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Lubovac-Pilav, ZelminaORCID iD iconorcid.org/0000-0001-6427-0315
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Publications (10 of 20) Show all publications
Weishaupt, H., Johansson, P., Sundström, A., Lubovac-Pilav, Z., Olsson, B., Nelander, S. & Swartling, F. J. (2019). Batch-normalization of cerebellar and medulloblastoma gene expression datasets utilizing empirically defined negative control genes. Bioinformatics, 35(18), 3357-3364
Open this publication in new window or tab >>Batch-normalization of cerebellar and medulloblastoma gene expression datasets utilizing empirically defined negative control genes
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2019 (English)In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 35, no 18, p. 3357-3364Article in journal (Refereed) Published
Abstract [en]

Motivation: Medulloblastoma (MB) is a brain cancer predominantly arising in children. Roughly 70% of patients are cured today, but survivors often suffer from severe sequelae. MB has been extensively studied by molecular profiling, but often in small and scattered cohorts. To improve cure rates and reduce treatment side effects, accurate integration of such data to increase analytical power will be important, if not essential.

Results: We have integrated 23 transcription datasets, spanning 1350 MB and 291 normal brain samples. To remove batch effects, we combined the Removal of Unwanted Variation (RUV) method with a novel pipeline for determining empirical negative control genes and a panel of metrics to evaluate normalization performance. The documented approach enabled the removal of a majority of batch effects, producing a large-scale, integrative dataset of MB and cerebellar expression data. The proposed strategy will be broadly applicable for accurate integration of data and incorporation of normal reference samples for studies of various diseases. We hope that the integrated dataset will improve current research in the field of MB by allowing more large-scale gene expression analyses.

Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Bioinformatics and Systems Biology
Research subject
Bioinformatics
Identifiers
urn:nbn:se:his:diva-16769 (URN)10.1093/bioinformatics/btz066 (DOI)000487327500019 ()30715209 (PubMedID)2-s2.0-85072349088 (Scopus ID)
Available from: 2019-04-11 Created: 2019-04-11 Last updated: 2019-10-11Bibliographically approved
Borgmästars, E., de Weerd, H. A., Lubovac-Pilav, Z. & Sund, M. (2019). miRFA: an automated pipeline for microRNA functional analysis with correlation support from TCGA and TCPA expression data in pancreatic cancer. BMC Bioinformatics, 20(1), 1-17, Article ID 393.
Open this publication in new window or tab >>miRFA: an automated pipeline for microRNA functional analysis with correlation support from TCGA and TCPA expression data in pancreatic cancer
2019 (English)In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 20, no 1, p. 1-17, article id 393Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: MicroRNAs (miRNAs) are small RNAs that regulate gene expression at a post-transcriptional level and are emerging as potentially important biomarkers for various disease states, including pancreatic cancer. In silico-based functional analysis of miRNAs usually consists of miRNA target prediction and functional enrichment analysis of miRNA targets. Since miRNA target prediction methods generate a large number of false positive target genes, further validation to narrow down interesting candidate miRNA targets is needed. One commonly used method correlates miRNA and mRNA expression to assess the regulatory effect of a particular miRNA. The aim of this study was to build a bioinformatics pipeline in R for miRNA functional analysis including correlation analyses between miRNA expression levels and its targets on mRNA and protein expression levels available from the cancer genome atlas (TCGA) and the cancer proteome atlas (TCPA). TCGA-derived expression data of specific mature miRNA isoforms from pancreatic cancer tissue was used.

RESULTS: Fifteen circulating miRNAs with significantly altered expression levels detected in pancreatic cancer patients were queried separately in the pipeline. The pipeline generated predicted miRNA target genes, enriched gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways. Predicted miRNA targets were evaluated by correlation analyses between each miRNA and its predicted targets. MiRNA functional analysis in combination with Kaplan-Meier survival analysis suggest that hsa-miR-885-5p could act as a tumor suppressor and should be validated as a potential prognostic biomarker in pancreatic cancer.

CONCLUSIONS: Our miRNA functional analysis (miRFA) pipeline can serve as a valuable tool in biomarker discovery involving mature miRNAs associated with pancreatic cancer and could be developed to cover additional cancer types. Results for all mature miRNAs in TCGA pancreatic adenocarcinoma dataset can be studied and downloaded through a shiny web application at https://emmbor.shinyapps.io/mirfa/ .

