| 1. |
- Bergquist, Jonas, et al.
(författare)
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Peptide Mapping of Proteins in Human Body Fluids using Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry
- 2002
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Ingår i: Mass spectrometry reviews (Print). - : Wiley. - 0277-7037 .- 1098-2787. ; 21:1, s. 2-15
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Tidskriftsartikel (refereegranskat)abstract
- Human body fluids have been rediscovered in the postgenomic era as great sources of biological markers and perhaps particularly as sources of potential protein biomarkers of disease. Analytical tools that allow rapid screening, low sample consumption, and accurate protein identification are of great importance in studies of complex biological samples and clinical diagnosis. Mass spectrometry is today one of the most important analytical tools with applications in a wide variety of fields. One of the fastest growing applications is in proteomics, or the study of protein expression in an organism. Mass spectrometry has been used to find post-translational modifications and to identify key functions of proteins in the human body. In this study, we review the use of human body fluids as sources for clinical markers and present new data that show the ability of Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) to identify, and characterize proteins in four human body fluids: plasma, cerebrospinal fluid (CSF), saliva, and urine. The body fluids were tryptically digested without any prior separation, purification, or selection, and the digest was introduced into a 9.4 T FTICR mass spectrometer by direct-infusion electrospray ionization (ESI). Even though these samples represent complex biological mixtures, the described method provides information that is comparable with traditional 2D-PAGE data. The sample consumption is extremely low, a few microliters, and the analysis time is only a few minutes. It is, however evident that the separation of proteins and/or peptides must be included in the methodology in order to detect low-abundance proteins and other proteins of biological relevance.
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| 2. |
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| 3. |
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| 4. |
- Palmblad, Magnus, et al.
(författare)
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Analysis of Enzymatically Digested Proteins and Protein Mixtures using a 9.4 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometer
- 2000
-
Ingår i: Rapid Communications in Mass Spectrometry. - 0951-4198 .- 1097-0231. ; 14:12, s. 1029-1034
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Tidskriftsartikel (refereegranskat)abstract
- A commercially available 9.4 Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer was applied in the analysis of tryptic digests of protein mixtures without any separation. First, the method was demonstrated on a mixture of tryptic digests of equine cytochrome c, equine myoglobin and bovine serum albumin. The same method was then applied to human plasma from a healthy blood donor. Computer programs were employed to simplify analysis of the complex spectra. The 2745 peaks in the human plasma electrospray ionization FTICR spectrum could be reduced to 1165 isotopic clusters and 669 unique masses. Out of these, 82 masses matched tryptic fragments of serum albumin with mass measurement errors less than 10 ppm, covering 93% of the sequence. Another 16 masses were assigned to tryptic fragments of transferrin, covering 41% of the sequence on the 10 ppm mass measurement error level (14 within 2 ppm). The mass measurement errors were approximately normal distributed with a standard deviation of 1.7 ppm. This demonstrates the feasibility of combining the ultra-high mass resolving power and accuracy of FTICR mass spectrometry with automated computer analysis for investigating complex biological matrices.
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| 5. |
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| 6. |
- Adhikari, Subash, et al.
(författare)
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A high-stringency blueprint of the human proteome
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Forskningsöversikt (refereegranskat)abstract
- The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
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| 7. |
- Axelsson, Jan, et al.
(författare)
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Electron Capture Dissociation of Substance-P using a Commercially Available Fourier Transform Ion Cyclotron Resonance Mass Spectrometer
- 1999
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Ingår i: Rapid Communications in Mass Spectrometry. - 0951-4198 .- 1097-0231. ; 13:6, s. 474-477
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Tidskriftsartikel (refereegranskat)abstract
- Electron capture dissociation of the peptide Substance P is reported for the first time, with an unmodified, commercially available Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. The fragmentation pattern is compared with that obtained with collisionally induced dissociation of the ions in the electrospray ion source, and note that electron capture dissociation gives a more easily interpreted spectrum, showing mainly C-fragments. With the exception of the proline residues, which require cleavage of two chemical bonds, we observe all C-fragmental we find the bias voltage of the electron gun not to be very critical.
