15 results on '"Pulyakhina I"'
Search Results
2. Lactate dehydrogenase from the tetraploid weatherfish Misgurnus fossilis during temperature adaptation: Determination of structural differences in two forms of the enzyme by molecular modeling methods
- Author
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Pulyakhina, I. V. and Ozernyuk, N. D.
- Published
- 2011
- Full Text
- View/download PDF
3. Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis
- Author
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Al-Mossawi, M. H., Chen, L., Fang, H., Ridley, A., de Wit, J., Yager, N., Hammitzsch, A., Pulyakhina, I., Fairfax, B. P., Simone, D., Yi, Yao, Bandyopadhyay, S., Doig, K., Gundle, R, Kendrick, B., Powrie, F., Knight, J. C., and Bowness, P.
- Subjects
Adult ,Aged, 80 and over ,CD4-Positive T-Lymphocytes ,Male ,Science ,Granulocyte-Macrophage Colony-Stimulating Factor ,Middle Aged ,Article ,Receptors, G-Protein-Coupled ,Mice ,Young Adult ,Spondylarthritis ,Animals ,Humans ,Female ,lcsh:Q ,Transcriptome ,lcsh:Science ,Aged ,Genome-Wide Association Study - Abstract
Spondyloarthritis encompasses a group of common inflammatory diseases thought to be driven by IL-17A-secreting type-17 lymphocytes. Here we show increased numbers of GM-CSF-producing CD4 and CD8 lymphocytes in the blood and joints of patients with spondyloarthritis, and increased numbers of IL-17A+GM-CSF+ double-producing CD4, CD8, γδ and NK cells. GM-CSF production in CD4 T cells occurs both independently and in combination with classical Th1 and Th17 cytokines. Type 3 innate lymphoid cells producing predominantly GM-CSF are expanded in synovial tissues from patients with spondyloarthritis. GM-CSF+CD4+ cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GM-CSF+ and IL-17A+GM-CSF+ double-producing CD4 T cells express increased levels of GPR65, a proton-sensing receptor associated with spondyloarthritis in genome-wide association studies and pathogenicity in murine inflammatory disease models. Silencing GPR65 in primary CD4 T cells reduces GM-CSF production. GM-CSF and GPR65 may thus serve as targets for therapeutic intervention of spondyloarthritis., Spondyloarthritis is an inflammatory disease with Th17 cells implicated in the pathogenesis. Here the authors show that patients with spondyloarthritis have increased numbers of GM-CSF-secreting blood and synovial lymphocytes, Th17 or not, that carry a unique transcriptional profile including enhanced GPR65 expression.
- Published
- 2017
4. Annotating Transcriptional Effects of Genetic Variants in Disease-Relevant Tissue: Transcriptome-Wide Allelic Imbalance in Osteoarthritic Cartilage
- Author
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Hollander, W. den, Pulyakhina, I., Boer, C., Bomer, N., Breggen, R. van der, Arindrarto, W., Almeida, R., Lakenberg, N., Sentner, T., Laros, J.F., Hoen, P.A.C. 't, Slagboom, E.P., Nelissen, R., Meurs, J. van, Ramos, Y.F.M., Meulenbelt, I., Hollander, W. den, Pulyakhina, I., Boer, C., Bomer, N., Breggen, R. van der, Arindrarto, W., Almeida, R., Lakenberg, N., Sentner, T., Laros, J.F., Hoen, P.A.C. 't, Slagboom, E.P., Nelissen, R., Meurs, J. van, Ramos, Y.F.M., and Meulenbelt, I.
- Abstract
Contains fulltext : 202683.pdf (publisher's version ) (Open Access), OBJECTIVE: Multiple single-nucleotide polymorphisms (SNPs) conferring susceptibility to osteoarthritis (OA) mark imbalanced expression of positional genes in articular cartilage, reflected by unequally expressed alleles among heterozygotes (allelic imbalance [AI]). We undertook this study to explore the articular cartilage transcriptome from OA patients for AI events to identify putative disease-driving genetic variation. METHODS: AI was assessed in 42 preserved and 5 lesioned OA cartilage samples (from the Research Arthritis and Articular Cartilage study) for which RNA sequencing data were available. The count fraction of the alternative alleles among the alternative and reference alleles together (phi) was determined for heterozygous individuals. A meta-analysis was performed to generate a meta-phi and P value for each SNP with a false discovery rate (FDR) correction for multiple comparisons. To further validate AI events, we explored them as a function of multiple additional OA features. RESULTS: We observed a total of 2,070 SNPs that consistently marked AI of 1,031 unique genes in articular cartilage. Of these genes, 49 were found to be significantly differentially expressed (fold change <0.5 or >2, FDR <0.05) between preserved and paired lesioned cartilage, and 18 had previously been reported to confer susceptibility to OA and/or related phenotypes. Moreover, we identified notable highly significant AI SNPs in the CRLF1, WWP2, and RPS3 genes that were related to multiple OA features. CONCLUSION: We present a framework and resulting data set for researchers in the OA research field to probe for disease-relevant genetic variation that affects gene expression in pivotal disease-affected tissue. This likely includes putative novel compelling OA risk genes such as CRLF1, WWP2, and RPS3.