Place, publisher, year, edition, pages
BioMed Central, 2019
Keywords
Functional enrichment, Mature miRNA, Pancreatic cancer, TCGA, TCPA, miRNA functional analysis, miRNA target prediction
National Category
Bioinformatics and Systems Biology
Research subject
Bioinformatics; INF502 Biomarkers
Identifiers
urn:nbn:se:his:diva-17456 (URN)10.1186/s12859-019-2974-3 (DOI)000475761100001 ()31311505 (PubMedID)2-s2.0-85069159500 (Scopus ID)
Available from: 2019-07-19 Created: 2019-07-19 Last updated: 2019-11-08Bibliographically approved
Tilevik, D., Saxenborn, P., Tilevik, A., Fagerlind, M., Lubovac-Pilav, Z., Pernestig, A.-K. & Enroth, H. (2019). Using next-generation sequencing to study biodiversity in Klebsiella spp. isolated from patients with suspected sepsis. In: : . Paper presented at 29th European Congress of Clinical Microbiology and Infectious Diseases, ECCMID, Amsterdam, Netherlands, 13-16 April, 2019.
Open this publication in new window or tab >>Using next-generation sequencing to study biodiversity in Klebsiella spp. isolated from patients with suspected sepsis
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2019 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Medical and Health Sciences Infectious Medicine Microbiology
Research subject
Infection Biology; Bioinformatics
Identifiers
urn:nbn:se:his:diva-18200 (URN)
Conference
29th European Congress of Clinical Microbiology and Infectious Diseases, ECCMID, Amsterdam, Netherlands, 13-16 April, 2019
Available from: 2020-02-07 Created: 2020-02-07 Last updated: 2020-03-12Bibliographically approved
Riquelme Medina, I. & Lubovac-Pilav, Z. (2016). Gene Co-Expression Network Analysis for Identifying Modules and Functionally Enriched Pathways in Type 1 Diabetes. PLoS ONE, 11(6), Article ID e0156006.
Open this publication in new window or tab >>Gene Co-Expression Network Analysis for Identifying Modules and Functionally Enriched Pathways in Type 1 Diabetes
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 6, article id e0156006Article in journal (Refereed) Published
Abstract [en]

Type 1 diabetes (T1D) is a complex disease, caused by the autoimmune destruction of the insulin producing pancreatic beta cells, resulting in the body?s inability to produce insulin. While great efforts have been put into understanding the genetic and environmental factors that contribute to the etiology of the disease, the exact molecular mechanisms are still largely unknown. T1D is a heterogeneous disease, and previous research in this field is mainly focused on the analysis of single genes, or using traditional gene expression profiling, which generally does not reveal the functional context of a gene associated with a complex disorder. However, network-based analysis does take into account the interactions between the diabetes specific genes or proteins and contributes to new knowledge about disease modules, which in turn can be used for identification of potential new biomarkers for T1D. In this study, we analyzed public microarray data of T1D patients and healthy controls by applying a systems biology approach that combines network-based Weighted Gene Co-Expression Network Analysis (WGCNA) with functional enrichment analysis. Novel co-expression gene network modules associated with T1D were elucidated, which in turn provided a basis for the identification of potential pathways and biomarker genes that may be involved in development of T1D.

Place, publisher, year, edition, pages
Public Library of Science, 2016
National Category
Bioinformatics and Systems Biology
Research subject
Bioinformatics
Identifiers
urn:nbn:se:his:diva-12398 (URN)10.1371/journal.pone.0156006 (DOI)000377369700028 ()27257970 (PubMedID)2-s2.0-84973455067 (Scopus ID)
Available from: 2016-06-10 Created: 2016-06-10 Last updated: 2019-11-18
Lubovac-Pilav, Z., Borràs, D. M., Ponce, E. & Louie, M. C. (2013). Using expression profiling to understand the effects of chronic cadmium exposure on mcf-7 breast cancer cells. PLoS ONE, 8(12), Article ID e84646.
Open this publication in new window or tab >>Using expression profiling to understand the effects of chronic cadmium exposure on mcf-7 breast cancer cells
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e84646Article in journal (Refereed) Published
Abstract [en]

