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Raine, Amanda
Alternative names
Publications (10 of 11) Show all publications
Raine, A., Manlig, E., Wahlberg, P., Syvänen, A.-C. & Nordlund, J. (2017). SPlinted Ligation Adapter Tagging (SPLAT), a novel library preparation method for whole genome bisulphite sequencing. Nucleic Acids Research, 45(6), Article ID e36.
Open this publication in new window or tab >>SPlinted Ligation Adapter Tagging (SPLAT), a novel library preparation method for whole genome bisulphite sequencing
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2017 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 45, no 6, article id e36Article in journal (Refereed) Published
Abstract [en]

Sodium bisulphite treatment of DNA combined with next generation sequencing (NGS) is a powerful combination for the interrogation of genome-wide DNA methylation profiles. Library preparation for whole genome bisulphite sequencing (WGBS) is challenging due to side effects of the bisulphite treatment, which leads to extensive DNA damage. Recently, a new generation of methods for bisulphite sequencing library preparation have been devised. They are based on initial bisulphite treatment of the DNA, followed by adaptor tagging of single stranded DNA fragments, and enable WGBS using low quantities of input DNA. In this study, we present a novel approach for quick and cost effectiveWGBS library preparation that is based on splinted adaptor tagging (SPLAT) of bisulphite-converted single-stranded DNA. Moreover, we validate SPLAT against three commercially available WGBS library preparation techniques, two of which are based on bisulphite treatment prior to adaptor tagging and one is a conventional WGBS method.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-320632 (URN)10.1093/nar/gkw1110 (DOI)000398376200001 ()27899585 (PubMedID)
Funder
Swedish Foundation for Strategic Research , RBc08-008
Available from: 2017-08-14 Created: 2017-08-14 Last updated: 2017-08-14Bibliographically approved
Marincevic-Zuniga, Y., Dahlberg, J., Nilsson, S., Raine, A., Nystedt, S., Lindqvist, C. M., . . . Syvänen, A.-C. (2017). Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles. Journal of Hematology & Oncology, 10, Article ID 148.
Open this publication in new window or tab >>Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles
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2017 (English)In: Journal of Hematology & Oncology, ISSN 1756-8722, E-ISSN 1756-8722, Vol. 10, article id 148Article in journal (Refereed) Published
Abstract [en]

Background: Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. Methods: We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes. Results: We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations. Conclusion: Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.

Keyword
Pediatric acute lymphoblastic leukemia, RNA sequencing, Fusion genes, BCP-ALL, T-ALL, Translocation
National Category
Cancer and Oncology Pediatrics
Identifiers
urn:nbn:se:uu:diva-332658 (URN)10.1186/s13045-017-0515-y (DOI)000408001300001 ()28806978 (PubMedID)
Funder
Swedish Foundation for Strategic Research , RBc08-008Swedish Cancer Society, 130440, 160711Swedish Childhood Cancer Foundation, 11098Swedish Research Council, C0524801, 2016-03691_3
Note

De 2 sista författarna delar sistaförfattarskapet.

Available from: 2017-10-31 Created: 2017-10-31 Last updated: 2018-04-02Bibliographically approved
Lindqvist, C. M., Lundmark, A., Nordlund, J., Freyhult, E., Ekman, D., Almlöf, J. C., . . . Syvänen, A.-C. (2016). Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes. OncoTarget, 7(39), 64071-64088
Open this publication in new window or tab >>Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 39, p. 64071-64088Article in journal (Refereed) Published
Abstract [en]

To characterize the mutational patterns of acute lymphoblastic leukemia (ALL) we performed deep next generation sequencing of 872 cancer genes in 172 diagnostic and 24 relapse samples from 172 pediatric ALL patients. We found an overall greater mutational burden and more driver mutations in T-cell ALL (T-ALL) patients compared to B-cell precursor ALL (BCP-ALL) patients. In addition, the majority of the mutations in T-ALL had occurred in the original leukemic clone, while most of the mutations in BCP-ALL were subclonal. BCP-ALL patients carrying any of the recurrent translocations ETV6-RUNX1, BCR-ABL or TCF3-PBX1 harbored few mutations in driver genes compared to other BCP-ALL patients. Specifically in BCP-ALL, we identified ATRX as a novel putative driver gene and uncovered an association between somatic mutations in the Notch signaling pathway at ALL diagnosis and increased risk of relapse. Furthermore, we identified EP300, ARID1A and SH2B3 as relapse-associated genes. The genes highlighted in our study were frequently involved in epigenetic regulation, associated with germline susceptibility to ALL, and present in minor subclones at diagnosis that became dominant at relapse. We observed a high degree of clonal heterogeneity and evolution between diagnosis and relapse in both BCP-ALL and T-ALL, which could have implications for the treatment efficiency.

Keyword
acute lymphoblastic leukemia, targeted next generation sequencing, somatic mutation, relapse, clonal evolution
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-310028 (URN)10.18632/oncotarget.11773 (DOI)000387167800099 ()27590521 (PubMedID)
Funder
Swedish Foundation for Strategic Research , RBc08-08Swedish Cancer Society, CAN 2013/504Swedish Childhood Cancer Foundation, PR2014-0100Swedish Research Council, C0524801Knut and Alice Wallenberg Foundation
Available from: 2016-12-12 Created: 2016-12-09 Last updated: 2018-01-13Bibliographically approved
Wahlberg, P., Lundmark, A., Nordlund, J., Busche, S., Raine, A., Tandre, K., . . . Syvänen, A.-C. (2016). DNA methylome analysis of acute lymphoblastic leukemia cells reveals stochastic de novo DNA methylation in CpG islands. Epigenomics, 8(10), 1367-1387
Open this publication in new window or tab >>DNA methylome analysis of acute lymphoblastic leukemia cells reveals stochastic de novo DNA methylation in CpG islands
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2016 (English)In: Epigenomics, ISSN 1750-1911, Vol. 8, no 10, p. 1367-1387Article in journal (Refereed) Published
Abstract [en]

Aim: To identify regions of aberrant DNA methylation in acute lymphoblastic leukemia (ALL) cells of different subtypes on a genome-wide scale. Materials & methods: Whole-genome bisulfite sequencing (WGBS) was used to determine the DNA methylation levels in cells from four pediatric ALL patients of different subtypes. The findings were confirmed by 450k DNA methylation arrays in a large patient set. Results: Compared with mature B or T cells WGBS detected on average 82,000 differentially methylated regions per patient. Differentially methylated regions are enriched to CpG poor regions, active enhancers and transcriptional start sites. We also identified approximately 8000 CpG islands with variable intermediate DNA methylation that seems to occur as a result of stochastic de novo methylation. Conclusion: WGBS provides an unbiased view and novel insights into the DNA methylome of ALL cells.

Keyword
acute lymphoblastic leukemia, CpG islands, DNA methylation, epigenome, methylome, whole-genome bisulfite sequencing
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-308929 (URN)10.2217/epi-2016-0052 (DOI)000385653900006 ()27552300 (PubMedID)
Funder
Swedish Foundation for Strategic Research , RBc08-008Swedish Cancer Society, 140581Swedish Childhood Cancer Foundation, PR2014-0100Swedish Research Council, C0524801;259-2012-23Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Research Council FormasVINNOVA
Available from: 2016-12-01 Created: 2016-12-01 Last updated: 2018-01-13Bibliographically approved
Roshanbin, S., Lindberg, F., Lekholm, E., Perland, E., Eriksson, M., Åhlund, J., . . . Fredriksson, R. (2016). Histological characterization of orphan transporter MCT14 (SLC16A14) shows abundant expression in mouse CNS and kidney. BMC neuroscience (Online), 17, Article ID 43.
Open this publication in new window or tab >>Histological characterization of orphan transporter MCT14 (SLC16A14) shows abundant expression in mouse CNS and kidney
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2016 (English)In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 17, article id 43Article in journal (Refereed) Published
Abstract [en]

Background: MCT14 (SLC16A14) is an orphan member of the monocarboxylate transporter (MCT) family, also known as the SLC16 family of secondary active transmembrane transporters. Available expression data for this transporter is limited, and in this paper we aim to characterize MCT14 with respect to tissue distribution and cellular localization in mouse brain. Results: Using qPCR, we found that Slc16a14 mRNA was highly abundant in mouse kidney and moderately in central nervous system, testis, uterus and liver. Using immunohistochemistry and in situ hybridization, we determined that MCT14 was highly expressed in excitatory and inhibitory neurons as well as epithelial cells in the mouse brain. The expression was exclusively localized to the soma of neurons. Furthermore, we showed with our phylogenetic analysis that MCT14 most closely relate to the aromatic amino acid- and thyroid-hormone transporters MCT8 (SLC16A2) and MCT10 (SLC16A10), in addition to the carnitine transporter MCT9 (SLC16A9). Conclusions: We provide here the first histological mapping of MCT14 in the brain and our data are consistent with the hypothesis that MCT14 is a neuronal aromatic-amino-acid transporter.

Keyword
Monocarboxylate; Transporter; Mouse; Amino acid
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-282951 (URN)10.1186/s12868-016-0274-7 (DOI)000379823100001 ()27364523 (PubMedID)
Funder
Swedish Research CouncilThe Swedish Brain FoundationSwedish Society for Medical Research (SSMF)Novo Nordisk
Available from: 2016-04-10 Created: 2016-04-08 Last updated: 2017-11-30Bibliographically approved
Lindqvist, C. M., Nordlund, J., Ekman, D., Johansson, A., Moghadam, B. T., Raine, A., . . . Berglund, E. C. (2015). The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing. Human Mutation, 36(1), 118-128
Open this publication in new window or tab >>The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
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2015 (English)In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 36, no 1, p. 118-128Article in journal (Refereed) Published
Abstract [en]

Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.

National Category
Medical Genetics Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-238183 (URN)10.1002/humu.22719 (DOI)000347076700016 ()25355294 (PubMedID)
Available from: 2014-12-10 Created: 2014-12-10 Last updated: 2018-01-11Bibliographically approved
Roshanbin, S., Hellsten, S. V., Tafreshiha, A., Zhu, Y., Raine, A. & Fredriksson, R. (2014). PAT4 is abundantly expressed in excitatory and inhibitory neurons as well as epithelial cells. Brain Research, 1557, 12-25
Open this publication in new window or tab >>PAT4 is abundantly expressed in excitatory and inhibitory neurons as well as epithelial cells
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2014 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1557, p. 12-25Article in journal (Refereed) Published
Abstract [en]

PAT4, the fourth member of the SLC36/proton dependent amino acid transporter (PAT) family, is a high-affinity, low capacity electroneutral transporter of neutral amino acids like proline and tryptophan. It has also been associated with the function of mTORC1, a complex in the mammalian target of rapamycin (mTOR) pathway. We performed in situ hybridization and immunohistological analysis to determine the expression profile of PAT4, as well as an RT-PCR study on tissue from mice exposed to leucine. We performed a phylogenetic analysis to determine the evolutionary origin of PAT4. The in situ hybridization and the immunohistochemistry on mouse brain sections and hypothalamic cells showed abundant PAT4 expression in the mouse brain intracellularly in both inhibitory and excitatory neurons, partially co-localizing with lysosomal markers and epithelial cells lining the ventricles. Its location in epithelial cells around the ventricles indicates a transport of substrates across the blood brain barrier. Phylogenetic analysis showed that PAT4 belongs to an evolutionary old family most likely predating animals, and PAT4 is the oldest member of that family.

National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-220143 (URN)10.1016/j.brainres.2014.02.014 (DOI)000334081800002 ()24530433 (PubMedID)
Available from: 2014-03-11 Created: 2014-03-11 Last updated: 2017-12-05Bibliographically approved
Raine, A., Ivanova, N., Wikberg, J. E. & Ehrenberg, M. (2004). Simultaneous binding of trigger factor and signal recognition particle to the E. coli ribosome.. Biochimie, 86(7), 495-500
Open this publication in new window or tab >>Simultaneous binding of trigger factor and signal recognition particle to the E. coli ribosome.
2004 (English)In: Biochimie, ISSN 0300-9084, Vol. 86, no 7, p. 495-500Article in journal (Other scientific) Published
Keyword
Binding Sites, Carbon Radioisotopes, Escherichia coli/enzymology/genetics/*metabolism, Escherichia coli Proteins/*metabolism, Kinetics, Peptidylprolyl Isomerase/*metabolism, Protein Biosynthesis, Research Support; Non-U.S. Gov't, Ribosomes/*metabolism, Signal Recognition Particle/*metabolism
Identifiers
urn:nbn:se:uu:diva-72391 (URN)15308339 (PubMedID)
Available from: 2005-08-29 Created: 2005-08-29 Last updated: 2011-01-12
Ullers, R. S., Houben, E. N., Raine, A., ten Hagen-Jongman, C. M., Ehrenberg, M., Brunner, J., . . . Luirink, J. (2003). Interplay of signal recognition particle and trigger factor at L23 near the nascent chain exit site on the Escherichia coli ribosome. J. Cell Biology, 161, 679-684
Open this publication in new window or tab >>Interplay of signal recognition particle and trigger factor at L23 near the nascent chain exit site on the Escherichia coli ribosome
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2003 (English)In: J. Cell Biology, Vol. 161, p. 679-684Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-48639 (URN)
Available from: 2008-04-03 Created: 2008-04-03 Last updated: 2011-01-13
Raine, A., Ullers, R., Pavlov, M., Luirink, J., Wikberg, J. E. & Ehrenberg, M. (2003). Targeting and insertion of heterologous membrane proteins in E. coli. Biochimie, 85, 659-668
Open this publication in new window or tab >>Targeting and insertion of heterologous membrane proteins in E. coli
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2003 (English)In: Biochimie, Vol. 85, p. 659-668Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-48636 (URN)
Available from: 2008-04-03 Created: 2008-04-03 Last updated: 2011-01-13
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