Björn Olsson | University of Skövde (original) (raw)

Papers by Björn Olsson

Cancer Genetics and Cytogenetics, 2007

Breast cancer is the most common malignancy among women and accounts for over one million new cas... more Breast cancer is the most common malignancy among women and accounts for over one million new cases worldwide per year. Lymph node-negative breast cancer patients are reputed as having a better prognosis than lymph node-positive ones. Around 20% of the lymph node-negative patients die within 10 years after diagnosis. To improve the prognostics of node-negative breast cancer, it is important to understand the underlying biologic mechanisms promoting survival, such as specific genetic changes in the tumor genome. In this study, CGH was applied to analyze 64 tumors from node-negative breast cancer patients to identify DNA copy number changes in chromosomes and chromosome regions that may be correlated to survival. The main findings show gains at 4q, 5q31 approximately qter, 6q12 approximately q16, and 12q14 approximately q22, as well as losses of 17p, 18p, and Xq, which were significantly more recurrent in tumors from deceased patients than in tumors from survivors. The average number of chromosomal changes was higher in the tumors from deceased compared to the survivor tumors. Our findings suggest that tumors with specific chromosomal aberrations at 4q, 5q31 approximately qter, 6q12 approximately q16, 12q14 approximately q22, 17p, 18p, and Xq result in an aggressive form of breast cancer and that these patients are predisposed to succumb to breast cancer.

BMC Cancer, 2008

Background: It is of great significance to find better markers to correctly distinguish between h... more Background: It is of great significance to find better markers to correctly distinguish between high-risk and low-risk breast cancer patients since the majority of breast cancer cases are at present being overtreated. Methods: 46 tumours from node-negative breast cancer patients were studied with gene expression microarrays. A t-test was carried out in order to find a set of genes where the expression might predict clinical outcome. Two classifiers were used for evaluation of the gene lists, a correlation-based classifier and a Voting Features Interval (VFI) classifier. We then evaluated the predictive accuracy of this expression signature on tumour sets from two similar studies on lymph-node negative patients. They had both developed gene expression signatures superior to current methods in classifying node-negative breast tumours. These two signatures were also tested on our material. Results: A list of 51 genes whose expression profiles could predict clinical outcome with high accuracy in our material (96% or 89% accuracy in cross-validation, depending on type of classifier) was developed. When tested on two independent data sets, the expression signature based on the 51 identified genes had good predictive qualities in one of the data sets (74% accuracy), whereas their predictive value on the other data set were poor, presumably due to the fact that only 23 of the 51 genes were found in that material. We also found that previously developed expression signatures could predict clinical outcome well to moderately well in our material (72% and 61%, respectively). Conclusion: The list of 51 genes derived in this study might have potential for clinical utility as a prognostic gene set, and may include candidate genes of potential relevance for clinical outcome in breast cancer. According to the predictions by this expression signature, 30 of the 46 patients may have benefited from different adjuvant treatment than they recieved. Trial registration: The research on these tumours was approved by the Medical Faculty Research Ethics Committee (Medicinska fakultetens forskningsetikkommitté, Göteborg, Sweden (S164-02)).

BMC cancer, Jan 2, 2016

MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and progression... more MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and progression. In a previous study we identified 138 miRNAs as differentially expressed in endometrial adenocarcinoma compared to normal tissues. One of these miRNAs was miRNA-34a, which regulates several genes involved in the Notch pathway, which is frequently altered in endometrial cancer. The aims of this study were to verify the differential expression of a subset of miRNAs and to scrutinize the regulatory role of mir-34a on the target genes NOTCH1 and DLL1. Twenty-five miRNAs that were previously identified as differentially expressed were subjected to further analysis using qPCR. To investigate the regulation of NOTCH1 and DLL1 by mir-34a, we designed gain- and loss-of-function experiments in Ishikawa and HEK293 cell lines by transfection with a synthetic mir-34a mimic and a mir-34a inhibitor. Of the 25 validated miRNAs, seven were down-regulated and 18 were up-regulated compared to normal endo...