- Published
- 2019
5. Annotating Transcriptional Effects of Genetic Variants in Disease-Relevant Tissue: Transcriptome-Wide Allelic Imbalance in Osteoarthritic Cartilage
- Author
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den Hollander, W, Pulyakhina, I, de Boer, C, Bomer, N, van der Breggen, R, Arindrarto, W, de Almeida, RC, Lakenberg, N, Sentner, T, Laros, JFJ, 't Hoen, PAC, Slagboom, PE (Eline), Nelissen, R, van Meurs, Joyce, Ramos, YFM, Meulenbelt, I, den Hollander, W, Pulyakhina, I, de Boer, C, Bomer, N, van der Breggen, R, Arindrarto, W, de Almeida, RC, Lakenberg, N, Sentner, T, Laros, JFJ, 't Hoen, PAC, Slagboom, PE (Eline), Nelissen, R, van Meurs, Joyce, Ramos, YFM, and Meulenbelt, I
- Published
- 2019
6. Reproducibility of high-throughput mRNA and small RNA sequencing across laboratories
- Author
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't Hoen PA, Friedlxe4nder MR, Almlxf6f J, Sammeth M, Pulyakhina I, Anvar SY, Laros JF, Buermans HP, Karlberg O, Brxe4nnvall M, GEUVADIS Consortium, den Dunnen JT, van Ommen GJ, Gut IG, Guigxf3 R, Estivill X, Syvxe4nen AC, Dermitzakis ET, Lappalainen T, 't Hoen PA, Friedlxe4nder MR, Almlxf6f J, Sammeth M, Pulyakhina I, Anvar SY, Laros JF, Buermans HP, Karlberg O, Brxe4nnvall M, GEUVADIS Consortium, den Dunnen JT, van Ommen GJ, Gut IG, Guigxf3 R, Estivill X, Syvxe4nen AC, Dermitzakis ET, and Lappalainen T
- Published
- 2013
7. miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis
- Author
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Chen, L, primary, Al-Mossawi, M H, additional, Ridley, A, additional, Sekine, T, additional, Hammitzsch, A, additional, de Wit, J, additional, Simone, D, additional, Shi, H, additional, Penkava, F, additional, Kurowska-Stolarska, M, additional, Pulyakhina, I, additional, Knight, J C, additional, Kim, TJ, additional, and Bowness, P, additional
- Published
- 2016
- Full Text
- View/download PDF
8. Probing the articular cartilage transcriptome for genetic osteoarthritis susceptiblity
- Author
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Hollander, W. den, primary, Pulyakhina, I., additional, Bomer, N., additional, Ramos, Y.F., additional, Breggen, R. van der, additional, Bos, S., additional, Hoen, P-B. A. 't, additional, Slagboom, E.P., additional, Nelissen, R.G., additional, and Meulenbelt, I., additional
- Published
- 2015
- Full Text
- View/download PDF
9. Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis.
- Author
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M.H., Al-Mossawi, Chen, L., Fang, H., Ridley, A., Wit, J. de, Yager, N., Hammitzsch, A., Pulyakhina, I., Fairfax, B. P., Simone, D., Yao Yi, Bandyopadhyay, S., Doig, K., Gundle, R, Kendrick, B., Powrie, F., Knight, J. C., and Bowness, P.
- Subjects
LYMPHOCYTES ,VOXEL-based morphometry ,INNATE lymphoid cells ,T cells ,KILLER cells ,INTERLEUKIN-22 - Abstract
Spondyloarthritis encompasses a group of common inflammatory diseases thought to be driven by IL-17A-secreting type-17 lymphocytes. Here we show increased numbers of GMCSF- producing CD4 and CD8 lymphocytes in the blood and joints of patients with spondyloarthritis, and increased numbers of IL-17A+GM-CSF+ double-producing CD4, CD8, γδ and NK cells. GM-CSF production in CD4 T cells occurs both independently and in combination with classical Th1 and Th17 cytokines. Type 3 innate lymphoid cells producing predominantly GM-CSF are expanded in synovial tissues from patients with spondyloarthritis. GM-CSF+CD4+ cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GM-CSF+ and IL-17A+GM-CSF+ double-producing CD4 T cells express increased levels of GPR65, a proton-sensing receptor associated with spondyloarthritis in genome-wide association studies and pathogenicity in murine inflammatory disease models. Silencing GPR65 in primary CD4 T cells reduces GM-CSF production. GM-CSF and GPR65 may thus serve as targets for therapeutic intervention of spondyloarthritis. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
10. Annotating Transcriptional Effects of Genetic Variants in Disease-Relevant Tissue: Transcriptome-Wide Allelic Imbalance in Osteoarthritic Cartilage.
