| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Rojas-Macias, Miguel A., 1979, et al.
(author)
-
Towards a standardized bioinformatics infrastructure for N- and O-glycomics
- 2019
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Journal article (peer-reviewed)abstract
- The mass spectrometry (MS)-based analysis of free polysaccharides and glycans released from proteins, lipids and proteoglycans increasingly relies on databases and software. Here, we review progress in the bioinformatics analysis of protein-released N- and O-linked glycans (N-and O-glycomics) and propose an e-infrastructure to overcome current deficits in data and experimental transparency. This workflow enables the standardized submission of MS-based glycomics information into the public repository UniCarb-DR. It implements the MIRAGE (Minimum Requirement for A Glycomics Experiment) reporting guidelines, storage of unprocessed MS data in the GlycoPOST repository and glycan structure registration using the GlyTouCan registry, thereby supporting the development and extension of a glycan structure knowledgebase.
|
|
| 6. |
- Braekeveldt, N., et al.
(author)
-
Patient-Derived Xenograft Models Reveal Intratumor Heterogeneity and Temporal Stability in Neuroblastoma
- 2018
-
In: Cancer Research. - 0008-5472. ; 78:20, s. 5958-5969
-
Journal article (peer-reviewed)abstract
- Patient-derived xenografts (PDX) and the Avatar, a single PDX mirroring an individual patient, are emerging tools in preclinical cancer research. However, the consequences of intratumor heterogeneity for PDX modeling of biomarkers, target identification, and treatment decisions remain under-explored. In this study, we undertook serial passaging and comprehensive molecular analysis of neuroblastoma orthotopic PDXs, which revealed strong intrinsic genetic, transcriptional, and phenotypic stability for more than 2 years. The PDXs showed preserved neuroblastoma-associated gene signatures that correlated with poor clinical outcome in a large cohort of patients with neuroblastoma. Furthermore, we captured spatial intratumor heterogeneity using ten PDXs from a single high-risk patient tumor. We observed diverse growth rates, transcriptional, proteomic, and phosphoproteomic profiles. PDX-derived transcriptional profiles were associated with diverse clinical characteristics in patients with high-risk neuroblastoma. These data suggest that high-risk neuroblastoma contains elements of both temporal stability and spatial intratumor heterogeneity, the latter of which complicates clinical translation of personalized PDX-Avatar studies into preclinical cancer research. Significance: These findings underpin the complexity of PDX modeling as a means to advance translational applications against neuroblastoma. (C) 2018 AACR.
|
|
| 7. |
- Levander, S, et al.
(author)
-
Immune-mediated effects targeting hepatitis C virus in a syngeneic replicon cell transplantation mouse model
- 2018
-
In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:8, s. 1525-1535
-
Journal article (peer-reviewed)abstract
- HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells.DesignA total of 5 million H-2b positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2b-restricted mice. Kinetics of tumour growth, HCV RNA replication levels and HCV-specific immune responses were monitored. For immune monitoring, new H-2b-restricted cytotoxic T cell epitopes within the gt2a NS3/4A region were mapped. Immune mice were generated by DNA-based vaccination.ResultsHCV replicon and NS3/4A hepatoma cells generated solid tumours in vivo. Similar to what is seen in human HCV infection did HCV RNA replicate in the presence of inflammation. NS3/4A-specific CD8+ T cells seemed to transiently reduce HCV RNA levels. Both CD4+ and CD8+ T cells were required for protection against tumour growth. Vaccine-induced NS3/4A(gt2a)-specific T cells protected against HCV replicon tumours in wild-type, but not in HCV NS3/4A(gt1a)-transgenic mice with dysfunctional HCV-specific T cells. Importantly, as in human HCV infection, HCV replicon cells neither primed nor boosted a strong NS3/4A-specific T cell response.ConclusionSyngeneic transplantation of mouse HCV replicon cells into immune-competent animals mirrors many in vivo events in humans. This system is versatile and can be applied to any genetically modified H-2b-restricted mouse strain.
|
|
| 8. |
- Lindblad, O, et al.
(author)
-
Aberrant activation of the PI3K/mTOR pathway promotes resistance to sorafenib in AML
- 2016
-
In: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 35:39, s. 5119-5131
-
Journal article (peer-reviewed)abstract
- Therapy directed against oncogenic FLT3 has been shown to induce response in patients with acute myeloid leukemia (AML), but these responses are almost always transient. To address the mechanism of FLT3 inhibitor resistance, we generated two resistant AML cell lines by sustained treatment with the FLT3 inhibitor sorafenib. Parental cell lines carry the FLT3-ITD (tandem duplication) mutation and are highly responsive to FLT3 inhibitors, whereas resistant cell lines display resistance to multiple FLT3 inhibitors. Sanger sequencing and protein mass-spectrometry did not identify any acquired mutations in FLT3 in the resistant cells. Moreover, sorafenib treatment effectively blocked FLT3 activation in resistant cells, whereas it was unable to block colony formation or cell survival, suggesting that the resistant cells are no longer FLT3 dependent. Gene expression analysis of sensitive and resistant cell lines, as well as of blasts from patients with sorafenib-resistant AML, suggested an enrichment of the PI3K/mTOR pathway in the resistant phenotype, which was further supported by next-generation sequencing and phospho-specific-antibody array analysis. Furthermore, a selective PI3K/mTOR inhibitor, gedatolisib, efficiently blocked proliferation, colony and tumor formation, and induced apoptosis in resistant cell lines. Gedatolisib significantly extended survival of mice in a sorafenib-resistant AML patient-derived xenograft model. Taken together, our data suggest that aberrant activation of the PI3K/mTOR pathway in FLT3-ITD-dependent AML results in resistance to drugs targeting FLT3.Oncogene advance online publication, 21 March 2016; doi:10.1038/onc.2016.41.