Previous work on host-parasite genetic algorithms consists of specific algorithms, applied to sin... more Previous work on host-parasite genetic algorithms consists of specific algorithms, applied to single example problems. We attempt to design a simple host-parasite genetic algorithm (SHPGA), with the aim of obtaining an algorithm with broad applicability to a wide range of problems. We argue that the benefits of the simplicity of SHPGA are twofold: i) it allows empirical analysis of the performance of the algorithm and comparison with the performance of a corresponding noncoevolutionary GA; and, ii) if performance benefits are found, we can fairly safely attribute them specifically to the use of host-parasite coevolution.

Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent losses distal ... more Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent losses distal to TP53. Myo1c can tightly and specifically bind to PIP2, the substrate of Phos-phoinositide 3-kinase (PI3K), and to Rictor, suggesting a role for MYO1C in the PI3K pathway. This study was designed to examine MYO1C expression status in a panel of well-stratified endometrial carcinomas as well as to assess the biological significance of MYO1C as a tumor suppressor in vitro. We found a significant correlation between the tumor stage and lowered expression of MYO1C in endometrial carcinoma samples. In cell transfection experiments, we found a negative correlation between MYO1C expression and cell proliferation, and MYO1C silencing resulted in diminished cell migration and adhesion. Cells expressing excess of MYO1C had low basal level of phosphorylated protein kinase B (PKB, a.k.a. AKT) and cells with knocked down MYO1C expression showed a quicker phosphorylated AKT (pAKT) response in reaction to serum stimulation. Taken together the present study gives further evidence for tumor suppressor activity of MYO1C and suggests MYO1C mediates its tumor suppressor function through inhibition of PI3K pathway and its involvement in loss of contact inhibition.

Background: In humans, muscle-specific nicotinergic acetylcholine receptor (AChR) is a transmembr... more Background: In humans, muscle-specific nicotinergic acetylcholine receptor (AChR) is a transmembrane protein with five different subunits, coded by CHRNA1, CHRNB, CHRND and CHRNG/CHRNE. The gamma subunit of AChR encoded by CHRNG is expressed during early foetal development, whereas in the adult, the γ subunit is replaced by a ε subunit. Mutations in the CHRNG encoding the embryonal acetylcholine receptor may cause the non-lethal Escobar variant (EVMPS) and lethal form (LMPS) of multiple pterygium syndrome. The MPS is a condition characterised by prenatal growth failure with pterygium and akinesia leading to muscle weakness and severe congenital contractures, as well as scoliosis. Results: Our whole exome sequencing studies have identified one novel and two previously reported homozygous mutations in CHRNG in three families affected by non-lethal EVMPS. The mutations consist of deletion of two nucleotides, cause a frameshift predicted to result in premature termination of the foetally expressed gamma subunit of the AChR.

Previously, we reported a chromium-resistant bacterium, Enterobacter cloacae B2-DHA, isolated fro... more Previously, we reported a chromium-resistant bacterium, Enterobacter cloacae B2-DHA, isolated from the landfills of tannery industries in Bangladesh. Here, we investigated its genetic composition using massively parallel sequencing and comparative analysis with other known Enterobacter genomes. Assembly of the sequencing reads revealed a genome of ~4.21 Mb in size.

Background: MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and... more Background: MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and progression. In a previous study we identified 138 miRNAs as differentially expressed in endometrial adenocarcinoma compared to normal tissues. One of these miRNAs was miRNA-34a, which regulates several genes involved in the Notch pathway, which is frequently altered in endometrial cancer. The aims of this study were to verify the differential expression of a subset of miRNAs and to scrutinize the regulatory role of mir-34a on the target genes NOTCH1 and DLL1.