- Author
-
den Hollander W, Pulyakhina I, Boer C, Bomer N, van der Breggen R, Arindrarto W, Couthino de Almeida R, Lakenberg N, Sentner T, Laros JFJ, 't Hoen PAC, Slagboom EPE, Nelissen RGHH, van Meurs J, Ramos YFM, and Meulenbelt I
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Receptors, Cytokine genetics, Ribosomal Proteins genetics, Risk Factors, Sequence Analysis, RNA, Ubiquitin-Protein Ligases genetics, Allelic Imbalance genetics, Cartilage, Articular metabolism, Osteoarthritis genetics, Polymorphism, Single Nucleotide, Transcriptome genetics
- Abstract
Objective: Multiple single-nucleotide polymorphisms (SNPs) conferring susceptibility to osteoarthritis (OA) mark imbalanced expression of positional genes in articular cartilage, reflected by unequally expressed alleles among heterozygotes (allelic imbalance [AI]). We undertook this study to explore the articular cartilage transcriptome from OA patients for AI events to identify putative disease-driving genetic variation., Methods: AI was assessed in 42 preserved and 5 lesioned OA cartilage samples (from the Research Arthritis and Articular Cartilage study) for which RNA sequencing data were available. The count fraction of the alternative alleles among the alternative and reference alleles together (φ) was determined for heterozygous individuals. A meta-analysis was performed to generate a meta-φ and P value for each SNP with a false discovery rate (FDR) correction for multiple comparisons. To further validate AI events, we explored them as a function of multiple additional OA features., Results: We observed a total of 2,070 SNPs that consistently marked AI of 1,031 unique genes in articular cartilage. Of these genes, 49 were found to be significantly differentially expressed (fold change <0.5 or >2, FDR <0.05) between preserved and paired lesioned cartilage, and 18 had previously been reported to confer susceptibility to OA and/or related phenotypes. Moreover, we identified notable highly significant AI SNPs in the CRLF1, WWP2, and RPS3 genes that were related to multiple OA features., Conclusion: We present a framework and resulting data set for researchers in the OA research field to probe for disease-relevant genetic variation that affects gene expression in pivotal disease-affected tissue. This likely includes putative novel compelling OA risk genes such as CRLF1, WWP2, and RPS3., (© 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)
- Published
- 2019
- Full Text
- View/download PDF
11. Non-sequential and multi-step splicing of the dystrophin transcript.
- Author
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Gazzoli I, Pulyakhina I, Verwey NE, Ariyurek Y, Laros JF, 't Hoen PA, and Aartsma-Rus A
- Subjects
- Cell Line, Computational Biology methods, Gene Library, High-Throughput Nucleotide Sequencing methods, Humans, Sequence Analysis, RNA methods, Dystrophin genetics, RNA Splice Sites, RNA Splicing
- Abstract
The dystrophin protein encoding DMD gene is the longest human gene. The 2.2 Mb long human dystrophin transcript takes 16 hours to be transcribed and is co-transcriptionally spliced. It contains long introns (24 over 10kb long, 5 over 100kb long) and the heterogeneity in intron size makes it an ideal transcript to study different aspects of the human splicing process. Splicing is a complex process and much is unknown regarding the splicing of long introns in human genes. Here, we used ultra-deep transcript sequencing to characterize splicing of the dystrophin transcripts in 3 different human skeletal muscle cell lines, and explored the order of intron removal and multi-step splicing. Coverage and read pair analyses showed that around 40% of the introns were not always removed sequentially. Additionally, for the first time, we report that non-consecutive intron removal resulted in 3 or more joined exons which are flanked by unspliced introns and we defined these joined exons as an exon block. Lastly, computational and experimental data revealed that, for the majority of dystrophin introns, multistep splicing events are used to splice out a single intron. Overall, our data show for the first time in a human transcript, that multi-step intron removal is a general feature of mRNA splicing.
- Published
- 2016
- Full Text
- View/download PDF
12. SplicePie: a novel analytical approach for the detection of alternative, non-sequential and recursive splicing.
- Author
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Pulyakhina I, Gazzoli I, 't Hoen PA, Verwey N, den Dunnen JT, Aartsma-Rus A, and Laros JF
- Published
- 2015
- Full Text
- View/download PDF
13. Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant.
