his.sePublications
Change search
Refine search result
1 - 29 of 29
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Adamovic, Tatjana
    et al.
    Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA.
    Hamta, Achmad
    Univ Gothenburg, CMB Genet, Gothenburg, Sweden.
    Roshani, Leyla
    Univ Gothenburg, CMB Genet, Gothenburg, Sweden.
    Lü, Xuschun
    Univ Gothenburg, CMB Genet, Gothenburg, Sweden.
    Röhme, Dan
    Univ Gothenburg, CMB Genet, Gothenburg, Sweden.
    Helou, Khalil
    Univ Gothenburg, Dept Oncol, Gothenburg, Sweden.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Levan, Göran
    Univ Gothenburg, CMB Genet, Gothenburg, Sweden.
    Rearrangement and allelic imbalance on chromosome 5 leads to homozygous deletions in the CDKN2A/2B tumor suppressor gene region in rat endometrial cancer2008In: Cancer Genetics and Cytogenetics, ISSN 2210-7762, E-ISSN 2210-7770, Vol. 184, no 1, p. 9-21Article in journal (Refereed)
    Abstract [en]

    The inbred BDII rat is a valuable experimental model for the genetic analysis of hormone-dependent endometrial adenocarcinoma (EAC). One common aberration detected previously by comparative genomic hybridization in rat EAC is loss affecting mostly the middle part of rat chromosome 5 (RNO5). First, we applied an RNO5-specific painting probe and four region-specific gene probes onto tumor cell metaphases from 21 EACs, and found that rearrangements involving RNO5 were common. The copy numbers of loci situated on RNO5 were found to be reduced, particularly for the CDKN2A/2B locus. Second, polymerase chain reaction analysis was performed with 22 genes and markers and homozygous deletions of the CDKN2A exon 1β and CDKN2B genes were detected in 13 EACs (62%) and of CDKN2A exon 1α in 12 EACs (57%) Third, the occurrence of allelic imbalance in RNO5 was analyzed using 39 microsatellite markers covering the entire chromosome and frequent loss of heterozygosity was detected. Even more intriguing was the repeated finding of allele switching in a narrow region of 7 Mb across the CDKN2A/2B locus. We conclude that genetic events affecting the middle part of RNO5 (including bands 5q31q33 and the CDKN2A locus) contribute to the development of EAC in rat, with the CDKN2A locus having a primary role.

  • 2.
    Behboudi, A.
    et al.
    Univ Gothenburg, Inst Biomed, Gothenburg, Sweden.
    Nordlander, C.
    Univ Gothenburg, Inst Cell & Mol Biol, Gothenburg, Sweden.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Karlsson, S.
    Evidence for a tumor suppressor locus distal to Tp53 - a study in experimental endometrial adenocarcinoma2007In: European Journal of Cancer Supplements, ISSN 1359-6349, E-ISSN 1878-1217, Vol. 5, no 4, p. 62-62Article in journal (Other academic)
  • 3.
    Carlsson, Jessica
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Davidsson, Sabina
    Orebro Univ Hosp, Dept Urol, Orebro, Sweden / Univ Orebro, Sch Hlth & Med Sci, Orebro, Sweden.
    Helenius, Gisela
    Orebro Univ Hosp, Dept Lab Med, Orebro, Sweden.
    Karlsson, Mats
    Orebro Univ Hosp, Dept Lab Med, Orebro, Sweden.
    Lubovac, Zelmina
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Andren, Ove
    Orebro Univ Hosp, Dept Urol, Orebro, Sweden .
    Olsson, Björn
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    A miRNA expression signature that separates between normal and malignant prostate tissues2011In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 11, p. 14-Article in journal (Refereed)
    Abstract [en]

    Background: MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that post-transcriptionally regulate genes involved in several key biological processes and thus are involved in various diseases, including cancer. In this study we aimed to identify a miRNA expression signature that could be used to separate between normal and malignant prostate tissues. Results: Nine miRNAs were found to be differentially expressed (p < 0.00001). With the exception of two samples, this expression signature could be used to separate between the normal and malignant tissues. A cross-validation procedure confirmed the generality of this expression signature. We also identified 16 miRNAs that possibly could be used as a complement to current methods for grading of prostate tumor tissues. Conclusions: We found an expression signature based on nine differentially expressed miRNAs that with high accuracy (85%) could classify the normal and malignant prostate tissues in patients from the Swedish Watchful Waiting cohort. The results show that there are significant differences in miRNA expression between normal and malignant prostate tissue, indicating that these small RNA molecules might be important in the biogenesis of prostate cancer and potentially useful for clinical diagnosis of the disease.