Here, we report the genomic sequence and genetic composition of an arsenic-resistant bacterium, L... more Here, we report the genomic sequence and genetic composition of an arsenic-resistant bacterium, Lysinibacillus sphaericus B1-CDA. Assembly of the sequencing reads revealed that the genome size is ~4.5 Mb, encompassing ~80% of the chromosomal DNA.

Human pluripotent stem cells-(hPSCs-) derived hepatocytes have the potential to replace many hepa... more Human pluripotent stem cells-(hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models.

This study is a part of our long term project on bioremediation of toxic metals and other polluta... more This study is a part of our long term project on bioremediation of toxic metals and other pollutants for protection of human health and the environment from severe contamination. The information and results presented in this data article are based on both in vitro and in silico experiments. In vitro experiments were used to investigate the presence of arsenic responsive

contributed equally to this work. We report the 5,728,255-bp draft genome sequence of Rhodococcus... more contributed equally to this work. We report the 5,728,255-bp draft genome sequence of Rhodococcus ruber P25, isolated from a soil polluted with halogenated aromatic compounds in the city of Perm, Russia. The strain degrades polychlorinated biphenyls and a broad range of aromatic compounds. It possesses genes that mediate the degradation of biphenyls/polychlorinated biphenyls, naphthalene, and mono-aromatic compounds.

Chromium and chromium containing compounds are discharged into the nature as waste from anthropog... more Chromium and chromium containing compounds are discharged into the nature as waste from anthropogenic activities, such as industries, agriculture, forest farming, mining and metallurgy. Continued disposal of these compounds to the environment leads to development of various lethal diseases in both humans and animals. In this paper, we report a soil borne bacterium, B2-DHA that can be used as a vehicle to effectively remove chromium from the contaminated sources. B2-DHA is resistant to chromium with a MIC value of 1000 mg mL ¡1 potassium chromate. The bacterium has been identified as a Gram negative, Enterobacter cloacae based on biochemical characteristics and 16S rRNA gene analysis. TOF-SIMS and ICP-MS analyses confirmed intracellular accumulation of chromium and thus its removal from the contaminated liquid medium. Chromium accumulation in cells was 320 mg/g of cells dry biomass after 120-h exposure, and thus it reduced the chromium concentration in the liquid medium by as much as 81%. Environmental scanning electron micrograph revealed the effect of metals on cellular morphology of the isolates. Altogether, our results indicate that B2-DHA has the potential to reduce chromium significantly to safe levels from the contaminated environments and suggest the potential use of this bacterium in reducing human exposure to chromium, hence avoiding poisoning.

In silico prediction of novel miRNAs from genomic sequences remains a challenging problem. This s... more 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.

Lecture Notes in Computer Science, 2014

The significance of miRNAs has been clarified over the last decade as thousands of these small no... more 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 non-miRNAs. 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.

Cancer Informatics, 2013

We present a novel machine learning approach for the classification of cancer samples using expre... more 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.

Bull spermatozoa are rich in active miRNAs, and it has been shown that specific spermborne miRNAs... more Bull spermatozoa are rich in active miRNAs, and it has been
shown that specific spermborne miRNAs can be linked to
fertility. Thus, expression profiling of spermatozoa could be
helpful for understanding male fertility and the ability of
spermatozoa to initiate and sustain zygotic, embryonic and
foetal development. Herein we hypothesized that bulls with
moderate to high fertility can be identified by differences in
amounts of certain miRNAs between their ejaculates. RNA
samples from spermatozoa of eight brother pairs (one bull with
high and one with moderate NRR in each pair) of the Holstein
breed were prepared. miRNA was isolated, and the expression
of 178 miRNAs was determined by RT-qPCR. Important
findings were that highly expressed miRNAs, not linked toNRR
status, were identified in the bull sperm samples, which indicate
that these miRNAs have an important role in early embryogenesis. A large fraction of the targets genes were phosphoproteins and genes involved in the regulation of transcription. Seven miRNAs (mir-502-5p, mir-1249, mir-320a, mir-34c-3p, mir-19b-3p, mir-27a-5p and mir-148b-3p) were differentially expressed between bulls with moderate and high NRR with a strong tendency towards a higher expression ofmiRNAs in bulls with moderate fertility. Thus, bulls with a moderate NRR negatively regulate the expression of protein-coding genes, which leads to problems during the pregnancy.

