presents a major challenge in achieving comprehensive phosphoproteome coverage and robust quantification. In this study, we developed a workflow employing titanium dioxide phospho-enrichment coupled with isobaric labeling by Tandem Mass Tags (TMT) and high-resolution isoelectric focusing (HiRIEF) fractionation to perform in-depth quantitative phosphoproteomics starting with a low sample quantity. To benchmark the workflow, we analyzed HeLa cells upon pervanadate treatment or cell cycle arrest in mitosis. Analyzing 300 \u00b5g of peptides per sample, we identified 22,712 phosphorylation sites, of which 19,075 were localized with high confidence and 1,203 are phosphorylated tyrosine residues, representing 6.3% of all detected phospho-sites. HiRIEF fractions with the most acidic isoelectric points are enriched in multiply phosphorylated peptides, which represent 18% of all the phospho-peptides detected in the pH range 2.5-3.7. Cross-referencing with the PhosphoSitePlus database reveals 1,264 phosphorylation sites that have not been previously reported and kinase association analysis suggests that a subset of these may be functional during the mitotic phase.", "doi": "10.1038/s41598-017-04798-z", "pmid": "28674419", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-017-04798-z"}, {"db": "pmc", "key": "PMC5495806"}], "notes": [], "created": "2017-12-05T16:14:26.493Z", "modified": "2021-07-08T11:36:15.117Z"}, {"entity": "publication", "iuid": "99c4a012bd934c289bd13c457c63189a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/99c4a012bd934c289bd13c457c63189a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/99c4a012bd934c289bd13c457c63189a"}}, "title": "Discrimination of pancreatic cancer and pancreatitis by LC-MS metabolomics.", "authors": [{"family": "Lindahl", "given": "Anna", "initials": "A"}, {"family": "Heuchel", "given": "Rainer", "initials": "R"}, {"family": "Forshed", "given": "Jenny", "initials": "J"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "L\u00f6hr", "given": "Matthias", "initials": "M"}, {"family": "Nordstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0003-3676-817X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b1803a3f7624f0d82abd552448bdaed.json"}}], "type": "journal article", "published": "2017-04-01", "journal": {"volume": "13", "issn": "1573-3882", "issue": "5", "pages": "61", "title": "Metabolomics", "issn-l": null}, "abstract": "Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer-related death in Europe with a 5-year survival rate of <5%. Chronic pancreatitis (CP) is a risk factor for PDAC development, but in the majority of cases malignancy is discovered too late for curative treatment. There is at present no reliable diagnostic marker for PDAC available.\n\nThe aim of the study was to identify single blood-based metabolites or a panel of metabolites discriminating PDAC and CP using liquid chromatography-mass spectrometry (LC-MS).\n\nA discovery cohort comprising PDAC (n = 44) and CP (n = 23) samples was analyzed by LC-MS followed by univariate (Student's t test) and multivariate (orthogonal partial least squares-discriminant analysis (OPLS-DA)) statistics. Discriminative metabolite features were subject to raw data examination and identification to ensure high feature quality. Their discriminatory power was then confirmed in an independent validation cohort including PDAC (n = 20) and CP (n = 31) samples.\n\nGlycocholic acid, N-palmitoyl glutamic acid and hexanoylcarnitine were identified as single markers discriminating PDAC and CP by univariate analysis. OPLS-DA resulted in a panel of five metabolites including the aforementioned three metabolites as well as phenylacetylglutamine (PAGN) and chenodeoxyglycocholate.\n\nUsing LC-MS-based metabolomics we identified three single metabolites and a five-metabolite panel discriminating PDAC and CP in two independent cohorts. Although further study is needed in larger cohorts, the metabolites identified are potentially of use in PDAC diagnostics.", "doi": "10.1007/s11306-017-1199-6", "pmid": "28413374", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "1199"}, {"db": "pmc", "key": "PMC5376388"}], "notes": [], "created": "2017-12-05T16:14:27.928Z", "modified": "2025-10-17T13:03:18.911Z"}, {"entity": "publication", "iuid": "462837a655434c04a22ffd076f56c646", "links": {"self": {"href": "https://publications.scilifelab.se/publication/462837a655434c04a22ffd076f56c646.json"}, "display": {"href": "https://publications.scilifelab.se/publication/462837a655434c04a22ffd076f56c646"}}, "title": "Proteogenomics produces comprehensive and highly accurate protein-coding gene annotation in a complete genome assembly of Malassezia sympodialis.", "authors": [{"family": "Zhu", "given": "Yafeng", "initials": "Y", "orcid": "0000-0003-1947-9026", "researcher": {"href": "https://publications.scilifelab.se/researcher/d464b30bf5174a8fb456601d75aecb14.json"}}, {"family": "Engstr\u00f6m", "given": "P\u00e4r G", "initials": "PG", "orcid": "0000-0001-5265-2121", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ce330ec225f4a8595932d092ab8c8d1.json"}}, {"family": "Tellgren-Roth", "given": "Christian", "initials": "C"}, {"family": "Baudo", "given": "Charles D", "initials": "CD"}, {"family": "Kennell", "given": "John C", "initials": "JC"}, {"family": "Sun", "given": "Sheng", "initials": "S"}, {"family": "Billmyre", "given": "R Blake", "initials": "RB"}, {"family": "Schr\u00f6der", "given": "Markus