  • 4.
    Carlsson, Jessica
    et al.
    Örebro University / Örebro University Hospital.
    Helenius, Gisela
    Örebro University / Örebro University Hospital.
    Karlsson, Mats G.
    Örebro University / Örebro University Hospital.
    Andrén, Ove
    Örebro University / Örebro University Hospital.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate2013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, article id 362Article in journal (Refereed)
    Abstract [en]

    Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate. Methods: Patients with prostate cancer were included in the study if they had a tumor with Gleason grade 3 in the PZ, the TZ, or both (n=16). Normal prostate tissue was collected from men undergoing cystoprostatectomy (n=20). The expression of 667 unique miRNAs was investigated using TaqMan low density arrays for miRNAs. Student's t-test was used in order to identify differentially expressed miRNAs, followed by hierarchical clustering and principal component analysis (PCA) to study the separation of the tissues. The ADtree algorithm was used to identify markers for classification of tissues and a cross-validation procedure was used to test the generality of the identified miRNA-based classifiers. Results: The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified. Conclusions: The results of this study indicate that the major differences in the transcription program are those arising during tumor development, rather than during normal tissue development. In addition, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the different zones. MicroRNA signatures that are specific for PZ and TZ tumors could also lead to more accurate prognoses, since tumors arising in the PZ tend to be more aggressive than tumors arising in the TZ.

  • 5.
    Carlsson, Jessica
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Helenius, Gisela
    Örebro University Hospital.
    Karlsson, Mats
    Örebro University Hospital.
    Lubovac, Zelmina
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Andrén, Ove
    Örebro University Hospital.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Klinga-Levan, Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Validation of suitable endogenous control genes for expression studies of miRNA in prostate cancer tissues2010In: Cancer Genetics and Cytogenetics, ISSN 2210-7762, E-ISSN 2210-7770, Vol. 202, no 2, p. 71-75Article in journal (Refereed)
    Abstract [en]

    When performing quantitative polymerase chain reaction analysis, there is a need for correction of technical variation between experiments. This correction is most commonly performed by using endogenous control genes, which are stably expressed across samples, as reference genes for normal expression in a specific tissue. In microRNA (miRNA) studies, two types of control genes are commonly used: small nuclear RNAs and small nucleolar RNAs. In this study, six different endogenous control genes for miRNA studies were investigated in prostate tissue material from the Swedish Watchful Waiting cohort. The stability of the controls was investigated using two different software applications, NormFinder and BestKeeper. RNU24 was the most suitable endogenous control gene for miRNA studies in prostate tissue materials.

  • 6.
    Chen, Lei
    et al.
    University of Skövde, School of Humanities and Informatics.
    Nordlander, Carola
    CMB-Genetics, Lundberg Laboratory, Göteborg University, Göteborg, Sweden.
    Behboudi, Afrouz
    CMB-Genetics, Lundberg Laboratory, Göteborg University, Göteborg, Sweden.
    Olsson, Björn
    University of Skövde, School of Humanities and Informatics.
    Klinga Levan, Karin
    University of Skövde, School of Life Sciences.
    Deriving evolutionary tree models of the oncogenesis of endometrial adenocarcinoma2007In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 120, no 2, p. 292-296Article in journal (Refereed)
    Abstract [en]

    Endometrial adenocarcinoma (EAC) is the fourth leading cause of cancer death in women worldwide, but not much is known about the underlying genetic factors involved in the development of this complex disease. In the present work, we used 3 different algorithms to derive tree models of EAC oncogenesis from data on the frequencies of genomic alterations in rat chromosome 10 (RNO10). The tumor material was derived from progenies of crosses between the EAC susceptible BDII inbred rat strain and two non susceptible inbred rat strains. Data from allelic imbalance scans of RNO10 with microsatellite markers on solid tumor material and corresponding tissue cultures were used. For the analysis, RNO10 was divided into 24 segments containing a total of 59 informative microsatellite markers. The derived tree models show that genomic alterations have occurred in 11 of the 24 segments. In addition, the models provide information about the likely order of the alterations as well as their relationship with each other. Interestingly, there was a high degree of consistency among the different tree models and with the results of previous-studies, which supports the reliability of the tree models. Our results may be extended into a general approach for tree modeling of whole genome alterations during oncogenesis. (c) 2006 Wiley-Liss, Inc.

  • 7.
    Fagerlind, Magnus
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Stålhammar, Hans
    VikingGenetics, Skara.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Klinga-Levan, Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Expression of miRNAs in Bull Spermatozoa Correlates with Fertility Rates2015In: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531, Vol. 50, no 4, p. 587-594Article in journal (Refereed)
  • 8.
    Falck, Eva
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Behboudi, Afrouz
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    The impact of the genetic background on the genome make-up of tumor cells2012In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 51, no 5, p. 438-446Article in journal (Refereed)
    Abstract [en]

    Endometrial adenocarcinoma (EAC) is the most common form of malignancy in the female genital tract, ranking as the fourth leading form of invasive tumors that affect women. The BDII inbred rat strain has been used as a powerful tumor model in studies of the genetic background of EAC. Females from the BDII strain are prone to develop tumors with an incidence of more than 90%. Development of EAC in BDII female rats has similarities in pathogenesis, histopathological, and molecular properties to that of human, and thus represents a unique model for analysis of EAC tumorigenesis and for comparative studies in human EACs. In a previous study, a set of rat EAC cell lines derived from tumors developed in female crossprogenies between BDII and nonsusceptible rat strains were analyzed by spectral karyotyping (SKY). Here we present an analysis with specific focus on the impact of different genetic backgrounds on the rate and occurrence of genetic aberrations in experimental tumors using data presented in the previous report. We could reveal that the ploidy state, and the abundance and type of structural as well as numerical change differed between the two genetic setups. We have also identified chromosomes harboring aberrations independent of genetic input from the nonsusceptible strains, which provide valuable information for the identification of the genes involved in the development of EAC in the BDII model as well as in human endometrial tumors. (C) 2012 Wiley Periodicals, Inc.