Cadmium is a metalloestrogen known to activate the estrogen receptor and promote breast cancer cell growth. Previous studies have implicated cadmium in the development of more malignant tumors; however the molecular mechanisms behind this cadmium-induced malignancy remain elusive. Using clonal cell lines derived from exposing breast cancer cells to cadmium for over 6 months (MCF-7-Cd4, -Cd6, -Cd7, -Cd8 and -Cd12), this study aims to identify gene expression signatures associated with chronic cadmium exposure. Our results demonstrate that prolonged cadmium exposure does not merely result in the deregulation of genes but actually leads to a distinctive expression profile. The genes deregulated in cadmium-exposed cells are involved in multiple biological processes (i.e. cell growth, apoptosis, etc.) and molecular functions (i.e. cadmium/metal ion binding, transcription factor activity, etc.). Hierarchical clustering demonstrates that the five clonal cadmium cell lines share a common gene expression signature of breast cancer associated genes, clearly differentiating control cells from cadmium exposed cells. The results presented in this study offer insights into the cellular and molecular impacts of cadmium on breast cancer and emphasize the importance of studying chronic cadmium exposure as one possible mechanism of promoting breast cancer progression.

Place, publisher, year, edition, pages
Public Library of Science, 2013
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-8714 (URN)10.1371/journal.pone.0084646 (DOI)000328745100180 ()24376830 (PubMedID)2-s2.0-84893179608 (Scopus ID)
Available from: 2014-01-02 Created: 2014-01-02 Last updated: 2019-11-18Bibliographically approved
Lubovac-Pilav, Z. (2012). Integrative Approach for Detection of Functional Modules from Protein-Protein Interaction Networks. In: Weibo Cai & Hao Hong (Ed.), Protein-Protein Interactions: Computational and Experimental Tools (pp. 97-112). INTECH
Open this publication in new window or tab >>Integrative Approach for Detection of Functional Modules from Protein-Protein Interaction Networks
2012 (English)In: Protein-Protein Interactions: Computational and Experimental Tools / [ed] Weibo Cai & Hao Hong, INTECH, 2012, p. 97-112Chapter in book (Refereed)
Place, publisher, year, edition, pages
INTECH, 2012
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-5919 (URN)10.5772/37858 (DOI)978-953-51-0397-4 (ISBN)
Available from: 2012-06-04 Created: 2012-06-04 Last updated: 2017-11-27Bibliographically approved
Tina, E., Malakkaran Lindqvist, B., Gabrielson, M., Lubovac, Z., Wegman, P. & Wingren, S. (2012). The mitochondrial transporter SLC25A43 is frequently deleted and may influence cell proliferation in HER2-positive breast tumors. BMC Cancer, 12, Article number 350
Open this publication in new window or tab >>The mitochondrial transporter SLC25A43 is frequently deleted and may influence cell proliferation in HER2-positive breast tumors
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2012 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, p. Article number 350-Article in journal (Refereed) Published
Abstract [en]

Background: Overexpression of the human epidermal growth factor receptor (HER) 2 is associated with poor prognosis and shortened survival in breast cancer patients. HER2 is a potent activator of several signaling pathways that support cell survival, proliferation and metabolism. In HER2- positive breast cancer there are most likely unexplored proteins that act directly or indirectly downstream of well established pathways and take part in tumor development and treatment response.

Methods: In order to identify novel copy number variations (CNVs) in HER2-positive breast cancer whole-genome single nucleotide polymorphism (SNP) arrays were used. A PCR-based loss of heterozygosis (LOH) assay was conducted to verify presence of deletion in HER2-positive breast cancer cases but also in HER2 negative breast cancers, cervical cancers and lung cancers. Screening for mutations was performed using single-strand conformation polymorphism (SSCP) followed by PCR sequencing. Protein expression was evaluated with immunohistochemistry (IHC).

Results: A common deletion at chromosome Xq24 was found in 80% of the cases. This locus harbors the gene solute carrier (SLC) family 25A member 43 (SLC25A43) encoding for a mitochondrial transport protein. The LOH assay revealed presence of SLC25A43 deletion in HER2-positive (48%), HER2-negative (9%), cervical (42%) and lung (67%) cancers. HER2- positive tumors with negative or low SLC25A43 protein expression had significantly lower S-phase fraction compared to tumors with medium or high expression (P = 0.024).