Endometrial cancer (EC) is the most frequently diagnosed gynecological malignancy and the fourth ... more 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.

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.org webcite.

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).

BACKGROUND: With the advent of microarray technology, it has become feasible to identify virtuall... more BACKGROUND: With the advent of microarray technology, it has become feasible to identify virtually all genes in an organism that are induced by developmental or environmental changes. However, relying solely on gene expression data may be of limited value if the aim is to infer the underlying genetic networks. Development of computational methods to combine microarray data with other information sources is therefore necessary. Here we describe one such method.RESULTS: By means of our method, previously published Arabidopsis microarray data from cold acclimated plants at six different time points, promoter motif sequence data extracted from approximately 24,000 Arabidopsis promoters and known transcription factor binding sites were combined to construct a putative genetic regulatory interaction network. The inferred network includes both previously characterised and hitherto un-described regulatory interactions between transcription factor (TF) genes and genes that encode other TFs or other proteins. Part of the obtained transcription factor regulatory network is presented here. More detailed information is available in the additional files.CONCLUSION: The rule-based method described here can be used to infer genetic networks by combining data from microarrays, promoter sequences and known promoter binding sites. This method should in principle be applicable to any biological system. We tested the method on the cold acclimation process in Arabidopsis and could identify a more complex putative genetic regulatory network than previously described. However, it should be noted that information on specific binding sites for individual TFs were in most cases not available. Thus, gene targets for the entire TF gene families were predicted. In addition, the networks were built solely by a bioinformatics approach and experimental verifications will be necessary for their final validation. On the other hand, since our method highlights putative novel interactions, more directed experiments could now be performed.

MicroRNAs are small non-coding RNAs that play crucial roles in the pathogenesis of different canc... more 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.

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.

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.

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.

Cancer Genetics and Cytogenetics, 2007

Breast cancer is the most common malignancy among women and accounts for over one million new cas... more Breast cancer is the most common malignancy among women and accounts for over one million new cases worldwide per year. Lymph node-negative breast cancer patients are reputed as having a better prognosis than lymph node-positive ones. Around 20% of the lymph node-negative patients die within 10 years after diagnosis. To improve the prognostics of node-negative breast cancer, it is important to understand the underlying biologic mechanisms promoting survival, such as specific genetic changes in the tumor genome. In this study, CGH was applied to analyze 64 tumors from node-negative breast cancer patients to identify DNA copy number changes in chromosomes and chromosome regions that may be correlated to survival. The main findings show gains at 4q, 5q31 approximately qter, 6q12 approximately q16, and 12q14 approximately q22, as well as losses of 17p, 18p, and Xq, which were significantly more recurrent in tumors from deceased patients than in tumors from survivors. The average number of chromosomal changes was higher in the tumors from deceased compared to the survivor tumors. Our findings suggest that tumors with specific chromosomal aberrations at 4q, 5q31 approximately qter, 6q12 approximately q16, 12q14 approximately q22, 17p, 18p, and Xq result in an aggressive form of breast cancer and that these patients are predisposed to succumb to breast cancer.