  • 9.
    Falck, Eva
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Hedberg, Carola
    Univ Gothenburg, Inst Biomed, Dept Med & Clin Genet, SE-40530 Gothenburg, Sweden.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Behboudi, Afrouz
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    SKY analysis revealed recurrent numerical and structural chromosome changes in BDII rat endometrial carcinomas2011In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 11, p. 20-Article in journal (Refereed)
    Abstract [en]

    Background: Genomic alterations are common features of cancer cells, and some of these changes are proven to be neoplastic-specific. Such alterations may serve as valuable tools for diagnosis and classification of tumors, prediction of clinical outcome, disease monitoring, and choice of therapy as well as for providing clues to the location of crucial cancer-related genes. Endometrial carcinoma (EC) is the most frequently diagnosed malignancy of the female genital tract, ranking fourth among all invasive tumors affecting women. Cytogenetic studies of human ECs have not produced very conclusive data, since many of these studies are based on karyotyping of limited number of cases and no really specific karyotypic changes have yet been identified. As the majority of the genes are conserved among mammals, the use of inbred animal model systems may serve as a tool for identification of underlying genes and pathways involved in tumorigenesis in humans. In the present work we used spectral karyotyping (SKY) to identify cancer-related aberrations in a well-characterized experimental model for spontaneous endometrial carcinoma in the BDII rat tumor model. Results: Analysis of 21 experimental ECs revealed specific nonrandom numerical and structural chromosomal changes. The most recurrent numerical alterations were gains in rat chromosome 4 (RNO4) and losses in RNO15. The most commonly structural changes were mainly in form of chromosomal translocations and were detected in RNO3, RNO6, RNO10, RNO11, RNO12, and RNO20. Unbalanced chromosomal translocations involving RNO3p was the most commonly observed structural changes in this material followed by RNO11p and RNO10 translocations. Conclusion: The non-random nature of these events, as documented by their high frequencies of incidence, is suggesting for dynamic selection of these changes during experimental EC tumorigenesis and therefore for their potential contribution into development of this malignancy. Comparative molecular analysis of the identified genetic changes in this tumor model with those reported in the human ECs may provide new insights into underlying genetic changes involved in EC development and tumorigenesis.

  • 10.
    Falck, Eva
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Karlsson, Sandra
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Carlsson, Jessica
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Helenius, Gisela
    Örebro University Hospital.
    Karlsson, Mats
    Örebro University Hospital.
    Klinga-Levan, Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Loss of Glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma2010In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 10, p. 46-Article in journal (Refereed)
    Abstract [en]

    Glutathione peroxidase 3 (GPX3) is one of the key enzymes in the cellular defense against oxidative stress and the hepatocyte growth factor receptor, (MET) has been suggested to be influenced by the GPX3 gene expression. In a previous microarray study performed by our group, Gpx3 was identified as a potential biomarker for rat endometrial adenocarcinoma (EAC), since the expression was highly downregulated in rat EAC tumors. Herein, we have investigated the mRNA expression and Gpx3 and Met in rat EAC by real time quantitative PCR (qPCR), and the methylation status of Gpx3. In addition we have examined the expression of GPX3 and MET in 30 human EACs of different FIGO grades and 20 benign endometrial tissues. We found that the expression of GPX3 was uniformly down regulated in both rat and human EAC, regardless of tumor grade or histopathological subtype, implying that the down-regulation is an early event in EAC. The rate of Gpx3 promoter methylation reaches 91%, where biallelic methylation was present in 90% of the methylated tumors. The expression of the Met oncogene was slightly upregulated in EACs that showed loss of expression of Gpx3, but no tumor suppressor activity of Gpx3/GPX3 was detected. Preliminary results also suggest that the production of H2O2 is higher in rat endometrial tumors with down-regulated Gpx3 expression. A likely consequence of loss of GPX3 protein function would be a higher amount of ROS in the cancer cell environment. Thus, the results suggest important clinical implications of the GPX3 expression in EAC, both as a molecular biomarker for EAC and as a potential target for therapeutic interventions.

  • 11.
    Falck, Eva
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Expression patterns of PHF5A/Phf5a and GJa1/Gja1 in rat and human endometrial cancer2013In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 13, no 1, article id 43Article in journal (Refereed)
    Abstract [en]

    Endometrial adenocarcinoma is the most frequently diagnosed cancer of the female genital tract in the western world. Studies of complex diseases can be difficult to perform on human tumor samples due to the high genetic heterogeneity in human. The use of rat models is preferable since rat has similarities in pathogenesis and histopathological properties to that of human.

    A genomic region including the highly conserved Phf5a gene associated to development of EAC has previously been identified in an association study. PHF5A has been suggested to acts as a transcription factor or cofactor in the up regulation of expression of Gja1 gene in the presence of estrogen. It has earlier been shown that the Phf5a gene is down regulated in rat EAC derived cell lines by means of expression microarrays.