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| 8. |
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| 9. |
- Bouyssié, David, et al.
(författare)
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WOMBAT-P : Benchmarking Label-Free Proteomics Data Analysis Workflows
- 2024
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Ingår i: Journal of Proteome Research. - 1535-3893. ; 23:1, s. 418-429
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Tidskriftsartikel (refereegranskat)abstract
- The inherent diversity of approaches in proteomics research has led to a wide range of software solutions for data analysis. These software solutions encompass multiple tools, each employing different algorithms for various tasks such as peptide-spectrum matching, protein inference, quantification, statistical analysis, and visualization. To enable an unbiased comparison of commonly used bottom-up label-free proteomics workflows, we introduce WOMBAT-P, a versatile platform designed for automated benchmarking and comparison. WOMBAT-P simplifies the processing of public data by utilizing the sample and data relationship format for proteomics (SDRF-Proteomics) as input. This feature streamlines the analysis of annotated local or public ProteomeXchange data sets, promoting efficient comparisons among diverse outputs. Through an evaluation using experimental ground truth data and a realistic biological data set, we uncover significant disparities and a limited overlap in the quantified proteins. WOMBAT-P not only enables rapid execution and seamless comparison of workflows but also provides valuable insights into the capabilities of different software solutions. These benchmarking metrics are a valuable resource for researchers in selecting the most suitable workflow for their specific data sets. The modular architecture of WOMBAT-P promotes extensibility and customization. The software is available at https://github.com/wombat-p/WOMBAT-Pipelines.
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| 10. |
- Carlsson, Göran, 1951, et al.
(författare)
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Incidence of severe congenital neutropenia in Sweden and risk of evolution to myelodysplastic syndrome/leukaemia.
- 2012
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Ingår i: British journal of haematology. - : Wiley. - 1365-2141 .- 0007-1048. ; 158:3, s. 363-369
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Tidskriftsartikel (refereegranskat)abstract
- Severe congenital neutropenia (SCN) is characterized by low blood neutrophil counts, early bacterial infections, and risk of leukaemia development. As yet, no population-based incidence estimates of SCN have been reported. Children less than 16years of age with SCN were sought in Sweden during the 20-year period 1987-2006 by a questionnaire to all Swedish Departments of Paediatrics and by reviewing the Swedish Health and Welfare Statistical Databases. Thirty-two patients were diagnosed with congenital neutropenia during this period. All received treatment with recombinant granulocyte-colony stimulating factor (G-CSF). Twenty-one patients were diagnosed as SCN or probable SCN, corresponding to 1·0 per 100000 live births. Nine (43%) had ELANE mutations, four (19%) HAX1 mutations and eight (38%) were children with disease of unknown genetic aetiology. Four out of 21 patients (19%) developed myelodysplastic syndrome/leukaemia and three (14%) died, all with leukaemia. The cumulative incidence of myelodysplastic syndrome/leukaemia was 31%. The observed incidence of SCN in this population-based study was higher than previously estimated, possibly because genetic testing now can identify SCN cases previously thought to be idiopathic or benign neutropenia. The risk of developing myelodysplastic syndrome/leukaemia is considerable. ELANE mutations are the most commonly identified genetic defects.
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| 11. |
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| 12. |
- Carlsson, Göran, et al.
(författare)
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Kostmann syndrome or infantile genetic agranulocytosis, part two : Understanding the underlying genetic defects in severe congenital neutropenia
- 2007
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 96:6, s. 813-819
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Forskningsöversikt (refereegranskat)abstract
- Congenital neutropenia in man was first reported 50 years ago by the Swedish paediatrician Rolf Kostmann. He coined the term 'infantile genetic agranulocytosis' for this condition, which is now known as Kostmann syndrome. Recent studies have revealed mutations in ELA-2, encoding the neutrophil granule protease, neutrophil elastase, in autosomal dominant neutropenia, and mutations in HAX-1, encoding an anti-apoptotic protein, in autosomal recessive neutropenia. Conclusion: Future studies should aim to clarify the mechanisms underlying the evolution of secondary malignancies in these patients.