|
|
| 9. |
- Löfgren, Håkan, et al.
(author)
-
Reduced pain after surgery for cervical disc protrusion/stenosis : A 2 year clinical follow-up
- 2003
-
In: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 25:18, s. 1033-1043
-
Journal article (peer-reviewed)abstract
- Purpose: To follow the clinical outcome after surgery for cervical radiculopathy caused by degenerative cervical disc disease and to compare it with the outcome after conservative treatment.Method: Forty-three patients all awaiting surgery were studied prospectively. A control group of 39 conservatively treated patients were chosen, matched for gender and age. All patients rated their Sickness Impact Profile (SIP) and pain (VAS) and were clinically examined by unbiased observers initially and after 3, 9 and 24 months.Results: Long-lasting pain reduction was noted both in the neck and in the arm for the operated patients, as well as improved sensory function and reduction of reflex disturbances. Their SIP showed a temporary improvement in the overall index, in the psychosocial dimension, in sleep/rest and home management, but only mobility remained improved. Among the operated patients referred directly to us, there was an improvement in SIP at the final follow-up. The control group's SIP indicated only a temporary improvement in sleep/rest.Conclusions: Surgically treated patients experienced pain reduction which was partially maintained for at least 24 months. A sustained improvement in the health status measured by SIP was observed only among operated patients that were not referred via the social insurance offices.
|
|
| 10. |
|
|
| 11. |
- Michel, Steven F., et al.
(author)
-
Using the HCR-20 to Predict Aggressive Behavior among Men with Schizophrenia Living in the Community: Accuracy of Prediction, General and Forensic Settings, and Dynamic Risk Factors
- 2013
-
In: International Journal of Forensic Mental Health. - : Informa UK Limited. - 1932-9903 .- 1499-9013. ; 12:1, s. 1-13
-
Journal article (peer-reviewed)abstract
- The HCR-20 is widely used to assess risk of violence among patients with schizophrenia. Further understanding of the accuracy and changes over time in C and R scores is needed. Using prospectively collected data on 248 men with schizophrenia, the present study found that the HCR-20 significantly predicted aggressive behavior over 24 months. The H, C, R, HCR-20 total, and final risk judgment scores were unable to predict aggressive behavior better than chance among the general psychiatric patients in the first six months after discharge. Changes in three C items, the total R score, and in three R items significantly predicted changes in aggressive behavior.
|
|
| 12. |
- Resjö, Svante, et al.
(author)
-
Quantitative Label-Free Phosphoproteomics of Six Different Life Stages of the Late Blight Pathogen Phytophthora infestans Reveals Abundant Phosphorylation of Members of the CRN Effector Family
- 2014
-
In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:4, s. 1848-1859
-
Journal article (peer-reviewed)abstract
- The oomycete Phytophthora infestans is the causal agent of late blight in potato and tomato. Since the underlying processes that govern pathogenicity and development in P. infestans are largely unknown, we have performed a large-scale phosphoproteomics study of six different P. infestans life stages. We have obtained quantitative data for 2922 phosphopeptides and compared their abundance. Life-stages-pecific phosphopeptides include ATP-binding cassette transporters and a kinase that only occurs in appressoria. In an extended data set, we identified 2179 phosphorylation sites and deduced 22 phosphomotifs. Several of the phosphomotifs matched consensus sequences of kinases that occur in P. infestans but not Arabidopsis. In addition, we detected tyrosine phosphopeptides that are potential targets of kinases resembling mammalian tyrosine kinases. Among the phosphorylated proteins are members of the RXLR and Crinkler effector families. The latter are phosphorylated in several life stages and at multiple positions, in sites that are conserved between different members of the Crinkler family. This indicates that proteins in the Crinkler family have functions beyond their putative role as (necrosis-inducing) effectors. This phosphoproteomics data will be instrumental for studies on oomycetes and host oomycete interactions. The data sets have been deposited to ProteomeXchange (identifier PXD000433).
|
|
| 13. |
|
|
| 14. |
- Teleman, Johan, et al.
(author)
-
Numerical compression schemes for proteomics mass spectrometry data.