    We analyzed the expression of Phf5a and Gja1 by qPCR, and potential relations between the two genes in EAC tumors and non-malignant cell lines derived from the BDII rat model. In addition, the expression pattern of these genes was compared in rat and human EAC tumor samples.

    Changes in expression for Phf5a/PHF5A were found in tumors from both rat and human even though the observed pattern was not completely consistent between the two species. By separating rat EAC cell lines according to the genetic background, a significant lower expression of Phf5a in one of the two cross backgrounds was revealed, but not for the other. In contrast to other studies, Phf5a/PHF5A regulation of Gja1/GJA1 was not revealed in this study.

  • 12.
    Jurcevic, Sanja
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Ejeskär, Katarina
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Verification of microRNA expression in human endometrial adenocarcinoma2016In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 16, no 1, article id 261Article in journal (Refereed)
  • 13.
    Jurcevic, Sanja
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Klinga-Levan, Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    MicroRNA expression in human endometrial adenocarcinoma2014In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 14, no 1, article id 88Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: MicroRNAs are small non-coding RNAs that play crucial roles in the pathogenesis of different cancer types. The aim of this study was to identify miRNAs that are differentially expressed in endometrial adenocarcinoma compared to healthy endometrium. These miRNAs can potentially be used to develop a panel for classification and prognosis in order to better predict the progression of the disease and facilitate the choice of treatment strategy.

    METHODS: Formalin fixed paraffin embedded endometrial tissue samples were collected from the Örebro university hospital. QPCR was used to quantify the expression levels of 742 miRNAs in 30 malignant and 20 normal endometrium samples. After normalization of the qPCR data, miRNAs differing significantly in expression between normal and cancer samples were identified, and hierarchical clustering analysis was used to identify groups of miRNAs with coordinated expression profiles.

    RESULTS: In comparisons between endometrial adenocarcinoma and normal endometrium samples 138 miRNAs were found to be significantly differentially expressed (p < 0.001) among which 112 miRNAs have not been previous reported for endometrial adenocarcinoma.

    CONCLUSION: Our study shows that several miRNAs are differentially expressed in endometrial adenocarcinoma. These identified miRNA hold great potential as target for classification and prognosis of this disease. Further analysis of the differentially expressed miRNA and their target genes will help to derive new biomarkers that can be used for classification and prognosis of endometrial adenocarcinoma.

  • 14.
    Jurcevic, Sanja
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Validation of Suitable Endogenous Control Genes for Quantitative PCR Analysis of microRNA gene expression in a rat model of endometrial cancer2013In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 13, article id 45Article in journal (Refereed)
    Abstract [en]

    Background

    MicroRNAs are small RNA molecules that negatively regulate gene expression by translational inhibition or mRNA cleavage. The discovery that abnormal expression of particular miRNAs contributes to human disease, including cancer, has spurred growing interest in analysing expression profiles of these molecules. Quantitative polymerase chain reaction is frequently used for quantification of miRNA expression due to its sensitivity and specificity. To minimize experimental error in this system an appropriate endogenous control gene must be chosen. An ideal endogenous control gene should be expressed at a constant level across all samples and its expression stability should be unaffected by the experimental procedure.

    Results

    The expression and validation of candidate control genes (4.5S RNA(H) A, Y1, 4.5S RNA(H) B, snoRNA, U87 and U6) was examined in 21 rat cell lines to establish the most suitable endogenous control for miRNA analysis in a rat model of cancer. The stability of these genes was analysed using geNorm and NormFinder algorithms. U87 and snoRNA were identified as the most stable control genes, while Y1 was least stable.

    Conclusion

    This study identified the control gene that is most suitable for normalizing the miRNA expression data in rat. That reference gene will be useful when miRNAs expression are analyzed in order to find new miRNA markers for endometrial cancer in rat.

  • 15.
    Karlsson, Sandra
    et al.
    University of Skövde, School of Life Sciences.
    Holmberg, Erik
    University of Skövde, School of Life Sciences.
    Askerlund, Anders
    University of Skövde, School of Life Sciences.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Altered transforming growth factor-β pathway expression pattern in rat endometrial cancer2007In: Cancer Genetics and Cytogenetics, ISSN 2210-7762, E-ISSN 2210-7770, Vol. 177, no 1, p. 43-50Article in journal (Refereed)
    Abstract [en]

    Endometrial cancer is the most abundant female gynecologic malignancy, ranking fourth in incidence among invasive tumors in women. Females of the BDII inbred rat strain are extremely prone to endometrial adenocarcinoma (EAC), and approximately 90% of virgin females spontaneously develop EAC during their lifetime. Thus, these rats serve as a useful model for the genetic analysis of this malignancy. In the present work, gene expression profiling, by means of cDNA microarrays, was performed on cDNA from endometrial tumor cell lines and from cell lines derived from nonmalignant lesions/normal tissues of the endometrium. We identified several genes associated with the transforming growth factor-β (TGF-β) pathway to be differentially expressed between endometrial tumor cell lines and nonmalignant lesions by using clustering and statistical inference analyses. The expression levels of the genes involved in the TGF-β pathway were independently verified using semiquantitative reverse-transcription polymerase chain reaction. Repressed TGF-β signaling has been reported previously in EAC carcinogenesis, but this is the first report demonstrating aberrations in the expression of TGF-β downstream target genes. We propose that the irregularities present in TGF-β pathway among the majority of the EAC tumor cell lines may affect EAC carcinogenesis.