BMC Cancer, 2008

Background: It is of great significance to find better markers to correctly distinguish between h... more Background: It is of great significance to find better markers to correctly distinguish between high-risk and low-risk breast cancer patients since the majority of breast cancer cases are at present being overtreated. Methods: 46 tumours from node-negative breast cancer patients were studied with gene expression microarrays. A t-test was carried out in order to find a set of genes where the expression might predict clinical outcome. Two classifiers were used for evaluation of the gene lists, a correlation-based classifier and a Voting Features Interval (VFI) classifier. We then evaluated the predictive accuracy of this expression signature on tumour sets from two similar studies on lymph-node negative patients. They had both developed gene expression signatures superior to current methods in classifying node-negative breast tumours. These two signatures were also tested on our material. Results: A list of 51 genes whose expression profiles could predict clinical outcome with high accuracy in our material (96% or 89% accuracy in cross-validation, depending on type of classifier) was developed. When tested on two independent data sets, the expression signature based on the 51 identified genes had good predictive qualities in one of the data sets (74% accuracy), whereas their predictive value on the other data set were poor, presumably due to the fact that only 23 of the 51 genes were found in that material. We also found that previously developed expression signatures could predict clinical outcome well to moderately well in our material (72% and 61%, respectively). Conclusion: The list of 51 genes derived in this study might have potential for clinical utility as a prognostic gene set, and may include candidate genes of potential relevance for clinical outcome in breast cancer. According to the predictions by this expression signature, 30 of the 46 patients may have benefited from different adjuvant treatment than they recieved. Trial registration: The research on these tumours was approved by the Medical Faculty Research Ethics Committee (Medicinska fakultetens forskningsetikkommitté, Göteborg, Sweden (S164-02)).

BMC cancer, Jan 2, 2016

MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and progression... more MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and progression. In a previous study we identified 138 miRNAs as differentially expressed in endometrial adenocarcinoma compared to normal tissues. One of these miRNAs was miRNA-34a, which regulates several genes involved in the Notch pathway, which is frequently altered in endometrial cancer. The aims of this study were to verify the differential expression of a subset of miRNAs and to scrutinize the regulatory role of mir-34a on the target genes NOTCH1 and DLL1. Twenty-five miRNAs that were previously identified as differentially expressed were subjected to further analysis using qPCR. To investigate the regulation of NOTCH1 and DLL1 by mir-34a, we designed gain- and loss-of-function experiments in Ishikawa and HEK293 cell lines by transfection with a synthetic mir-34a mimic and a mir-34a inhibitor. Of the 25 validated miRNAs, seven were down-regulated and 18 were up-regulated compared to normal endo...

Previous work on host-parasite genetic algorithms consists of specific algorithms, applied to sin... more Previous work on host-parasite genetic algorithms consists of specific algorithms, applied to single example problems. We attempt to design a simple host-parasite genetic algorithm (SHPGA), with the aim of obtaining an algorithm with broad applicability to a wide range of problems. We argue that the benefits of the simplicity of SHPGA are twofold: i) it allows empirical analysis of the performance of the algorithm and comparison with the performance of a corresponding noncoevolutionary GA; and, ii) if performance benefits are found, we can fairly safely attribute them specifically to the use of host-parasite coevolution.

Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent losses distal ... more Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent losses distal to TP53. Myo1c can tightly and specifically bind to PIP2, the substrate of Phos-phoinositide 3-kinase (PI3K), and to Rictor, suggesting a role for MYO1C in the PI3K pathway. This study was designed to examine MYO1C expression status in a panel of well-stratified endometrial carcinomas as well as to assess the biological significance of MYO1C as a tumor suppressor in vitro. We found a significant correlation between the tumor stage and lowered expression of MYO1C in endometrial carcinoma samples. In cell transfection experiments, we found a negative correlation between MYO1C expression and cell proliferation, and MYO1C silencing resulted in diminished cell migration and adhesion. Cells expressing excess of MYO1C had low basal level of phosphorylated protein kinase B (PKB, a.k.a. AKT) and cells with knocked down MYO1C expression showed a quicker phosphorylated AKT (pAKT) response in reaction to serum stimulation. Taken together the present study gives further evidence for tumor suppressor activity of MYO1C and suggests MYO1C mediates its tumor suppressor function through inhibition of PI3K pathway and its involvement in loss of contact inhibition.