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| 13. |
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| 14. |
- Ejerblad, Elisabeth, et al.
(författare)
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Diagnosis according to World Health Organization determines the long-term prognosis in patients with myeloproliferative neoplasms treated with anagrelide : Results of a prospective long-term follow-up
- 2013
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Ingår i: Hematology. - 1024-5332 .- 1607-8454. ; 18:1, s. 8-13
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:During long term follow-up of a cohort of patients with essential thrombocythemia (ET) and polycythemia vera (PV) a higher than expected incidence of myelofibrosis (MF) was noted. In order to test if the explanation could be found in the diagnostic criteria a re-evaluation of diagnosis using the 2008 WHO diagnostic criteria for ET and MF was performed.METHODS: This prospective study of 60 patients with ET and PV was set up in 1998 to evaluate the long-term efficacy and tolerability of anagrelide treatment. Bone marrow trephine biopsies were requested from study start, after 2 and 7 years of follow-up. A blinded re-evaluation of the bone marrow trephines was performed. The 2008 WHO bone marrow criteria were used for diagnosis and fibrosis grading.RESULTS: Of 40 patients with an initial diagnosis of ET, 21 were confirmed as 'true ET' whereas 17 were reclassified as primary myelofibrosis (PMF) (12 PMF-0, 3 PMF-1, 2 PMF-2) and 2 as myeloproliferative neoplasms of uncertain origin. After 7 years of follow-up, 19 of 21 patients with 'true ET' were alive, none had transformed to MF, leukemia, or myelodysplastic syndrome. In contrast, 4/17 patients reclassified as PMF had died, two patients transformed to myelodysplastic syndrome and 7 patients progressed to overt MF.DISCUSSION:We conclude that a blinded re-evaluation of bone marrow trephines from study start and after 7 years of follow-up using 2008 World Health Organization criteria was able to differentiate between true ET and PMF with a marked difference in follow-up outcome.
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| 15. |
- Jagtap, Pratik D., et al.
(författare)
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The Association of Biomolecular Resource Facilities Proteome Informatics Research Group Study on Metaproteomics (iPRG-2020)
- 2023
-
Ingår i: Journal of biomolecular techniques : JBT. - : Association of Biomolecular Resource Facilities. - 1943-4731. ; 34:3
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Tidskriftsartikel (refereegranskat)abstract
- Metaproteomics research using mass spectrometry data has emerged as a powerful strategy to understand the mechanisms underlying microbiome dynamics and the interaction of microbiomes with their immediate environment. Recent advances in sample preparation, data acquisition, and bioinformatics workflows have greatly contributed to progress in this field. In 2020, the Association of Biomolecular Research Facilities Proteome Informatics Research Group launched a collaborative study to assess the bioinformatics options available for metaproteomics research. The study was conducted in 2 phases. In the first phase, participants were provided with mass spectrometry data files and were asked to identify the taxonomic composition and relative taxa abundances in the samples without supplying any protein sequence databases. The most challenging question asked of the participants was to postulate the nature of any biological phenomena that may have taken place in the samples, such as interactions among taxonomic species. In the second phase, participants were provided a protein sequence database composed of the species present in the sample and were asked to answer the same set of questions as for phase 1. In this report, we summarize the data processing methods and tools used by participants, including database searching and software tools used for taxonomic and functional analysis. This study provides insights into the status of metaproteomics bioinformatics in participating laboratories and core facilities.
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| 16. |
- Johansson, Åsa, et al.