  • 16.
    Karlsson, Sandra
    et al.
    University of Skövde, School of Life Sciences.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Expression Analysis of Human Endometrial Adenocarcinoma in an Inbred Rat Model2008In: Hormonal Carcinogenesis: Proceedings of the Fifth International Symposium, Springer , 2008, p. 503-509Conference paper (Refereed)
    Abstract [en]

    Endometrial cancer (EC) is the most abundant female gynaecologic malignancy, ranking fourth in incidence among invasive tumors in women. Hormone-related (estrogen-dependent) EC is the prevalent subtype and accounts for approximately 75% of these cancers. Females of the BDII inbred rat strain are extremely prone to endometrial adenocarcinoma, (EAC) and approximately 90% of virgin females spontaneously develop EAC during their life span. Thus, these rats serve as a useful model for the genetic analysis of this malignancy. In the present work, gene expression profiling, by means of cDNA microarrays, was performed on cDNA from endometrial tumor cell lines and from cell lines derived from nonmalignant lesions/normal tissues of the endometrium without specific findings (WSF). We identified numerous genes differentially expressed between endometrial cell lines and WSFs employing clustering analysis and statistical inference analysis. Many of the genes identified are located within or close to the chromosomal regions earlier identified to be associated with EAC susceptibility and development. Several of the genes identified are involved in pathways commonly altered in carcinogenesis, such as the TGF-pathway.

  • 17.
    Karlsson, Sandra
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Klinga-Levan, Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Gene expression profiling predicts a three-gene expression signature of endometrial adenocarcinoma in a rat model2009In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 9, p. Article Number: 12-Article in journal (Refereed)
    Abstract [en]

     

    Background: In the Western world, endometrial cancers are the most common gynaecological neoplastic disorders among women. Initial symptoms are often vague and may be confused with several other conditions or disorders. Thus, there is a need for an easy and reliable diagnostic tool. The objective of this work was to identify a gene expression signature specific for endometrial adenocarcinomas to be used for testing potential endometrial biomarkers.

    Results: Changes in expression between endometrial adenocarcinomas and non-/pre-malignant endometrium from the BDII EAC rat model were compared in cDNA microarray assays. By employing classification analysis (Weka) on the expression data from approximately 5600 cDNA clones and TDT analysis on genotype data, we identified a three-gene signature (Gpx3, Bgn and Tgfb3). An independent analysis of differential expression, revealed a total of 354 cDNA clones with significant changes in expression. Among the 10 best ranked clones, Gpx3, Bgn and Tgfb3 were found.

     

    Conclusion: Taken together, we present a unique data set of genes with different expression patterns between EACs and non-/pre-malignant endometrium, and specifically we found three genes that were confirmed in two independent analyses. These three genes are candidates for an EAC signature and further evaluations of their involvement in EAC tumorigenesis will be undertaken.

  • 18.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Olika och ändå så lika2005In: Perspektiv på högskolan i Skövde, ISSN 1653-8242, Vol. 2, no 3, p. 6-7Article in journal (Other (popular science, discussion, etc.))
  • 19.
    Klinga-Levan, Karin
    et al.
    University of Skövde, School of Life Sciences.
    Levan, Göran
    The BDII inbred rat: A model for genetic analysis of endometrial carcinoma2005In: Hormonal carcinogenesis IV / [ed] Jonathan J. Li, Sara A. Li, Antonio Llombart-Bosch, Springer Science+Business Media B.V., 2005, p. 247-257Chapter in book (Other academic)
    Abstract [en]

    Finns ej

  • 20.
    Nordlander, Carola
    et al.
    Lundberg Laboratory, CMB-Genetics, Göteborg Univ., Box 462, SE-40530 G., Sweden / Department of Pathology, Lundberg Lab. for Cancer Research, Göteborg, Sweden, Sweden.
    Behboudi, Afrouz
    Department of Pathology, Lundberg Lab. for Cancer Research, Göteborg, Sweden.
    Levan, Göran
    Lundberg Laboratory, CMB-Genetics, Göteborg Univ., Box 462, SE-40530 G., Sweden.
    Klinga Levan, Karin
    University of Skövde, School of Life Sciences.
    Allelic imbalance on chromosome 10 in rat endometrial adenocarcinomas2005In: Cancer Genetics and Cytogenetics, ISSN 2210-7762, E-ISSN 2210-7770, Vol. 156, no 2, p. 158-166Article in journal (Refereed)
    Abstract [en]

    Earlier work using comparative genome hybridization (CGH) has shown that rat chromosome 10 (RNO10) is frequently involved in cytogenetic aberrations in BDII rat endometrial adenocarcinomas (EAC). Relative reduction in copy number (chromosomal deletions) was seen in the proximal to middle part of the chromosome, whereas there were increases in copy number in the distal part. The occurrence of RNO10 aberrations was further analyzed in DNA from primary tumor material from 42 EACs and 3 benign endometrial tumors using allelotyping of microsatellite markers. We found frequently that there were 4 quite distinct RNO10 regions that exhibited allelic imbalance. Based on these findings we believe that genes with relevance to EAC tumor development are situated in each of these chromosome regions. Extrapolation of our microsatellite marker data to the rat draft DNA sequence will facilitate the definition of the regions at the level of the DNA and to select and characterize candidate genes within each of the affected chromosome regions.