Conclusions: We have found deletion in the SLC25A43 gene to be a common event in HER2-positive breast cancer as well as in other cancers. In addition, the SLC25A43 protein expression was shown to be related to S-phase fraction in HER2-positive breast cancer. Our results indicate a possible role of SLC25A43 in HER2-positive breast cancer and support the hypothesis of altered mitochondrial function in cancer.

Place, publisher, year, edition, pages
BioMed Central, 2012
Keywords
Breast cancer, HER2, SLC25A43, S-phase
National Category
Biological Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-6540 (URN)10.1186/1471-2407-12-350 (DOI)000309407100001 ()22883974 (PubMedID)2-s2.0-84864803696 (Scopus ID)
Available from: 2012-10-16 Created: 2012-10-16 Last updated: 2017-12-07Bibliographically approved
Carlsson, J., Davidsson, S., Helenius, G., Karlsson, M., Lubovac, Z., Andren, O., . . . Klinga-Levan, K. (2011). A miRNA expression signature that separates between normal and malignant prostate tissues. Cancer Cell International, 11, 14
Open this publication in new window or tab >>A miRNA expression signature that separates between normal and malignant prostate tissues
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2011 (English)In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 11, p. 14-Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BioMed Central, 2011
National Category
Cancer and Oncology
Research subject
Medical sciences
Identifiers
urn:nbn:se:his:diva-5544 (URN)10.1186/1475-2867-11-14 (DOI)000292110200001 ()2-s2.0-79957484812 (Scopus ID)
Available from: 2012-03-09 Created: 2012-03-01 Last updated: 2017-12-07Bibliographically approved
Carlsson, J., Helenius, G., Karlsson, M., Lubovac, Z., Andrén, O., Olsson, B. & Klinga-Levan, K. (2010). Validation of suitable endogenous control genes for expression studies of miRNA in prostate cancer tissues. Cancer Genetics and Cytogenetics, 202(2), 71-75
Open this publication in new window or tab >>Validation of suitable endogenous control genes for expression studies of miRNA in prostate cancer tissues
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2010 (English)In: Cancer Genetics and Cytogenetics, ISSN 2210-7762, E-ISSN 2210-7770, Vol. 202, no 2, p. 71-75Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier Inc., 2010
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-4712 (URN)10.1016/j.cancergencyto.2010.02.009 (DOI)000282862400001 ()20875868 (PubMedID)2-s2.0-77957037880 (Scopus ID)
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Available from: 2011-02-02 Created: 2011-02-02 Last updated: 2017-12-11Bibliographically approved
Lubovac, Z. (2009). Investigating Topological and Functional Features of Multimodular Proteins. Journal of Biomedicine and Biotechnology, Article Number: 472415
Open this publication in new window or tab >>Investigating Topological and Functional Features of Multimodular Proteins
2009 (English)In: Journal of Biomedicine and Biotechnology, ISSN 1110-7243, E-ISSN 1110-7251, p. Article Number: 472415-Article in journal (Refereed) Published
Abstract [en]

To generate functional modules as functionally and structurally cohesive formations in protein interaction networks (PINs) constitutes an important step towards understanding how modules communicate on a higher level of the PIN organisation that underlies cell functionality. However, we need to understand how individual modules communicate and are organized into the higher-order structure(s) of the PIN organization that underlies cell functionality. In an attempt to contribute to this understanding, we make an assumption that the proteins reappearing in several modules, termed here as multimodular proteins (MMPs), may be useful in building higher-order structure(s) as they may constitute communication points between different modules. In this paper, we investigate common properties shared by these proteins and compare them with the properties of so called single-modular proteins (SMPs) by analyzing three aspects: functional aspect, that is, annotation of the proteins, topological aspect that is betweenness centrality of the proteins, and lethality. Furthermore, we investigate the interconnectivity role of some proteins that are identified as functionally and topologically important.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2009
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-4311 (URN)10.1155/2009/472415 (DOI)000274887700001 ()20069113 (PubMedID)2-s2.0-75149193122 (Scopus ID)
Available from: 2010-08-24 Created: 2010-08-24 Last updated: 2017-12-12Bibliographically approved
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