Background: In humans, muscle-specific nicotinergic acetylcholine receptor (AChR) is a transmembr... more Background: In humans, muscle-specific nicotinergic acetylcholine receptor (AChR) is a transmembrane protein with five different subunits, coded by CHRNA1, CHRNB, CHRND and CHRNG/CHRNE. The gamma subunit of AChR encoded by CHRNG is expressed during early foetal development, whereas in the adult, the γ subunit is replaced by a ε subunit. Mutations in the CHRNG encoding the embryonal acetylcholine receptor may cause the non-lethal Escobar variant (EVMPS) and lethal form (LMPS) of multiple pterygium syndrome. The MPS is a condition characterised by prenatal growth failure with pterygium and akinesia leading to muscle weakness and severe congenital contractures, as well as scoliosis. Results: Our whole exome sequencing studies have identified one novel and two previously reported homozygous mutations in CHRNG in three families affected by non-lethal EVMPS. The mutations consist of deletion of two nucleotides, cause a frameshift predicted to result in premature termination of the foetally expressed gamma subunit of the AChR.

Previously, we reported a chromium-resistant bacterium, Enterobacter cloacae B2-DHA, isolated fro... more Previously, we reported a chromium-resistant bacterium, Enterobacter cloacae B2-DHA, isolated from the landfills of tannery industries in Bangladesh. Here, we investigated its genetic composition using massively parallel sequencing and comparative analysis with other known Enterobacter genomes. Assembly of the sequencing reads revealed a genome of ~4.21 Mb in size.

Background: MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and... more Background: MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and progression. In a previous study we identified 138 miRNAs as differentially expressed in endometrial adenocarcinoma compared to normal tissues. One of these miRNAs was miRNA-34a, which regulates several genes involved in the Notch pathway, which is frequently altered in endometrial cancer. The aims of this study were to verify the differential expression of a subset of miRNAs and to scrutinize the regulatory role of mir-34a on the target genes NOTCH1 and DLL1.

Here, we report the genomic sequence and genetic composition of an arsenic-resistant bacterium, L... more Here, we report the genomic sequence and genetic composition of an arsenic-resistant bacterium, Lysinibacillus sphaericus B1-CDA. Assembly of the sequencing reads revealed that the genome size is ~4.5 Mb, encompassing ~80% of the chromosomal DNA.

Human pluripotent stem cells-(hPSCs-) derived hepatocytes have the potential to replace many hepa... more Human pluripotent stem cells-(hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models.

This study is a part of our long term project on bioremediation of toxic metals and other polluta... more This study is a part of our long term project on bioremediation of toxic metals and other pollutants for protection of human health and the environment from severe contamination. The information and results presented in this data article are based on both in vitro and in silico experiments. In vitro experiments were used to investigate the presence of arsenic responsive

contributed equally to this work. We report the 5,728,255-bp draft genome sequence of Rhodococcus... more contributed equally to this work. We report the 5,728,255-bp draft genome sequence of Rhodococcus ruber P25, isolated from a soil polluted with halogenated aromatic compounds in the city of Perm, Russia. The strain degrades polychlorinated biphenyls and a broad range of aromatic compounds. It possesses genes that mediate the degradation of biphenyls/polychlorinated biphenyls, naphthalene, and mono-aromatic compounds.

Chromium and chromium containing compounds are discharged into the nature as waste from anthropog... more Chromium and chromium containing compounds are discharged into the nature as waste from anthropogenic activities, such as industries, agriculture, forest farming, mining and metallurgy. Continued disposal of these compounds to the environment leads to development of various lethal diseases in both humans and animals. In this paper, we report a soil borne bacterium, B2-DHA that can be used as a vehicle to effectively remove chromium from the contaminated sources. B2-DHA is resistant to chromium with a MIC value of 1000 mg mL ¡1 potassium chromate. The bacterium has been identified as a Gram negative, Enterobacter cloacae based on biochemical characteristics and 16S rRNA gene analysis. TOF-SIMS and ICP-MS analyses confirmed intracellular accumulation of chromium and thus its removal from the contaminated liquid medium. Chromium accumulation in cells was 320 mg/g of cells dry biomass after 120-h exposure, and thus it reduced the chromium concentration in the liquid medium by as much as 81%. Environmental scanning electron micrograph revealed the effect of metals on cellular morphology of the isolates. Altogether, our results indicate that B2-DHA has the potential to reduce chromium significantly to safe levels from the contaminated environments and suggest the potential use of this bacterium in reducing human exposure to chromium, hence avoiding poisoning.