- 2014
-
In: Molecular & Cellular Proteomics. - 1535-9484. ; 13:6, s. 1537-1542
-
Journal article (peer-reviewed)abstract
- The open XML format mzML, used for representation of mass spectrometry (MS) data, is pivotal for the development of platform-independent MS analysis software. Although conversion from vendor formats to mzML must take place on a platform on which the vendor libraries are available (i.e. Windows), once mzML files have been generated, they can be used on any platform. However, the mzML format has turned out to be less efficient than vendor formats. In many cases, the naive mzML representation is 4-fold or even up to 18-fold larger compared to the original vendor file. In disk I/O limited setups, a larger data file also leads to longer processing times, which is a problem given the data production rates of modern mass spectrometers. In an attempt to reduce this problem, we here present a family of numerical compression algorithms called MS-Numpress, intended for efficient compression of MS data. To facilitate ease of adoption, the algorithms target the binary data in the mzML standard, and support in main proteomics tools is already available. Using a test set of 10 representative MS data files we demonstrate typical file size decreases of 90% when combined with traditional compression, as well as read time decreases of up to 50%. It is envisaged that these improvements will be beneficial for data handling within the MS community.
|
|
| 15. |
- Willforss, J, et al.
(author)
-
Interactive proteogenomic exploration of response to Fusarium head blight in oat varieties with different resistance
- 2020
-
In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 218, s. 103688-103688
-
Journal article (peer-reviewed)abstract
- Fusarium species are cereal pathogens that cause the Fusarium Head Blight (FHB) disease. FHB can reduce yield, cause mycotoxin accumulation in the grain and reduce germination efficiency of the harvested seeds. Understanding the biochemical interactions between the host plants and the pathogen is crucial for controlling the disease and for the development of cultivars with improved tolerance to FHB. Here, we studied morphological and proteomic differences between the susceptible oat variety Belinda and the more resistant variety Argamak using variety-specific transcriptome assemblies as references. Measurements of deoxynivalenol toxin levels confirmed the partial resistance in Argamak and the susceptibility in Belinda. To jointly investigate the proteomics- and sequence data, we developed an RShiny-based interface for interactive exploration of the dataset using univariate and multivariate statistics. When applying this interface to the dataset, quantitative protein differences between Belinda and Argamak were detected, and eighteen peptides were found uniquely in Argamak during infection, among them several lipoxygenases. Such proteins can be developed as markers for Fusarium resistance breeding. In conclusion, this study provides the first proteogenomic insight on molecular Fusarium-oat interactions at both morphological and molecular levels and the data are openly available through an interactive interface for further inspection. SIGNIFICANCE: Fusarium head blight causes widespread damage to crops, and chronic and acute toxicity to human and livestock due to the accumulation of toxins during infection. In the present study, two oat varieties with differing resistance were challenged with Fusarium to understand the disease better, and studied both at morphological and molecular levels, identifying proteins which could play a role in the defense mechanism. Furthermore, a proteogenomics approach allows joint profiling of expression and sequence level differences to identify potentially functionally differing mutations. Here such analysis is made openly available through an interactive interface which allows other scientists to draw further findings from the data. This study may both serve as a basis for understanding oat disease response and developing breeding markers for Fusarium resistant oat and future proteogenomic studies using the interactive approach described.
|
|
| 16. |
- Willforss, J., et al.
(author)
-
Stable bull fertility protein markers in seminal plasma
- 2021
-
In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 236
-
Journal article (peer-reviewed)abstract
- Bull fertility is an important trait in breeding as the semen of one bull can, potentially, be used to perform thousands of inseminations. The high number of inseminations needed to obtain reliable measures from Non-Return Rates to oestrus creates difficulties in assessing fertility accurately. Improving molecular knowledge of seminal properties may provide ways to facilitate selection of bulls with good semen quality. In this study, liquid chromatography mass spectrometry (LC-MS/MS) was used to analyze the protein content from the seminal plasma of 20 bulls with Non-Return Rates between 35 and 60%, sampled across three seasons. Overall, 1343 proteins were identified and proteins with consistent correlation to fertility across multiple seasons found. From these, nine protein groups had a significant Pearson correlation (p < 0.1) with fertility in all three seasons and 34 protein groups had a similar correlation in at least two seasons. Among notable proteins showing a high and consistent correlation across seasons were Osteopontin, a lipase (LIPA) and N-acetylglucosamine-1phosphotransferase subunit gamma. Three proteins were combined in a multiple linear regression to predict fertility (r = 0.81). These sets of proteins represent potential markers, which could be used by the breeding industry to phenotype bull fertility. Significance: The ability of bull spermatozoa to fertilize oocytes is crucial for breeding efficiency. However, the reliability of this trait from field measures is relatively low and the prediction of fertility given by conventional methods to evaluate sperm quality is currently not very accurate. In this work, we identify sets of proteins in bull seminal plasma from repeated samples collected at different times of the year that correlate to fertility in a consistent way. We combined these individual proteins to build a molecular signature predictive of fertility. This study provides an overview of proteins linked to fertility in seminal plasma, thereby increasing knowledge of the bull seminal plasma proteome. Protein signatures from the latter, potentially related to fertility, may be of use to predict fertility for individual bulls.
|
|