S", "initials": "MS"}, {"family": "Andersson", "given": "Anna", "initials": "A"}, {"family": "Holm", "given": "Tina", "initials": "T"}, {"family": "Sigurgeirsson", "given": "Benjamin", "initials": "B"}, {"family": "Wu", "given": "Guangxi", "initials": "G"}, {"family": "Sankaranarayanan", "given": "Sundar Ram", "initials": "SR"}, {"family": "Siddharthan", "given": "Rahul", "initials": "R"}, {"family": "Sanyal", "given": "Kaustuv", "initials": "K"}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Nystedt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-7809-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0af5a168baa4b00a6fab8d3447ebfb4.json"}}, {"family": "Boekhout", "given": "Teun", "initials": "T"}, {"family": "Dawson", "given": "Thomas L", "initials": "TL"}, {"family": "Heitman", "given": "Joseph", "initials": "J"}, {"family": "Scheynius", "given": "Annika", "initials": "A"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2017-03-17", "journal": {"volume": "45", "issn": "1362-4962", "issue": "5", "pages": "2629-2643", "title": "Nucleic Acids Res.", "issn-l": "0305-1048"}, "abstract": "Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotation remains a major challenge. Here, we present a complete genome assembly of the skin commensal yeast Malassezia sympodialis and demonstrate how proteogenomics can substantially improve gene annotation. Through long-read DNA sequencing, we obtained a gap-free genome assembly for M. sympodialis (ATCC 42132), comprising eight nuclear and one mitochondrial chromosome. We also sequenced and assembled four M. sympodialis clinical isolates, and showed their value for understanding Malassezia reproduction by confirming four alternative allele combinations at the two mating-type loci. Importantly, we demonstrated how proteomics data could be readily integrated with transcriptomics data in standard annotation tools. This increased the number of annotated protein-coding genes by 14% (from 3612 to 4113), compared to using transcriptomics evidence alone. Manual curation further increased the number of protein-coding genes by 9% (to 4493). All of these genes have RNA-seq evidence and 87% were confirmed by proteomics. The M. sympodialis genome assembly and annotation presented here is at a quality yet achieved only for a few eukaryotic organisms, and constitutes an important reference for future host-microbe interaction studies.", "doi": "10.1093/nar/gkx006", "pmid": "28100699", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "Clinical Proteomics Mass spectrometry": "Technology development", "National Genomics Infrastructure": "Collaborative", "Global Proteomics and Proteogenomics": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "gkx006"}, {"db": "pmc", "key": "PMC5389616"}], "notes": [], "created": "2017-08-23T14:28:34.856Z", "modified": "2024-01-16T13:48:48.270Z"}, {"entity": "publication", "iuid": "37442ab98d914bb1827ce6b803dae200", "links": {"self": {"href": "https://publications.scilifelab.se/publication/37442ab98d914bb1827ce6b803dae200.json"}, "display": {"href": "https://publications.scilifelab.se/publication/37442ab98d914bb1827ce6b803dae200"}}, "title": "A multi-step peptidolytic cascade for amino acid recovery in chloroplasts.", "authors": [{"family": "Teixeira", "given": "Pedro F", "initials": "PF", "orcid": "0000-0001-8638-7477", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b43730fe20b424db84f091333be7244.json"}}, {"family": "Kmiec", "given": "Beata", "initials": "B"}, {"family": "Branca", "given": "Rui M M", "initials": "RM"}, {"family": "Murcha", "given": "Monika W", "initials": "MW", "orcid": "0000-0002-3689-6158", "researcher": {"href": "https://publications.scilifelab.se/researcher/49b1e7e1fca74be090072ad2185c9827.json"}}, {"family": "Byzia", "given": "Anna", "initials": "A"}, {"family": "Ivanova", "given": "Aneta", "initials": "A"}, {"family": "Whelan", "given": "James", "initials": "J"}, {"family": "Drag", "given": "Marcin", "initials": "M"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Glaser", "given": "Elzbieta", "initials": "E"}], "type": "journal article", "published": "2017-01-00", "journal": {"volume": "13", "issn": "1552-4469", "issue": "1", "pages": "15-17", "title": "Nat. Chem. Biol.", "issn-l": "1552-4450"}, "abstract": "Plastids (including chloroplasts) are subcellular sites for a plethora of proteolytic reactions, required in functions ranging from protein biogenesis to quality control. Here we show that peptides generated from pre-protein maturation within chloroplasts of Arabidopsis thaliana are degraded to amino acids by a multi-step peptidolytic cascade consisting of oligopeptidases and aminopeptidases, effectively allowing the recovery of single amino acids within these organelles.", "doi": "10.1038/nchembio.2227", "pmid": "27820795", "labels": {"Clinical Proteomics Mass spectrometry": "Collaborative", "Global Proteomics and Proteogenomics": "Collaborative", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "nchembio.2227"}], "notes": [], "created": "2017-05-03T12:59:39.078Z", "modified": "2025-10-17T13:03:19.180Z"}, {"entity": "publication", "iuid": "f0189e06f40849b6aa396efe9d60aad1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0189e06f40849b6aa396efe9d60aad1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0189e06f40849b6aa396efe9d60aad1"}}, "title": "Validation and development of MTH1 inhibitors for treatment of cancer.", "authors": [{"family": "Warpman