(författare)
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Identification of genetic variants influencing the human plasma proteome
- 2013
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:12, s. 4673-4678
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants influencing the transcriptome have been extensively studied. However, the impact of the genetic factors on the human proteome is largely unexplored, mainly due to lack of suitable high-throughput methods. Here we present unique and comprehensive identification of genetic variants affecting the human plasma protein profile by combining high-throughput and high-resolution mass spectrometry (MS) with genome-wide SNP data. We identified and quantified the abundance of 1,056 tryptic-digested peptides, representing 163 proteins in the plasma of 1,060 individuals from two population-based cohorts. The abundance level of almost one-fifth (19%) of the peptides was found to be heritable, with heritability ranging from 0.08 to 0.43. The levels of 60 peptides from 25 proteins, 15% of the proteins studied, were influenced by cis-acting SNPs. We identified and replicated individual cis-acting SNPs (combined P value ranging from 3.1 x 10(-52) to 2.9 x 10(-12)) influencing 11 peptides from 5 individual proteins. These SNPs represent both regulatory SNPs and nonsynonymous changes defining well-studied disease alleles such as the epsilon 4 allele of apolipoprotein E (APOE), which has been shown to increase risk of Alzheimer's disease. Our results show that high-throughput mass spectrometry represents a promising method for large-scale characterization of the human proteome, allowing for both quantification and sequencing of individual proteins. Abundance and peptide composition of a protein plays an important role in the etiology, diagnosis, and treatment of a number of diseases. A better understanding of the genetic impact on the plasma proteome is therefore important for evaluating potential biomarkers and therapeutic agents for common diseases.
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| 17. |
- Neely, Benjamin A., et al.
(författare)
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Toward an Integrated Machine Learning Model of a Proteomics Experiment
- 2023
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 22:3, s. 681-696
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Forskningsöversikt (refereegranskat)abstract
- In recent years machine learning has made extensive progress in modeling many aspects of mass spectrometry data. We brought together proteomics data generators, repository managers, and machine learning experts in a workshop with the goals to evaluate and explore machine learning applications for realistic modeling of data from multidimensional mass spectrometry-based proteomics analysis of any sample or organism. Following this sample-to-data roadmap helped identify knowledge gaps and define needs. Being able to generate bespoke and realistic synthetic data has legitimate and important uses in system suitability, method development, and algorithm benchmarking, while also posing critical ethical questions. The interdisciplinary nature of the workshop informed discussions of what is currently possible and future opportunities and challenges. In the following perspective we summarize these discussions in the hope of conveying our excitement about the potential of machine learning in proteomics and to inspire future research.
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| 18. |
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| 19. |
- Nilsson, Stefan, et al.
(författare)
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Explorative Study of the Protein Composition of Amniotic Fluid by Liquid Chromatography Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry
- 2004
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). ; 3:4, s. 884-889
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Tidskriftsartikel (refereegranskat)abstract
- To explore the suitability of FTICR mass spectrometry for the analysis of the protein composition of amniotic fluid (AF), an AF sample from 15 weeks gestation from a healthy 36-year-old woman was tryptically digested, with or without prior serum albumin removal. The tryptic peptides were separated by gradient capillary liquid chromatography (LC) followed by electrospray ionization (ESI) and mass spectrometric detection with a 9.4 T Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR). The obtained data underwent computer-aided mathematical and statistical evaluation to extract significant tryptic peptide patterns from human proteins. Forty-three proteins were putatively identified; among them were known protein constituents of amniotic fluid, but also many that not have been detected before. The removal of serum albumin prior to tryptic digestion reduced ion suppression from abundant HSA fragments. The protein analysis of amniotic fluid by albumin removal, tryptic digestion and LC/FT-ICR-MS analysis was found to be a straightforward technique.
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| 20. |
- Näsström, Mats, et al.
(författare)
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Projekt: Fastelaboratoriet - VINNEXC
- 2007
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Annan publikation (populärvet., debatt m.m.)abstract
- Fastelaboratoriet är ett VINN Excellence Center för innovation inom Funktionella Produkter. Centret skapades till minne av innovatören Rolf Faste som under många år var verksam vid Stanford University i Kalifornien, USA
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| 21. |
- Palmblad, Jan, et al.
(författare)
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TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders
- 2008
-
Ingår i: International Journal of Medical Sciences. - Lake Haven : Ivyspring international publishers. - 1449-1907. ; 5:2, s. 87-91
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Tidskriftsartikel (refereegranskat)abstract
- Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x10(9)/L. A reduction of platelets to <600 in asymptomatic or <400 x 10(9)/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD.
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| 22. |
- Palmblad, Magnus, et al.
(författare)
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A 9.4 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer : Description and Performance
- 2000
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Ingår i: European journal of mass spectrometry. - 1469-0667 .- 1751-6838. ; 6:3, s. 267-275
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Tidskriftsartikel (refereegranskat)abstract
- 9.4 Tesla Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers (Bruker BioAPEX-94e) have been installed at the Division of Ion Physics, Uppsala University, and at the Department of Chemistry, University of Warwick, The BioAPEX-94e FT-ICR instrument is built around a high-field, superconducting magnet and a platform with easily interchangeable ion sources [matrix-assisted laser desorption/ionisation (MALDI), secondary ion mass spectrometry (SIMS), electrospray ionisation (ESI) and electron impact/chemical ionisation (EI/CI)I. In this paper a technical description of the instrument is given. Outstanding performance characteristics are demonstrated, notably clear resolution of C59N+ and (C58C2+)-C-13 (mass difference 3.65 mDa) and mass measurement accuracy at the low ppm level. A wide range of applications in Warwick and Uppsala is described, demonstrating the versatility and high performance of the instrument.
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| 23. |
- Palmblad, Magnus, et al.
(författare)
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Automatic Analysis of Hydrogen/Deuterium Exchange Mass Spectra of Peptides and Proteins using Calculations of Isotopic Distributions
- 2001
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Ingår i: Journal of the American Society for Mass Spectrometry. - 1044-0305 .- 1879-1123. ; 12:11, s. 1153-1162
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Tidskriftsartikel (refereegranskat)abstract
- High mass-resolving power has been shown to be useful for studying the conformational dynamics of proteins by hydrogen/deuterium (H/D) exchange. A computer algorithm was developed that automatically identifies peptides and their extent of deuterium incorporation from H/D exchange mass spectra of enzymatic digests or fragment ions produced by collisionally induced dissociation (CID) or electron capture dissociation (ECD). The computer algorithm compares measured and calculated isotopic distributions and uses a fast calculation of isotopic distributions using the fast Fourier transform (FFT). The algorithm facilitates rapid and automated analysis of H/D exchange mass spectra suitable for high-throughput approaches to the study of peptide and protein structures. The algorithm also makes the identification independent on comparisons with undeuterated control samples. The applicability of the algorithm was demonstrated on simulated isotopic distributions as well as on experimental data, such as Fourier transform ion cyclotron resonance (FTICR) mass spectra of myoglobin peptic digests, and CID and ECD spectra of substance P.
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| 24. |
- Palmblad, Magnus, et al.
(författare)
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Capillary electrophoresis - A bibliometric analysis
- 2023
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Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier. - 0165-9936 .- 1879-3142. ; 159
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Forskningsöversikt (refereegranskat)abstract
- We have explored the history of the field of capillary electrophoresis using bibliometric methods. The analysis shows that 416 prolific researchers are connected in a single, large, co-authorship network based on publications on capillary electrophoresis between 1980 and 2021, with a few pioneers having remained active throughout much of this time period. Looking at research topics revealed electro-chemistry, sensors, nanotechnology and metabolomics as 'hot' topics, with fundamental method development being more 'mature', and reveal that capillary electrophoresis technology have matured over a 30-year time period, with research efforts moving from separations to quantitative measurements to biomedical applications. The citation patterns showed the strongest coupling between journals of similar scope. Interactive versions of the bibliometric network visualizations are available on-line at https://tinyurl.com/2z7q7wcx (researcher co-authorship network), https://tinyurl.com/2jmhsgxx (research topic network) and https://tinyurl.com/2lnfzzgn (journal bibliographic coupling citation network).(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 25. |
- Palmblad, Magnus, 1973-
(författare)
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Identification and Characterization of Peptides and Proteins using Fourier Transform Ion Cyclotron Resonance Mass Spectrometry
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mass spectrometry has in recent years been established as the standard method for protein identification and characterization in proteomics with excellent intrinsic sensitivity and specificity. Fourier transform ion cyclotron resonance is the mass spectrometric technique that provides the highest resolving power and mass accuracy, increasing the amount of information that can be obtained from complex samples. This thesis concerns how useful information on proteins of interest can be extracted from mass spectrometric data on different levels of protein structure and how to obtain this data experimentally. It was shown that it is possible to analyze complex mixtures of protein tryptic digests by direct infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry and identify abundant proteins by peptide mass fingerprinting. Coupling on-line methods such as liquid chromatography and capillary electrophoresis increased the number of proteins that could be identified in human body fluids. Protein identification was also improved by novel statistical methods utilizing prediction of chromatographic behavior and the non-randomness of enzymatic digestion. To identify proteins by short sequence tags, electron capture dissociation was implemented, improved and finally coupled on-line to liquid chromatography for the first time. The combined techniques can be used to sequence large proteins de novo or to localize and characterize any labile post-translational modification. New computer algorithms for the automated analysis of isotope exchange mass spectra were developed to facilitate the study of protein structural dynamics. The non-covalent interaction between HIV-inhibitory peptides and the oligomerization of amyloid β-peptides were investigated, reporting several new findings with possible relevance for development of anti-HIV drug therapies and understanding of fundamental mechanisms in Alzheimer’s disease.
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| 26. |
- Palmblad, Magnus, et al.
(författare)
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Interpretation of the DOME Recommendations for Machine Learning in Proteomics and Metabolomics
- 2022
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 21:4, s. 1204-1207
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Tidskriftsartikel (refereegranskat)abstract
- Machine learning is increasingly applied in proteomics and metabolomics to predict molecular structure, function, and physicochemical properties, including behavior in chromatography, ion mobility, and tandem mass spectrometry. These must be described in sufficient detail to apply or evaluate the performance of trained models. Here we look at and interpret the recently published and general DOME (Data, Optimization, Model, Evaluation) recommendations for conducting and reporting on machine learning in the specific context of proteomics and metabolomics.
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| 27. |
- Palmblad, Magnus, et al.
(författare)
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Liquid Chromatography and Electron Capture Dissociation in Fourier Transform Ion Cyclotron Resonance Mass Spectrometry
- 2002
-
Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 16:10, s. 988-992
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Tidskriftsartikel (refereegranskat)abstract
- Liquid separation methods in combination with electrospray mass spectrometry as well as the recently introduced fragmentation method electron capture dissociation (ECD) have become powerful tools in proteomics research. This paper presents the results of the first successful attempts to combine liquid chromatography (LC) and Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) with ECD in the analysis of a mixture of standard peptides and of a bovine serum albumin tryptic digest. A novel electron injection system provided conditions for ECD sufficient to yield extensive sequence information for the most abundant peptides in the mixtures on the time-scale of the chromatographic separation. The results suggest that LC/ECD-FTICRMS can be employed in the characterization of peptides in enzymatic digests of proteins or protein mixtures and identify and localize posttranslational modifications.
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| 28. |
- Palmblad, Magnus, et al.
(författare)
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Oxidation of Methionine-35 Attenuates Formation of Amyloid β-Peptide 1-40 Oligomers
- 2002
-
Ingår i: Journal of chemical biology. - 1864-6158 .- 1864-6166. ; 277:22, s. 19506-19510
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid plaques formed by aggregation of the amyloid β-peptide (Aβ) are an intrinsic component of Alzheimer disease pathogenesis. It has been suggested that oxidation of methionine 35 in Aβ has implications for Alzheimer disease, and it has been shown that oxidation of Met-35 significantly inhibits aggregation in vitro. In this study, the aggregational properties of Aβ-(1–40) before and after Met-35 oxidation were investigated using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The results show that Aβ-(1–40)Met-35(O) trimer and tetramer formation is significantly attenuated as compared with Aβ-(1–40). This suggests that oxidation of Met-35 inhibits a conformational switch in Aβ-(1–40) necessary for trimer but not dimer formation. Random incorporation of Aβ-(1–40) and Aβ-(1–40)Met-35(O) in homo- and heterooligomers could also be observed. This is the first report of an early rate-limiting step in Aβ-(1–40) aggregation. Slowing of the fibrillization process at this early step is likely to support prolonged solubility and clearance of Aβ from brain and may reduce disease progression.
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| 29. |
- Palmblad, Magnus, et al.
(författare)
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Prediction of chromatographic retention and protein identification in liquid chromatography/mass spectrometry
- 2002
-
Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 74:22, s. 5826-5830
-
Tidskriftsartikel (refereegranskat)abstract
- Liquid chromatography coupled on- or off-line with mass spectrometry is rapidly advancing as a tool in proteomics capable of dealing with the inherent complexity in biology and complementing conventional approaches based on two-dimensional gel electrophoresis. Proteins can be identified by proteolytic digestion and peptide mass fingerprinting or by searching databases using short-sequence tags generated by tandem mass spectrometry. This paper shows that information on the chromatographic behavior of peptides can assist protein identification by peptide mass fingerprinting in liquid chromatography/mass spectrometry. This additional information is significant and already available at no extra experimental cost.
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| 30. |
- Palmblad, Magnus, et al.
(författare)
-
Protein identification by liquid chromatography-mass spectrometry using retention time prediction
- 2004
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Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 803:1, s. 131-135
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Tidskriftsartikel (refereegranskat)abstract
- Liquid chromatography has been coupled with mass spectrometry to improve the dynamic range and to reduce the complexity of sample introduced to the mass spectrometer at any given time. The chromatographic separation also provides information on the analytes, such as peptides in enzymatic digests of proteins; information that can be used when identifying the proteins by peptide mass fingerprinting. This paper discusses a recently introduced method based on retention time prediction to extract information from chromatographic separations and the applications of this method to protein identification in organisms with small and large genomes.
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| 31. |
- Palmblad, Magnus, et al.
(författare)
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Semantic Annotation of Experimental Methods in Analytical Chemistry
- 2022
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:44, s. 15464-15471
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Tidskriftsartikel (refereegranskat)abstract
- A major obstacle for reusing and integrating existing data is finding the data that is most relevant in a given context. The primary metadata resource is the scientific literature describing the experiments that produced the data. To stimulate the development of natural language processing methods for extracting this information from articles, we have manually annotated 100 recent open access publications in Analytical Chemistry as semantic graphs. We focused on articles mentioning mass spectrometry in their experimental sections, as we are particularly interested in the topic, which is also within the domain of several ontologies and controlled vocabularies. The resulting gold standard dataset is publicly available and directly applicable to validating automated methods for retrieving this metadata from the literature. In the process, we also made a number of observations on the structure and description of experiments and open access publication in this journal.
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| 32. |
- Palmblad, Magnus, et al.
(författare)
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Text mining and computational chemistry reveal trends in applications and applicability of capillary electrophoresis
- 2023
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Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier. - 0165-9936 .- 1879-3142. ; 159
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Forskningsöversikt (refereegranskat)abstract
- Capillary electrophoresis has matured into a highly sensitive and widely applied analytical method over the last forty years. Here we combine text mining and computational chemistry to paint, with very broad strokes, the applicability and trends in the scientific literature on capillary electrophoresis, simulta-neously demonstrating that this is not only possible, but reveal both expected and unexpected details of this history. All software and data are freely available on GitHub (https://github.com/ReinV/SCOPE) and OSF (https://osf.io/e56zt/).
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| 33. |
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| 34. |
- Ramström, Margareta, et al.
(författare)
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Protein identification in cerebrospinal fluid using packed capillary liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry
- 2003
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 3:2, s. 184-190
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Tidskriftsartikel (refereegranskat)abstract
- The identification and characterization of proteins in complex biological samples such as body fluids, require powerful and reliable tools. Mass spectrometry is today one of the most important methods in such research. This paper reports on the results from the first experiment where a tryptic digest of cerebrospinal fluid was analyzed applying reversed phase liquid chromatography coupled on-line to a 9.4 T Fourier transform ion cyclotron resonance mass spectrometer. In total, 70 204 peaks were detected, which originated from 16 296 isotopic clusters corresponding to 6551 unique peptide masses. From these masses, 39 proteins were identified in the sample. The amount of sample required for one experiment corresponds to 32 μL of cerebrospinal fluid.
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| 35. |
- The, Matthew, et al.
(författare)
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A Protein Standard That Emulates Homology for the Characterization of Protein Inference Algorithms
- 2018
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 17:5, s. 1879-1886
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Tidskriftsartikel (refereegranskat)abstract
- A natural way to benchmark the performance of an analytical experimental setup is to use samples of known measured analytes are peptides and not the actual proteins one of the inherent problems of interpreting data is that the composition and see to what degree one can correctly infer the content of such a sample from the data. For shotgun proteomics, themselves. As some proteins share proteolytic peptides, there might be more than one possible causative set of proteins resulting in a given set of peptides and there is a need for mechanisms that infer proteins from lists of detected peptides. A weakness of commercially available samples of known content is that they consist of proteins that are deliberately selected for producing tryptic peptides that are unique to a single protein. Unfortunately, such samples do not expose any complications in protein inference. Hence, for a realistic benchmark of protein inference procedures, there is a need for samples of known content where the present proteins share peptides with known absent proteins. Here, we present such a standard, that is based on E. coli expressed human protein fragments. To illustrate the application of this standard, we benchmark a set of different protein inference procedures on the data. We observe that inference procedures excluding shared peptides provide more accurate estimates of errors compared to methods that include information from shared peptides, while still giving a reasonable performance in terms of the number of identified proteins. We also demonstrate that using a sample of known protein content without proteins with shared tryptic peptides can give a false sense of accuracy for many protein inference methods.
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| 36. |
- Vizcaíno, Juan Antonio, et al.
(författare)
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A community proposal to integrate proteomics activities in ELIXIR
- 2017
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Ingår i: F1000Research. - : F1000 Research Ltd. - 2046-1402. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Computational approaches have been major drivers behind the progress of proteomics in recent years. The aim of this white paper is to provide a framework for integrating computational proteomics into ELIXIR in the near future, and thus to broaden the portfolio of omics technologies supported by this European distributed infrastructure. This white paper is the direct result of a strategy meeting on 'The Future of Proteomics in ELIXIR' that took place in March 2017 in Tübingen (Germany), and involved representatives of eleven ELIXIR nodes. These discussions led to a list of priority areas in computational proteomics that would complement existing activities and close gaps in the portfolio of tools and services offered by ELIXIR so far. We provide some suggestions on how these activities could be integrated into ELIXIR's existing platforms, and how it could lead to a new ELIXIR use case in proteomics. We also highlight connections to the related field of metabolomics, where similar activities are ongoing. This white paper could thus serve as a starting point for the integration of computational proteomics into ELIXIR. Over the next few months we will be working closely with all stakeholders involved, and in particular with other representatives of the proteomics community, to further refine this paper.
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| 37. |
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| 38. |
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