In silico prediction of novel miRNAs from genomic sequences remains a challenging problem. This s... more 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.

Lecture Notes in Computer Science, 2014

The significance of miRNAs has been clarified over the last decade as thousands of these small no... more 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 non-miRNAs. 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.

Cancer Informatics, 2013

We present a novel machine learning approach for the classification of cancer samples using expre... more 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.

Bull spermatozoa are rich in active miRNAs, and it has been shown that specific spermborne miRNAs... more Bull spermatozoa are rich in active miRNAs, and it has been
shown that specific spermborne miRNAs can be linked to
fertility. Thus, expression profiling of spermatozoa could be
helpful for understanding male fertility and the ability of
spermatozoa to initiate and sustain zygotic, embryonic and
foetal development. Herein we hypothesized that bulls with
moderate to high fertility can be identified by differences in
amounts of certain miRNAs between their ejaculates. RNA
samples from spermatozoa of eight brother pairs (one bull with
high and one with moderate NRR in each pair) of the Holstein
breed were prepared. miRNA was isolated, and the expression
of 178 miRNAs was determined by RT-qPCR. Important
findings were that highly expressed miRNAs, not linked toNRR
status, were identified in the bull sperm samples, which indicate
that these miRNAs have an important role in early embryogenesis. A large fraction of the targets genes were phosphoproteins and genes involved in the regulation of transcription. Seven miRNAs (mir-502-5p, mir-1249, mir-320a, mir-34c-3p, mir-19b-3p, mir-27a-5p and mir-148b-3p) were differentially expressed between bulls with moderate and high NRR with a strong tendency towards a higher expression ofmiRNAs in bulls with moderate fertility. Thus, bulls with a moderate NRR negatively regulate the expression of protein-coding genes, which leads to problems during the pregnancy.

Endometrial cancer (EC) is the most frequently diagnosed gynecological malignancy and the fourth ... more 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.

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.org webcite.

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).

BACKGROUND: With the advent of microarray technology, it has become feasible to identify virtuall... more BACKGROUND: With the advent of microarray technology, it has become feasible to identify virtually all genes in an organism that are induced by developmental or environmental changes. However, relying solely on gene expression data may be of limited value if the aim is to infer the underlying genetic networks. Development of computational methods to combine microarray data with other information sources is therefore necessary. Here we describe one such method.RESULTS: By means of our method, previously published Arabidopsis microarray data from cold acclimated plants at six different time points, promoter motif sequence data extracted from approximately 24,000 Arabidopsis promoters and known transcription factor binding sites were combined to construct a putative genetic regulatory interaction network. The inferred network includes both previously characterised and hitherto un-described regulatory interactions between transcription factor (TF) genes and genes that encode other TFs or other proteins. Part of the obtained transcription factor regulatory network is presented here. More detailed information is available in the additional files.CONCLUSION: The rule-based method described here can be used to infer genetic networks by combining data from microarrays, promoter sequences and known promoter binding sites. This method should in principle be applicable to any biological system. We tested the method on the cold acclimation process in Arabidopsis and could identify a more complex putative genetic regulatory network than previously described. However, it should be noted that information on specific binding sites for individual TFs were in most cases not available. Thus, gene targets for the entire TF gene families were predicted. In addition, the networks were built solely by a bioinformatics approach and experimental verifications will be necessary for their final validation. On the other hand, since our method highlights putative novel interactions, more directed experiments could now be performed.

MicroRNAs are small non-coding RNAs that play crucial roles in the pathogenesis of different canc... more 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.

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.

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.

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.