Berglund", "given": "U", "initials": "U"}, {"family": "Sanjiv", "given": "K", "initials": "K"}, {"family": "Gad", "given": "H", "initials": "H"}, {"family": "Kalder\u00e9n", "given": "C", "initials": "C"}, {"family": "Koolmeister", "given": "T", "initials": "T"}, {"family": "Pham", "given": "T", "initials": "T"}, {"family": "Gokturk", "given": "C", "initials": "C"}, {"family": "Jafari", "given": "R", "initials": "R"}, {"family": "Maddalo", "given": "G", "initials": "G"}, {"family": "Seashore-Ludlow", "given": "B", "initials": "B"}, {"family": "Chernobrovkin", "given": "A", "initials": "A"}, {"family": "Manoilov", "given": "A", "initials": "A"}, {"family": "Pateras", "given": "I S", "initials": "IS"}, {"family": "Rasti", "given": "A", "initials": "A"}, {"family": "Jemth", "given": "A-S", "initials": "AS"}, {"family": "Alml\u00f6f", "given": "I", "initials": "I"}, {"family": "Loseva", "given": "O", "initials": "O"}, {"family": "Visnes", "given": "T", "initials": "T"}, {"family": "Einarsdottir", "given": "B O", "initials": "BO"}, {"family": "Gaugaz", "given": "F Z", "initials": "FZ"}, {"family": "Saleh", "given": "A", "initials": "A"}, {"family": "Platzack", "given": "B", "initials": "B"}, {"family": "Wallner", "given": "O A", "initials": "OA"}, {"family": "Vallin", "given": "K S A", "initials": "KS"}, {"family": "Henriksson", "given": "M", "initials": "M"}, {"family": "Wakchaure", "given": "P", "initials": "P"}, {"family": "Borhade", "given": "S", "initials": "S"}, {"family": "Herr", "given": "P", "initials": "P"}, {"family": "Kallberg", "given": "Y", "initials": "Y"}, {"family": "Baranczewski", "given": "P", "initials": "P"}, {"family": "Homan", "given": "E J", "initials": "EJ"}, {"family": "Wiita", "given": "E", "initials": "E"}, {"family": "Nagpal", "given": "V", "initials": "V"}, {"family": "Meijer", "given": "T", "initials": "T"}, {"family": "Schipper", "given": "N", "initials": "N"}, {"family": "Rudd", "given": "S G", "initials": "SG"}, {"family": "Br\u00e4utigam", "given": "L", "initials": "L"}, {"family": "Lindqvist", "given": "A", "initials": "A"}, {"family": "Filppula", "given": "A", "initials": "A"}, {"family": "Lee", "given": "T-C", "initials": "TC"}, {"family": "Artursson", "given": "P", "initials": "P"}, {"family": "Nilsson", "given": "J A", "initials": "JA"}, {"family": "Gorgoulis", "given": "V G", "initials": "VG"}, {"family": "Lehti\u00f6", "given": "J", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Zubarev", "given": "R A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Scobie", "given": "M", "initials": "M"}, {"family": "Helleday", "given": "T", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2016-12-00", "journal": {"volume": "27", "issn": "1569-8041", "issue": "12", "pages": "2275-2283", "title": "Ann. Oncol.", "issn-l": "0923-7534"}, "abstract": "Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment.\n\nHuman cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models.\n\nHere, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo.\n\nWe demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.", "doi": "10.1093/annonc/mdw429", "pmid": "27827301", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Clinical Proteomics Mass spectrometry": "Collaborative", "Chemical Proteomics": "Service", "Advanced Mass Spectrometry Proteomics": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative", "Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0923-7534(19)36552-4"}], "notes": "Laboratories for Chemical Biology at Karolinska Institutet (LCBKI)\r\nADME of Therapeutics (UDOPP)", "created": "2017-05-03T12:58:49.192Z", "modified": "2025-10-17T13:05:09.110Z"}, {"entity": "publication", "iuid": "4f90bb3bf07a4fe28c6fd66458e7aa15", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4f90bb3bf07a4fe28c6fd66458e7aa15.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4f90bb3bf07a4fe28c6fd66458e7aa15"}}, "title": "Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves.", "authors": [{"family": "Maleki", "given": "Shohreh", "initials": "S"}, {"family": "Kjellqvist", "given": "Sanela", "initials": "S"}, {"family": "Paloschi", "given": "Valentina", "initials": "V"}, {"family": "Magn\u00e9", "given": "Joelle", "initials": "J"}, {"family": "Branca", "given": "Rui Miguel Mamede", "initials": "RM"}, {"family": "Du", "given": "Lei", "initials": "L"}, {"family": "Hultenby", "given": "Kjell", "initials": "K"}, {"family": "Petrini", "given": "Johan", "initials": "J"}, {"family": "Fuxe", "given": "Jonas", "initials": "J"}, {"family": "MIBAVA Leducq Consortium", "given": "", "initials": ""}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Franco-Cereceda", "given": "Anders", "initials": "A"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Bj\u00f6rck", "given": "Hanna M", "initials": "HM"}], "type": "journal article", "published": "2016-10-25", "journal": {"volume": "6", "issn": "2045-2322", "issue": null, "pages": "35712", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Individuals with a bicuspid aortic valve (BAV) are at significantly higher risk of developing aortic complications than individuals with tricuspid aortic valves (TAV) and defective signaling during the embryonic development and/or life time exposure to abnormal hemodynamic have been proposed as underlying factors. However, an explanation for the molecular mechanisms of aortopathy in BAV has not yet been provided. We combined proteomics, RNA