  • 21.
    Nordlander, Carola
    et al.
    CMB-Genetics, Lundberg Laboratory, Göteborg University, SE 40530 Gothenhurg, Sweden.
    Karlsson, Sandra
    University of Skövde, School of Life Sciences.
    Karlsson, Åsa
    CMB-Genetics, Lundberg Laboratory, Göteborg University, SE 40530 Gothenhurg, Sweden / Division of Medicine/Oncology, Stanford School of Medicine, Stanford, CA 94305, United States.
    Sjöling, Åsa
    Institute of Biomedicine, Department of Microbiology and Immunology, Göteborg University, SE 40530 Gothenburg, Sweden.
    Winnes, Marta
    CMB-Genetics, Lundberg Laboratory, Göteborg University, SE 40530 Gothenhurg, Sweden / Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, 41345 Gothenburg, Sweden.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Behboudi, Afousz
    Institute of Biomedicine, Department of Clinical Genetics, Göteborg University, SE 40530 Gothenburg, Sweden / Institute of Biomedicine, Dept. Clinical Genetics, Göteborg University, 40530 Gothenburg, Sweden.
    Analysis of chromosome 10 aberrations in rat endometrial cancer: evidence for a tumor suppressor locus distal to Tp532007In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 120, no 7, p. 1472-1481Article in journal (Refereed)
    Abstract [en]

    We have recently shown in the BDII rat model of human endometrial adenocarcinoma (EAC), rat chromosome 10 (RNO10) is frequently involved in chromosomal aberrations. In the present study, we investigated the association between RNO10 deletions, allelic imbalance (AI) at RNO10q24 and Tp53 mutation in 27 rat EAC tumors. We detected chromosomal breakage accompanied by loss of proximal and/or gain of distal parts of RNO10 in approximately 2/3 of the tumors. This finding is suggestive of a tumor suppressor activity encoded from the proximal RNO10. Given the fact that Tp53 is located at RNO10q24-q25, we then performed Tp53 mutation analysis. However, we could not find a strong correlation between AI/deletions at RNO10q24 and Tp53 mutation. Instead, the observed patterns for AI, chromosomal breaks and deletions suggest that major selection was directed against a region located close to, but distal of Tp53. In different human malignancies a similar situation of AI at chromosome band 17p13.3 (HSA17p13.3) unassociated with TP53 mutation has been observed. Although RNO10 is largely homologous to HSA17, the conservation with respect to gene order among them is not extensive. We utilized publicly available draft DNA sequences to study intrachromosomal rearrangement during the divergence between HSA17 and RNO10. By using reciprocal comparison of rat and human genome data, we could substantially narrow down the candidate tumor suppressor region in rat from 3 Mb to a chromosomal segment of about 0.5 Mb in size. These results provide scientific groundwork for identification of the putative tumor suppressor gene(s) at 17p13.3 in human tumors

  • 22. Nordlander, Carola
    et al.
    Samuelsson, Emma
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Behboudi, Afrouz
    Recurrent Chromosome 10 Aberrations and Tp53 Mutations in Rat Endometrial Adenocarcinomas2008In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 617, p. 519-525Article in journal (Refereed)
    Abstract [en]

    Human genetic heterogeneity and differences in the environment and life style make analysis of complex diseases such as cancer difficult. By using inbred animal strains, the genetic variability can be minimized and the environmental factors can be reasonably controlled. Endometrial adenocarcinoma (EAC) is the most common gynecologic malignancy, ranking fourth in incidence among tumors in women. The inbred BDII rat strain is genetically prone to spontaneously develop hormone-related EAC, and can be used as a tool to investigate and characterize genetic changes in this tumor type. In the present project, BDII females were crossed to males from two nonsusceptible rat strains and F1, F2, and backcross progeny were produced. Genetic and molecular genetic analysis of tumors showed that rat chromosome 10 (RNO10) was frequently involved in genetic changes. Our data indicate that often there was loss of chromosomal material in the proximal to middle part of the chromosome followed by gains in distal RNO10. This suggested that there is a tumor suppressor gene(s) in the proximal to middle part of RNO10 and an oncogene(s) in the distal part of the chromosome with potential significance in EAC development. The Tp53 gene, located at band RNO10q24-q25, was a strong candidate target for the observed aberrations affecting the middle part of the chromosome. However, our Tp53 gene mutation analyses suggested that a second gene situated very close to Tp53 might be the main target for the observed pattern of genetic changes.