- Author
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van Roosmalen W, Le Dévédec SE, Golani O, Smid M, Pulyakhina I, Timmermans AM, Look MP, Zi D, Pont C, de Graauw M, Naffar-Abu-Amara S, Kirsanova C, Rustici G, Hoen PA, Martens JW, Foekens JA, Geiger B, and van de Water B
- Subjects
- Animals, Bone Neoplasms secondary, Carcinoma, Non-Small-Cell Lung pathology, Cell Adhesion, Cell Movement genetics, Cell Polarity, Female, Focal Adhesions physiology, Gene Expression Regulation, Neoplastic, Genetic Association Studies, Humans, Kaplan-Meier Estimate, Lung Neoplasms pathology, Lung Neoplasms secondary, Mice, NF-kappa B metabolism, Neoplasm Proteins genetics, Nuclear Proteins physiology, Organ Specificity, Prognosis, Protein Serine-Threonine Kinases deficiency, Protein Serine-Threonine Kinases genetics, RNA Interference, RNA, Small Interfering genetics, Breast Neoplasms genetics, Neoplasm Metastasis genetics, Neoplasm Proteins physiology, Protein Serine-Threonine Kinases physiology
- Abstract
Tumor cell migration is a key process for cancer cell dissemination and metastasis that is controlled by signal-mediated cytoskeletal and cell matrix adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases and adhesome- and migration-related proteins to identify genes that affect tumor cell migration speed and persistence. Thirty candidate genes that altered cell migration were validated in live tumor cell migration assays. Eight were associated with metastasis-free survival in breast cancer patients, with integrin β3-binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC-transforming protein 1 (SHC1) being the most predictive. Examination of genes that modulate migration indicated that SRPK1, encoding the splicing factor kinase SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated with poor breast cancer disease outcome and preferential metastasis to the lungs and brain. In 2 independent murine models of breast tumor metastasis, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study provides comprehensive information on the molecular determinants of tumor cell migration and suggests that SRPK1 has potential as a drug target for limiting breast cancer metastasis.
- Published
- 2015
- Full Text
- View/download PDF
14. Determining the quality and complexity of next-generation sequencing data without a reference genome.
- Author
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Anvar SY, Khachatryan L, Vermaat M, van Galen M, Pulyakhina I, Ariyurek Y, Kraaijeveld K, den Dunnen JT, de Knijff P, 't Hoen PA, and Laros JF
- Subjects
- Algorithms, Computational Biology standards, Gene Library, Genome, Human, High-Throughput Nucleotide Sequencing methods, Humans, Sequence Analysis, DNA methods, Software, Computational Biology methods, High-Throughput Nucleotide Sequencing standards, Sequence Analysis, DNA standards
- Abstract
We describe an open-source kPAL package that facilitates an alignment-free assessment of the quality and comparability of sequencing datasets by analyzing k-mer frequencies. We show that kPAL can detect technical artefacts such as high duplication rates, library chimeras, contamination and differences in library preparation protocols. kPAL also successfully captures the complexity and diversity of microbiomes and provides a powerful means to study changes in microbial communities. Together, these features make kPAL an attractive and broadly applicable tool to determine the quality and comparability of sequence libraries even in the absence of a reference sequence. kPAL is freely available at https://github.com/LUMC/kPAL webcite.
- Published
- 2014
- Full Text
- View/download PDF
15. Transcriptome and genome sequencing uncovers functional variation in humans.
- Author
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Lappalainen T, Sammeth M, Friedländer MR, 't Hoen PA, Monlong J, Rivas MA, Gonzàlez-Porta M, Kurbatova N, Griebel T, Ferreira PG, Barann M, Wieland T, Greger L, van Iterson M, Almlöf J, Ribeca P, Pulyakhina I, Esser D, Giger T, Tikhonov A, Sultan M, Bertier G, MacArthur DG, Lek M, Lizano E, Buermans HP, Padioleau I, Schwarzmayr T, Karlberg O, Ongen H, Kilpinen H, Beltran S, Gut M, Kahlem K, Amstislavskiy V, Stegle O, Pirinen M, Montgomery SB, Donnelly P, McCarthy MI, Flicek P, Strom TM, Lehrach H, Schreiber S, Sudbrak R, Carracedo A, Antonarakis SE, Häsler R, Syvänen AC, van Ommen GJ, Brazma A, Meitinger T, Rosenstiel P, Guigó R, Gut IG, Estivill X, and Dermitzakis ET
- Subjects
- Alleles, Cell Line, Transformed, Exons genetics, Gene Expression Profiling, Humans, Polymorphism, Single Nucleotide genetics, Quantitative Trait Loci genetics, RNA, Messenger analysis, RNA, Messenger genetics, Genetic Variation genetics, Genome, Human genetics, High-Throughput Nucleotide Sequencing, Sequence Analysis, RNA, Transcriptome genetics
- Abstract
Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project--the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.
- Published
- 2013
- Full Text
- View/download PDF
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