analyses, immunohistochemistry, and electron microscopy to identify molecular differences in samples of non-dilated ascending aortas from BAV (N = 62) and TAV (N = 54) patients. Proteomic analysis was also performed for dilated aortas (N = 6 BAV and N = 5 TAV) to gain further insight into the aortopathy of BAV. Our results collectively showed the molecular signature of an endothelial/epithelial-mesenchymal (EndMT/EMT) transition-like process, associated with instability of intimal cell junctions and activation of RHOA pathway in the intima and media layers of ascending aorta in BAV patients. We propose that an improper regulation of EndMT/EMT during the spatiotemporally related embryogenesis of semilunar valves and ascending aorta in BAV individuals may result in aortic immaturity and instability prior to dilation. Exasperation of EndMT/EMT state in post embryonic life and/or exposure to non-physiological hemodynamic could lead to the aneurysm of ascending aorta in BAV individuals.", "doi": "10.1038/srep35712", "pmid": "27779199", "labels": {"Clinical Proteomics Mass spectrometry": "Collaborative", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "srep35712"}, {"db": "pmc", "key": "PMC5078843"}], "notes": [], "created": "2017-05-03T13:02:33.158Z", "modified": "2021-07-08T11:36:15.208Z"}, {"entity": "publication", "iuid": "2d1e0d8777f14467b95be4fa850cb8a6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2d1e0d8777f14467b95be4fa850cb8a6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2d1e0d8777f14467b95be4fa850cb8a6"}}, "title": "Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM.", "authors": [{"family": "Perisic Matic", "given": "Ljubica", "initials": "L"}, {"family": "Rykaczewska", "given": "Urszula", "initials": "U"}, {"family": "Razuvaev", "given": "Anton", "initials": "A"}, {"family": "Sabater-Lleal", "given": "Maria", "initials": "M"}, {"family": "Lengquist", "given": "Mariette", "initials": "M"}, {"family": "Miller", "given": "Clint L", "initials": "CL"}, {"family": "Ericsson", "given": "Ida", "initials": "I"}, {"family": "R\u00f6hl", "given": "Samuel", "initials": "S"}, {"family": "Kronqvist", "given": "Malin", "initials": "M"}, {"family": "Aldi", "given": "Silvia", "initials": "S"}, {"family": "Magn\u00e9", "given": "Joelle", "initials": "J"}, {"family": "Paloschi", "given": "Valentina", "initials": "V"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M"}, {"family": "Li", "given": "Yuhuang", "initials": "Y"}, {"family": "Jin", "given": "Hong", "initials": "H"}, {"family": "Diez", "given": "Maria Gonzalez", "initials": "MG"}, {"family": "Roy", "given": "Joy", "initials": "J"}, {"family": "Baldassarre", "given": "Damiano", "initials": "D"}, {"family": "Veglia", "given": "Fabrizio", "initials": "F"}, {"family": "Humphries", "given": "Steve E", "initials": "SE"}, {"family": "de Faire", "given": "Ulf", "initials": "U"}, {"family": "Tremoli", "given": "Elena", "initials": "E"}, {"family": "Odeberg", "given": "Jacob", "initials": "J"}, {"family": "Vukojevi\u0107", "given": "Vladana", "initials": "V"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Maegdefessel", "given": "Lars", "initials": "L"}, {"family": "Ehrenborg", "given": "Ewa", "initials": "E"}, {"family": "Paulsson-Berne", "given": "Gabrielle", "initials": "G"}, {"family": "Hansson", "given": "G\u00f6ran K", "initials": "GK"}, {"family": "Lindeman", "given": "Jan H N", "initials": "JH"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Quertermous", "given": "Thomas", "initials": "T"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Hedin", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2016-09-00", "journal": {"volume": "36", "issn": "1524-4636", "issue": "9", "pages": "1947-1961", "title": "Arterioscler. Thromb. Vasc. Biol.", "issn-l": "1079-5642"}, "abstract": "Key augmented processes in atherosclerosis have been identified, whereas less is known about downregulated pathways. Here, we applied a systems biology approach to examine suppressed molecular signatures, with the hypothesis that they may provide insight into mechanisms contributing to plaque stability.\n\nMuscle contraction, muscle development, and actin cytoskeleton were the most downregulated pathways (false discovery rate=6.99e-21, 1.66e-6, 2.54e-10, respectively) in microarrays from human carotid plaques (n=177) versus healthy arteries (n=15). In addition to typical smooth muscle cell (SMC) markers, these pathways also encompassed cytoskeleton-related genes previously not associated with atherosclerosis. SYNPO2, SYNM, LMOD1, PDLIM7, and PLN expression positively correlated to typical SMC markers in plaques (Pearson r>0.6, P<0.0001) and in rat intimal hyperplasia (r>0.8, P<0.0001). By immunohistochemistry, the proteins were expressed in SMCs in normal vessels, but largely absent in human plaques and intimal hyperplasia. Subcellularly, most proteins localized to the cytoskeleton in cultured SMCs and were regulated by active enhancer histone modification H3K27ac by chromatin immunoprecipitation-sequencing. Functionally, the genes were downregulated by PDGFB (platelet-derived growth factor beta) and IFNg (interferron gamma), exposure to shear flow stress, and oxLDL (oxidized low-density lipoprotein) loading. Genetic variants in PDLIM7, PLN, and SYNPO2 loci associated with progression of carotid intima-media thickness in high-risk subjects without symptoms of cardiovascular disease (n=3378). By eQTL (expression quantitative trait locus), rs11746443 also associated with PDLIM7 expression in plaques. Mechanistically, silencing of PDLIM7 in vitro led to downregulation of SMC markers and disruption of the actin cytoskeleton, decreased cell spreading, and increased proliferation.\n\nWe identified a panel of genes that reflect the altered phenotype of SMCs in vascular disease and could be early sensitive markers of SMC dedifferentiation.", "doi": "10.1161/ATVBAHA.116.307893", "pmid": "27470516", "labels": {"Clinical Proteomics Mass spectrometry": "Collaborative", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "ATVBAHA.116.307893"}], "notes": [], "created": "2017-05-03T13:02:33.883Z", "modified": "2021-07-08T11:36:15.145Z"}, {"entity": "publication", "iuid": "7d3a9a83444049e8b4d26652d57f1ad6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7d3a9a83444049e8b4d26652d57f1ad6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7d3a9a83444049e8b4d26652d57f1ad6"}}, "title": "Single base resolution analysis of 5-hydroxymethylcytosine in 188 human genes: implications for hepatic gene expression.", "authors": [{"family": "Ivanov", "given": "Maxim", "initials": "M"}, {"family": "Kals", "given": "Mart", "initials": "M"}, {"family": "Lauschke", "given": "Volker", "initials": "V"}, {"family": "Barragan", "given": "Isabel", "initials": "I"}, {"family": "Ewels", "given": "Philip", "initials": "P"}, {"family": "K\u00e4ller", "given": "Max", "initials": "M", "orcid": "0000-0001-6813-3051", "researcher": {"href": "https://publications.scilifelab.se/researcher/536ad902a272482aba853c078557e240.json"}}, {"family": "Axelsson", "given": "Tomas", "initials": "T"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Milani", "given": "Lili", "initials": "L"}, {"family": "Ingelman-Sundberg", "given": "Magnus", "initials": "M"}], "type": "journal article", "published": "2016-08-19", "journal": {"volume": "44", "issn": "1362-4962", "issue": "14", "pages": "6756-6769", "title": "Nucleic Acids Res.", "issn-l": "0305-1048"}, "abstract": "To improve the epigenomic analysis of tissues rich in 5-hydroxymethylcytosine (hmC), we developed a novel protocol called TAB-Methyl-SEQ, which allows for single base resolution profiling of both hmC and 5-methylcytosine by targeted next-generation sequencing. TAB-Methyl-SEQ data were extensively validated by a set of five methodologically different protocols. Importantly, these extensive cross-comparisons revealed that protocols based on Tet1-assisted bisulfite conversion provided more precise hmC values than TrueMethyl-based methods. A total of 109 454 CpG sites were analyzed by TAB-Methyl-SEQ for mC and hmC in 188 genes from 20 different adult human livers. We describe three types of variability of hepatic hmC profiles: (i) sample-specific variability at 40.8% of CpG sites analyzed, where the local hmC values correlate to the global hmC content of livers (measured by LC-MS), (ii) gene-specific variability, where hmC levels in the coding regions positively correlate to expression of the respective gene and (iii) site-specific variability, where prominent hmC peaks span only 1 to 3 neighboring CpG sites. Our data suggest that both the gene- and site-specific components of hmC variability might contribute to the epigenetic control of hepatic genes. The protocol described here should be useful for targeted DNA analysis in a variety of applications.", "doi": "10.1093/nar/gkw316", "pmid": "27131363", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Clinical Proteomics Mass spectrometry": "Collaborative", "NGI Stockholm (Genomics Applications)": "Collaborative", "NGI Stockholm (Genomics Production)": "Collaborative", "National Genomics Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "gkw316"}, {"db": "pmc", "key": "PMC5001587"}], "notes": [], "created": "2017-05-03T13:00:08.926Z", "modified": "2024-01-16T13:48:49.630Z"}, {"entity": "publication", "iuid": "cfe4260e16314a9ea8a28ff73a6111df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cfe4260e16314a9ea8a28ff73a6111df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cfe4260e16314a9ea8a28ff73a6111df"}}, "title": "Cells release subpopulations of exosomes with distinct molecular and biological properties.", "authors": [{"family": "Willms", "given": "Eduard", "initials": "E"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "M\u00e4ger", "given": "Imre", "initials": "I"}, {"family": "Lee", "given": "Yi", "initials": "Y"}, {"family": "Blomberg", "given": "K Emelie M", "initials": "KE"}, {"family": "Sadik", "given": "Mariam", "initials": "M"}, {"family": "Alaarg", "given": "Amr", "initials": "A"}, {"family": "Smith", "given": "C I Edvard", "initials": "CI"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "El Andaloussi", "given": "Samir", "initials": "S"}, {"family": "Wood", "given": "Matthew J A", "initials": "MJ"}, {"family": "Vader", "given": "Pieter", "initials": "P"}], "type": "journal article", "published": "2016-03-02", "journal": {"volume": "6", "issn": "2045-2322", "issue": null, "pages": "22519", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Cells release nano-sized membrane vesicles that are involved in intercellular communication by transferring biological information between cells. It is generally accepted that cells release at least three types of extracellular vesicles (EVs): apoptotic bodies, microvesicles and exosomes. While a wide range of putative biological functions have been attributed to exosomes, they are assumed to represent a homogenous population of EVs. We hypothesized the existence of subpopulations of exosomes with defined molecular compositions and biological properties. Density gradient centrifugation of isolated exosomes revealed the presence of two distinct subpopulations, differing in biophysical properties and their proteomic and RNA repertoires. Interestingly, the subpopulations mediated differential effects on the gene expression programmes in recipient cells. In conclusion, we demonstrate that cells release distinct exosome subpopulations with unique compositions that elicit differential effects on recipient cells. Further dissection of exosome heterogeneity will advance our understanding of exosomal biology in health and disease and accelerate the development of exosome-based diagnostics and therapeutics.", "doi": "10.1038/srep22519", "pmid": "26931825", "labels": {"Clinical Proteomics Mass spectrometry": "Technology development"}, "xrefs": [{"db": "pii", "key": "srep22519"}, {"db": "pmc", "key": "PMC4773763"}], "notes": [], "created": "2017-05-03T13:02:32.859Z", "modified": "2021-07-08T11:36:15.276Z"}, {"entity": "publication", "iuid": "150901597106460ca19322b5e9e8a83d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/150901597106460ca19322b5e9e8a83d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/150901597106460ca19322b5e9e8a83d"}}, "title": "Comprehensive Proteomic Analysis of Mesenchymal Stem Cell Exosomes Reveals Modulation of Angiogenesis via Nuclear Factor-KappaB Signaling.", "authors": [{"family": "Anderson", "given": "Johnathon D", "initials": "JD"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Graham", "given": "Calvin S", "initials": "CS"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M"}, {"family": "Pham", "given": "Missy T", "initials": "MT"}, {"family": "Bramlett", "given": "Charles S", "initials": "CS"}, {"family": "Montgomery", "given": "Elizabeth N", "initials": "EN"}, {"family": "Mellema", "given": "Matt S", "initials": "MS"}, {"family": "Bardini", "given": "Renee L", "initials": "RL"}, {"family": "Contreras", "given": "Zelenia", "initials": "Z"}, {"family": "Hoon", "given": "Madeline", "initials": "M"}, {"family": "Bauer", "given": "Gerhard", "initials": "G"}, {"family": "Fink", "given": "Kyle D", "initials": "KD"}, {"family": "Fury", "given": "Brian", "initials": "B"}, {"family": "Hendrix", "given": "Kyle J", "initials": "KJ"}, {"family": "Chedin", "given": "Frederic", "initials": "F"}, {"family": "El-Andaloussi", "given": "Samir", "initials": "S"}, {"family": "Hwang", "given": "Billie", "initials": "B"}, {"family": "Mulligan", "given": "Michael S", "initials": "MS"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Nolta", "given": "Jan A", "initials": "JA"}], "type": "journal article", "published": "2016-03-00", "journal": {"volume": "34", "issn": "1549-4918", "issue": "3", "pages": "601-613", "title": "Stem Cells", "issn-l": "1066-5099"}, "abstract": "Mesenchymal stem cells (MSC) are known to facilitate healing of ischemic tissue related diseases through proangiogenic secretory proteins. Recent studies further show that MSC derived exosomes function as paracrine effectors of angiogenesis, however, the identity of which components of the exosome proteome responsible for this effect remains elusive. To address this we used high-resolution isoelectric focusing coupled liquid chromatography tandem mass spectrometry, an unbiased high throughput proteomics approach to comprehensively characterize the proteinaceous contents of MSCs and MSC derived exosomes. We probed the proteome of MSCs and MSC derived exosomes from cells cultured under expansion conditions and under ischemic tissue simulated conditions to elucidate key angiogenic paracrine effectors present and potentially differentially expressed in these conditions. In total, 6,342 proteins were identified in MSCs and 1,927 proteins in MSC derived exosomes, representing to our knowledge the first time these proteomes have been probed comprehensively. Multilayered analyses identified several putative paracrine effectors of angiogenesis present in MSC exosomes and increased in expression in MSCs exposed to ischemic tissue-simulated conditions; these include platelet derived growth factor, epidermal growth factor, fibroblast growth factor, and most notably nuclear factor-kappaB (NFkB) signaling pathway proteins. NFkB signaling was identified as a key mediator of MSC exosome induced angiogenesis in endothelial cells by functional in vitro validation using a specific inhibitor. Collectively, the results of our proteomic analysis show that MSC derived exosomes contain a robust profile of angiogenic paracrine effectors, which have potential for the treatment of ischemic tissue-related diseases.", "doi": "10.1002/stem.2298", "pmid": "26782178", "labels": {"Clinical Proteomics Mass spectrometry": "Collaborative", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC5785927"}, {"db": "mid", "key": "NIHMS932042"}], "notes": [], "created": "2017-05-03T13:02:32.246Z", "modified": "2021-07-08T11:36:15.138Z"}, {"entity": "publication", "iuid": "c2a7d6add2784a56baf3f80c90b065eb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c2a7d6add2784a56baf3f80c90b065eb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c2a7d6add2784a56baf3f80c90b065eb"}}, "title": "Multi-omic data analysis using Galaxy.", "authors": [{"family": "Boekel", "given": "Jorrit", "initials": "J"}, {"family": "Chilton", "given": "John M", "initials": "JM"}, {"family": "Cooke", "given": "Ira R", "initials": "IR"}, {"family": "Horvatovich", "given": "Peter L", "initials": "PL"}, {"family": "Jagtap", "given": "Pratik D", "initials": "PD"}, {"family": "K\u00e4ll", "given": "Lukas", "initials": "L"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Lukasse", "given": "Pieter", "initials": "P"}, {"family": "Moerland", "given": "Perry D", "initials": "PD"}, {"family": "Griffin", "given": "Timothy J", "initials": "TJ"}], "type": "journal article", "published": "2015-02-00", "journal": {"volume": "33", "issn": "1546-1696", "issue": "2", "pages": "137-139", "title": "Nat. Biotechnol.", "issn-l": "1087-0156"}, "abstract": null, "doi": "10.1038/nbt.3134", "pmid": "25658277", "labels": {"Clinical Proteomics Mass spectrometry": null, "Bioinformatics Support, Infrastructure and Training": null, "Bioinformatics Support and Infrastructure": null, "Bioinformatics (NBIS)": null}, "xrefs": [{"db": "pii", "key": "nbt.3134"}], "notes": [], "created": "2017-05-02T12:56:37.598Z", "modified": "2021-07-08T11:36:15.267Z"}, {"entity": "publication", "iuid": "49dc029151504b1cb7be57b1ebc26237", "links": {"self": {"href": "https://publications.scilifelab.se/publication/49dc029151504b1cb7be57b1ebc26237.json"}, "display": {"href": "https://publications.scilifelab.se/publication/49dc029151504b1cb7be57b1ebc26237"}}, "title": "Abstract of the 35th Scandinavian Congress of Rheumatology, September 20-23, 2014, Stockholm, Sweden.", "authors": [], "type": "congress", "published": "2014-09-04", "journal": {"volume": "43", "issn": "1502-7740", "issue": "127", "pages": "1-97", "title": "Scand J Rheumatol Suppl", "issn-l": null}, "abstract": null, "doi": "10.3109/03009742.2014.946235", "pmid": "25184497", "labels": {"Clinical Proteomics Mass spectrometry": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:03:24.712Z", "modified": "2021-06-22T12:00:46.703Z"}, {"entity": "publication", "iuid": "0fe1e59a92db484ead8642f49cef0d4b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0fe1e59a92db484ead8642f49cef0d4b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0fe1e59a92db484ead8642f49cef0d4b"}}, "title": "Stable isotope labeling methods in protein profiling.", "authors": [{"family": "Lengqvist", "given": "Johan", "initials": "J"}, {"family": "Sandberg", "given": "AnnSofi", "initials": "A"}], "type": "journal article", "published": "2013-06-15", "journal": {"volume": "1023", "issn": "1940-6029", "issue": null, "pages": "21-51", "title": "Methods Mol. Biol.", "issn-l": "1064-3745"}, "abstract": "Mass spectrometry (MS) analysis of peptides and proteins has evolved dramatically over the last 20 years. Improvement of MS instrumentation, computational data analysis, and the availability of complete sequence databases for many species have made large-scale proteomics analyses possible. The measurement of global protein abundance by quantitative mass spectrometry has the potential to increase both speed and impact of biological and clinical research. However, to be able to detect and identify potential biomarkers, reproducible and accurate quantification is essential. The following chapter describes how to perform quantitative protein profiling using stable isotope labeling methods. Throughout, there is a focus on guidance in selection of an appropriate labeling strategy. With that in mind, we have included a section on acquisition and understanding of the liquid chromatography-mass spectrometry (LC-MS) data format. Further, we describe the different stable isotope labeling methods and their pros and cons. We start by giving an overview of the overall quantitative proteomics workflow in which extracting relevant biological information from the acquired data is the ultimate goal.", "doi": "10.1007/978-1-4614-7209-4_3", "pmid": "23765618", "labels": {"Clinical Proteomics Mass spectrometry": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:03:23.801Z", "modified": "2023-06-19T12:55:00.440Z"}, {"entity": "publication", "iuid": "2e42e8d0491849e18636a9542a65ef10", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2e42e8d0491849e18636a9542a65ef10.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2e42e8d0491849e18636a9542a65ef10"}}, "title": "Protein quantification by peptide quality control (PQPQ) of shotgun proteomics data.", "authors": [{"family": "Forshed", "given": "Jenny", "initials": "J"}], "type": "journal article", "published": "2013-06-15", "journal": {"volume": "1023", "issn": "1940-6029", "issue": null, "pages": "149-158", "title": "Methods Mol. Biol.", "issn-l": "1064-3745"}, "abstract": "This chapter describes how to improve quantitative accuracy and precision in shotgun proteomics by PQPQ (protein quantification by peptide quality control). The method is based on the assumption that the quantitative pattern of peptides derived from one protein will correlate over several samples. Dissonant patterns are assumed to arise either from mismatched peptides or due to the presence of different protein species. PQPQ identifies and excludes outliers and detects the existence of different protein species by correlation analysis. Alternative protein species can then be quantified separately. PQPQ can handle shotgun proteomics data from several MS instruments, data from different kinds of labeling, and label-free data. We have previously shown that data processing by PQPQ improves the information output from shotgun proteomics by validating the algorithm on seven datasets related to different cancer studies (Forshed et al., Mol Cell Proteomics 10(10):M111.010264, 2011). Data from two labeling procedures and three different instrumental platforms was included in the evaluation. With this unique method using both peptide sequence data and quantitative data, we can improve the quantitative accuracy and precision on the protein level and detect different protein species (Forshed et al., Mol Cell Proteomics 10(10):M111.010264, 2011).", "doi": "10.1007/978-1-4614-7209-4_9", "pmid": "23765624", "labels": {"Clinical Proteomics Mass spectrometry": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:03:23.206Z", "modified": "2017-05-30T12:42:45.953Z"}, {"entity": "publication", "iuid": "2e1fe44fabcf483abdd700396ed83d4e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2e1fe44fabcf483abdd700396ed83d4e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2e1fe44fabcf483abdd700396ed83d4e"}}, "title": "Narrow-range peptide isoelectric focusing as peptide prefractionation method prior to tandem mass spectrometry analysis.", "authors": [{"family": "Pernemalm", "given": "Maria", "initials": "M", "orcid": "0000-0003-4624-031X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f15f303cb2044cfa81719700137e3603.json"}}], "type": "journal article", "published": "2013-06-15", "journal": {"volume": "1023", "issn": "1940-6029", "issue": null, "pages": "3-11", "title": "Methods Mol. Biol.", "issn-l": "1064-3745"}, "abstract": "High sample complexity is one of the major challenges in mass spectrometry-based proteomics today. Despite massive improvement in instrumentation, sample prefractionation is still needed to reduce sample complexity and improve proteome coverage. Isoelectric focusing (IEF) has been traditionally used as a first-dimension protein separation technique in two-dimensional gel electrophoresis-based proteomics. Recently, peptide IEF has emerged as appealing alternative for anion exchange chromatography in multidimensional LC-MS/MS workflows. The rationale behind using narrow-range peptide isoelectric focusing as a prefractionation method prior to ms/ms is to reduce the complexity induced by tryptic digestion. This is done by selectively analyzing a sub-fraction of peptides with an acidic pI. The pI range is chosen as it has previously been shown that 96 % of human proteins have at least one tryptic peptide between pH 3.4 and 4.9. This ensures high proteome coverage while reducing the number of peptides with 2/3. In addition the focusing precision is optimal in this range. Therefore, by analyzing this sub-fraction of peptides the complexity of the sample can be reduced without significant loss of proteome coverage. As the theoretical pI of peptides can be calculated, the pI of the identified peptides can be used to validate the peptide sequence (identified peptides with pI outside the pH range 3.4-4.9 are more likely to be false positives). In addition, this approach is compatible with iTRAQ labelling as the different iTRAQ labels migrate similarly in IEF.", "doi": "10.1007/978-1-4614-7209-4_1", "pmid": "23765616", "labels": {"Clinical Proteomics Mass spectrometry": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:03:24.100Z", "modified": "2021-07-08T11:36:54.632Z"}, {"entity": "publication", "iuid": "afd562f281744bc99a19b35dbd0c972d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/afd562f281744bc99a19b35dbd0c972d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/afd562f281744bc99a19b35dbd0c972d"}}, "title": "Comprehensive analysis of MHC ligands in clinical material by immunoaffinity-mass spectrometry.", "authors": [{"family": "Kasuga", "given": "Kie", "initials": "K"}], "type": "journal article", "published": "2013-06-15", "journal": {"volume": "1023", "issn": "1940-6029", "issue": null, "pages": "203-218", "title": "Methods Mol. Biol.", "issn-l": "1064-3745"}, "abstract": "Major histocompatibility complexes (MHC) are expressed on antigen-presenting cells (APC) that display peptide antigens. This is a crucial step to activate a T-cell response. Since immunogenic ligand of MHC is closely related with autoimmunity, inflammatory diseases, and cancer, comprehensive analysis of MHC ligands (the so-called Ligandome) is essential to unveil disease pathogenesis. Recently, immunotherapies such as vaccination have been focused on as new therapies of cancer, HIV, and infectious diseases. Therefore, the importance of comprehensive analysis of MHC ligands is increasing. Mass spectrometry has been the core technology of ligand identification since the 1990s. The sensitivity of mass spectrometers has been improved dramatically in recent years; thus, it enables to identify MHC ligands in clinical materials. This chapter lays out the workflow of MHC ligand identification in clinical materials, especially human bronchoalveolar (BAL) cells. MHC-ligand complexes are enriched by immunoaffinity extraction and captured ligand peptides are identified by LC-MS/MS. MHC class II ligand in BAL cells is described in this text; however, this approach is applicable to MHC class I and other clinical materials such as tissues.", "doi": "10.1007/978-1-4614-7209-4_14", "pmid": "23765629", "labels": {"Clinical Proteomics Mass spectrometry": null}, "xrefs": [], "notes": [], "created": "2017-05-04T15:03:23.503Z", "modified": "2017-05-30T12:42:50.697Z"}]}