  • 23.
    Olofsson, Peter
    et al.
    Section for Medical Inflammation Research, Lund University, Sweden.
    Johansson, Åsa
    Section for Medical Inflammation Research, Lund University, Sweden.
    Wedekind, Dirk
    Institute for Laboratory Animal Science and Central Animal Laboratory Medical School of Hannover, Hannover, Germany.
    Klöting, Ingrid
    Department of Laboratory Animal Science, Medical Faculty, University of Greifswald, Karlsburg, Germany.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Lu, Shemin
    Section for Medical Inflammation Research, Lund University, Sweden.
    Holmdahl, Rikard
    Section for Medical Inflammation Research, Lund University, Sweden.
    Inconsistent susceptibility to autoimmunity in inbred LEW rats is due to genetic crossbreeding involving segregating of the arthritis-regulation gene Ncf12004In: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 83, no 5, p. 765-771Article in journal (Refereed)
    Abstract [en]

    We recently identified a single-nucleotide polymorphism in the Ncf1 gene, a component of the NADPH oxidase complex, to be the cause of one of the strongest identified loci for arthritis severity in rats. This polymorphism was found to be naturally occurring in a collection of inbred rat strains as well as in wild rats. Among the inbred strains we found that different LEW substrains (LEW/Ztm and LEW/Mol), originating from different breeders, showed an allelic discrepancy in Ncf1, suggesting an impact on arthritis susceptibility between these substrains. In fact, the LEW/Mol strain was completely resistant to pristane-induced arthritis, in contrast to the LEW/Ztm strain, which was susceptible. Moreover, the LEW/Mol strain had higher production of radical oxygen species in peripheral blood leukocytes, a phenomenon most likely regulated by the polymorphisms in the Ncf1 gene. However, the phenotypic difference between LEW/Mol and LEW/Ztm is most likely a combination of several genes, of which Ncf1 is suggested to be the major regulating gene. This has also been confirmed by previous linkage analyses involving the LEW/Ztm strain which shows that a QTL on chromosome 12, most likely caused by polymorphism of Ncf1, is the major regulatory gene but that other loci are contributing. That more genes are likely to contribute was shown by a complete genome comparison of the LEW/Ztm and the LEW/Mol rat strains that uncovered an introduction of approximately 37% non-LEW genome into the LEW/Mol strain, which probably was caused by past crossbreeding. Therefore, the LEW/Mol should be regarded as a recombinant inbred strain.

  • 24.
    Petersen, Greta
    et al.
    Dept. of Cell/Molec. Biol.-Genetics, Göteborg University, Box 462, SE 40530 Göteborg, Sweden.
    Johnson, Per
    Dept. of Cell/Molec. Biol.-Genetics, Göteborg University, Box 462, SE 40530 Göteborg, Sweden.
    Andersson, Lars
    Dept. of Cell/Molec. Biol.-Genetics, Göteborg University, Box 462, SE 40530 Göteborg, Sweden.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Gómez-Fabre, Pedro M.
    University of Skövde, School of Life Sciences.
    Ståhl, Fredrik
    Dept. of Cell/Molec. Biol.-Genetics, Göteborg University, Box 462, SE 40530 Göteborg, Sweden / School of Health Sciences, University College of Borås, Borås, Sweden.
    RatMap - rat genome tools and data2005In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 33, no DATABASE ISS., p. D492-D494Article in journal (Refereed)
    Abstract [en]

    The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB–Genetics at Göteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided.

  • 25.
    Roshani, L.
    et al.
    CMB-Genetics, Lundberg Laboratory, Göteborg University, Göteborg, Sweden.
    Mallon, P.
    Department of Animal Science, Medical School of Hannover, Hannover 30625, Germany.
    Sjöstrand, E.
    CMB-Genetics, Lundberg Laboratory, Göteborg University, Göteborg, Sweden.
    Wedekind, D.
    Department of Animal Science, Medical School of Hannover, Hannover 30625, Germany.
    Szpirer, J.
    Université Libre de Bruxelles, IBMM, Gosselies, Belgium.
    Szpirer, C.
    Université Libre de Bruxelles, IBMM, Gosselies, Belgium.
    Hedrich, H. J.
    University of Skövde, School of Life Sciences.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences.
    Genetic analysis of susceptibility to endometrial adenocarcinoma in the BDII rat model2005In: Cancer Genetics and Cytogenetics, ISSN 2210-7762, E-ISSN 2210-7770, Vol. 158, no 2, p. 137-141Article in journal (Refereed)
    Abstract [en]

    Most cancers are genetically complex and heterogeneous, a serious obstacle to identifying specific genes underlying the disease. If inbred animal models are used, then both the genetic constitution and environmental influences can be carefully controlled. Females of the BDII inbred rat strain are genetically predisposed to endometrial cancer; more than 90% of virgin BDII females will develop endometrial adenocarcinoma (EAC) during their life span. BDII females were crossed to males from inbred strains with low EAC incidence (SPRD or BN). When F1 males were backcrossed to BDII females to generate N1 populations of offspring, about one fourth of the female progeny developed EAC. With transmission disequilibrium test analysis, significant association was detected in three chromosomal regions (on RNO1, RNO11, and RNO17) in the SPRD crosses and in the short arm of RNO20 in the BN crosses. It appears that several susceptibility genes with minor but cooperating effects are responsible for the susceptibility. Furthermore, it seems clear from the interstrain crosses not only that the onset of tumors depends on the presence of susceptibility alleles from the EAC-prone BDII strain, but also that tumor development is affected by the contribution of a genetic component derived from the nonsusceptible strains.

  • 26.
    Ulfenborg, Benjamin
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jurcevic, Sanja
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Lindelöf, Angelica
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    miREC: a database of miRNAs involved in the development of endometrial cancer2015In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 8, no 1, article id 104Article in journal (Refereed)
    Abstract [en]

    Background

    Endometrial cancer (EC) is the most frequently diagnosed gynecological malignancy and the fourth most common cancer diagnosis overall among women. As with many other forms of cancer, it has been shown that certain miRNAs are differentially expressed in EC and these miRNAs are believed to play important roles as regulators of processes involved in the development of the disease. With the rapidly growing number of studies of miRNA expression in EC, there is a need to organize the data, combine the findings from experimental studies of EC with information from various miRNA databases, and make the integrated information easily accessible for the EC research community.

    Findings

    The miREC database is an organized collection of data and information about miRNAs shown to be differentially expressed in EC. The database can be used to map connections between miRNAs and their target genes in order to identify specific miRNAs that are potentially important for the development of EC. The aim of the miREC database is to integrate all available information about miRNAs and target genes involved in the development of endometrial cancer, and to provide a comprehensive, up-to-date, and easily accessible source of knowledge regarding the role of miRNAs in the development of EC. Database URL: http://www.mirecdb.orgwebcite.

    Conclusions

    Several databases have been published that store information about all miRNA targets that have been predicted or experimentally verified to date. It would be a time-consuming task to navigate between these different data sources and literature to gather information about a specific disease, such as endometrial cancer. The miREC database is a specialized data repository that, in addition to miRNA target information, keeps track of the differential expression of genes and miRNAs potentially involved in endometrial cancer development. By providing flexible search functions it becomes easy to search for EC-associated genes and miRNAs from different starting points, such as differential expression and genomic loci (based on genomic aberrations).

  • 27.
    Ulfenborg, Benjamin
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Classification of tumor samples from expression data using decision trunks2013In: Cancer Informatics, ISSN 1176-9351, E-ISSN 1176-9351, Vol. 12, p. 53-66Article in journal (Refereed)
    Abstract [en]

    We present a novel machine learning approach for the classification of cancer samples using expression data. We refer to the method as "decision trunks," since it is loosely based on decision trees, but contains several modifications designed to achieve an algorithm that: (1) produces smaller and more easily interpretable classifiers than decision trees; (2) is more robust in varying application scenarios; and (3) achieves higher classification accuracy. The decision trunk algorithm has been implemented and tested on 26 classification tasks, covering a wide range of cancer forms, experimental methods, and classification scenarios. This comprehensive evaluation indicates that the proposed algorithm performs at least as well as the current state of the art algorithms in terms of accuracy, while producing classifiers that include on average only 2-3 markers. We suggest that the resulting decision trunks have clear advantages over other classifiers due to their transparency, interpretability, and their correspondence with human decision-making and clinical testing practices. © the author(s), publisher and licensee Libertas Academica Ltd.

  • 28.
    Ulfenborg, Benjamin
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Genome-wide discovery of miRNAs using ensembles of machine learning algorithms and logistic regression2015In: International Journal of Data Mining and Bioinformatics, ISSN 1748-5681, Vol. 13, no 4, p. 338-359Article in journal (Refereed)
    Abstract [en]

    In silico prediction of novel miRNAs from genomic sequences remains a challenging problem. This study presents a genome-wide miRNA discovery software package called GenoScan and evaluates two hairpin classification methods. These methods, one ensemble-based and one using logistic regression were benchmarked along with 15 published methods. In addition, the sequence-folding step is addressed by investigating the impact of secondary structure prediction methods and the choice of input sequence length on prediction performance. Both the accuracy of secondary structure predictions and the miRNA prediction are evaluated. In the benchmark of hairpin classification methods, the regression model achieved highest classification accuracy. Of the structure prediction methods evaluated, ContextFold achieved the highest agreement between predicted and experimentally determined structures. However, both the choice of secondary structure prediction method and input sequence length had limited impact on hairpin classification performance.

  • 29.
    Ulfenborg, Benjamin
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    GenoScan: Genomic Scanner for Putative miRNA Precursors2014In: Bioinformatics Research and Applications: 10th International Symposium, ISBRA 2014, Zhangjiajie, China, June 28-30, 2014. Proceedings / [ed] Mitra Basu, Yi Pan, Jianxin Wang, Springer, 2014, p. 266-277Conference paper (Refereed)
    Abstract [en]

    The significance of miRNAs has been clarified over the last decade as thousands of these small non-coding RNAs have been found in a wide variety of species. By binding to specific target mRNAs, miRNAs act as negative regulators of gene expression in many different biological processes. Computational approaches for discovery of miRNAs in genomes usually take the form of an algorithm that scans sequences for miRNA-characteristic hairpins, followed by classification of those hairpins as miRNAs or nonmiRNAs. In this study, two new approaches to genome-scale miRNA discovery are presented and evaluated. These methods, one ensemble-based and one using logistic regression, have been designed to detect miRNA candidates without relying on conservation or transcriptome data, and to achieve high-confidence predictions in reasonable computational time. GenoScan achieves high accuracy with a good balance between sensitivity and specificity. In a benchmark evaluation including 15 previously published methods, the regression-based approach in GenoScan achieved the highest classification accuracy.

1 - 29 of 29
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf