To Örebro University

oru.seÖrebro University Publications
Change search
Link to record
Permanent link

Direct link
Alternative names
Publications (10 of 33) Show all publications
Koskela, A., Lindqvist, C. M., Asghar, N., Johansson, M., Sundqvist, M., Mölling, P. & Stenmark, B. (2023). Comparison of SARS-CoV-2 whole genome sequencing using tiled amplicon enrichment and bait hybridization. In: : . Paper presented at Smögen Virology Symposium 2023, Smögen, Sweden, August 24-26, 2023..
Open this publication in new window or tab >>Comparison of SARS-CoV-2 whole genome sequencing using tiled amplicon enrichment and bait hybridization
Show others...
2023 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) worldwide pandemic has led to extensive virological monitoring by whole genome sequencing (WGS). Investigating the advantages and limitations of different protocols is key when conducting population-level WGS. SARS-CoV-2 positive samples with Ct values of 14–30 were run using three different protocols: the Twist Bioscience SARS‑CoV‑2 protocol with bait hybridization enrichment sequenced with Illumina, and two tiled amplicon enrichment protocols, ARTIC V3 and Midnight, sequenced with Illumina and Oxford Nanopore Technologies, respectively. Twist resulted in better coverage uniformity and coverage of the entire genome, but has several drawbacks: high human contamination, laborious workflow, high cost, and variation between batches. The ARTIC and Midnight protocol produced an even coverage across samples, and almost all reads were mapped to the SARS-CoV-2 reference. ARTIC and Midnight represent robust, cost-effective, and highly scalable methods that are appropriate in a clinical environment. Lineage designations were uniform across methods, representing the dominant lineages in Sweden during the period of collection. This study provides insights into methodological differences in SARS‑CoV‑2 sequencing and guidance in selecting suitable methods for various purposes.

National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-108004 (URN)
Conference
Smögen Virology Symposium 2023, Smögen, Sweden, August 24-26, 2023.
Available from: 2023-09-01 Created: 2023-09-01 Last updated: 2023-09-05Bibliographically approved
Koskela, A., Lindqvist, C. M., Asghar, N., Johansson, M., Sundqvist, M., Mölling, P. & Stenmark, B. (2023). Comparison of SARS-CoV-2 whole genome sequencing using tiled amplicon enrichment and bait hybridization. Scientific Reports, 13(1), Article ID 6461.
Open this publication in new window or tab >>Comparison of SARS-CoV-2 whole genome sequencing using tiled amplicon enrichment and bait hybridization
Show others...
2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 6461Article in journal (Refereed) Published
Abstract [en]

The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) pandemic has led to extensive virological monitoring by whole genome sequencing (WGS). Investigating the advantages and limitations of different protocols is key when conducting population-level WGS. SARS-CoV-2 positive samples with Ct values of 14-30 were run using three different protocols: the Twist Bioscience SARS‑CoV‑2 protocol with bait hybridization enrichment sequenced with Illumina, and two tiled amplicon enrichment protocols, ARTIC V3 and Midnight, sequenced with Illumina and Oxford Nanopore Technologies, respectively. Twist resulted in better coverage uniformity and coverage of the entire genome, but has several drawbacks: high human contamination, laborious workflow, high cost, and variation between batches. The ARTIC and Midnight protocol produced an even coverage across samples, and almost all reads were mapped to the SARS-CoV-2 reference. ARTIC and Midnight represent robust, cost-effective, and highly scalable methods that are appropriate in a clinical environment. Lineage designations were uniform across methods, representing the dominant lineages in Sweden during the period of collection. This study provides insights into methodological differences in SARS‑CoV‑2 sequencing and guidance in selecting suitable methods for various purposes.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-105616 (URN)10.1038/s41598-023-33168-1 (DOI)001025198300001 ()37081087 (PubMedID)2-s2.0-85153442204 (Scopus ID)
Funder
Region Örebro CountyÖrebro University
Available from: 2023-04-21 Created: 2023-04-21 Last updated: 2023-09-05Bibliographically approved
Eriksson, L., Johannesen, T. B., Stenmark, B., Jacobsson, S., Säll, O., Hedberg, S. T., . . . Mölling, P. (2023). Genetic variants linked to the phenotypic outcome of invasive disease and carriage of Neisseria meningitidis. Microbial Genomics, 9(10)
Open this publication in new window or tab >>Genetic variants linked to the phenotypic outcome of invasive disease and carriage of Neisseria meningitidis
Show others...
2023 (English)In: Microbial Genomics, E-ISSN 2057-5858, Vol. 9, no 10Article in journal (Refereed) Published
Abstract [en]

Neisseria meningitidis can be a human commensal in the upper respiratory tract but is also capable of causing invasive diseases such as meningococcal meningitis and septicaemia. No specific genetic markers have been detected to distinguish carriage from disease isolates. The aim here was to find genetic traits that could be linked to phenotypic outcomes associated with carriage versus invasive N. meningitidis disease through a bacterial genome-wide association study (GWAS). In this study, invasive N. meningitidis isolates collected in Sweden (n=103) and carriage isolates collected at Örebro University, Sweden (n=213) 2018-2019 were analysed. The GWAS analysis, treeWAS, was applied to single-nucleotide polymorphisms (SNPs), genes and k-mers. One gene and one non-synonymous SNP were associated with invasive disease and seven genes and one non-synonymous SNP were associated with carriage isolates. The gene associated with invasive disease encodes a phage transposase (NEIS1048), and the associated invasive SNP glmU S373C encodes the enzyme N-acetylglucosamine 1-phosphate (GlcNAC 1-P) uridyltransferase. Of the genes associated with carriage isolates, a gene variant of porB encoding PorB class 3, the genes pilE/pilS and tspB have known functions. The SNP associated with carriage was fkbp D33N, encoding a FK506-binding protein (FKBP). K-mers from PilS, tbpB and tspB were found to be associated with carriage, while k-mers from mtrD and tbpA were associated with invasiveness. In the genes fkbp, glmU, PilC and pilE, k-mers were found that were associated with both carriage and invasive isolates, indicating that specific variations within these genes could play a role in invasiveness. The data presented here highlight genetic traits that are significantly associated with invasive or carriage N. meningitidis across the species population. These traits could prove essential to our understanding of the pathogenicity of N. meningitidis and could help to identify future vaccine targets.

Place, publisher, year, edition, pages
Microbiology Society, 2023
Keywords
Carriage, Genome-wide association study, Invasive meningococcal disease, Neisseria meningitidis
National Category
Medical Genetics
Identifiers
urn:nbn:se:oru:diva-109425 (URN)10.1099/mgen.0.001124 (DOI)001107086200005 ()37874326 (PubMedID)2-s2.0-85175126623 (Scopus ID)
Funder
Region Örebro County, OLL-967424
Available from: 2023-10-25 Created: 2023-10-25 Last updated: 2024-01-22Bibliographically approved
Säll, O., Eriksson, L., Idosa Berhane, A., Persson, A., Magnuson, A., Thulin Hedberg, S., . . . Jacobsson, S. (2023). Prevalence and persistence of Neisseria meningitidis carriage in Swedish university students. Epidemiology and Infection, 151, Article ID e25.
Open this publication in new window or tab >>Prevalence and persistence of Neisseria meningitidis carriage in Swedish university students
Show others...
2023 (English)In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 151, article id e25Article in journal (Refereed) Published
Abstract [en]

The bacterium Neisseria meningitidis causes life-threatening disease worldwide, typically with a clinical presentation of sepsis or meningitis, but can be carried asymptomatically as part of the normal human oropharyngeal microbiota. The aim of this study was to examine N. meningitidis carriage with regard to prevalence, risk factors for carriage, distribution of meningococcal lineages and persistence of meningococcal carriage. Throat samples and data from a self-reported questionnaire were obtained from 2744 university students (median age: 23 years) at a university in Sweden on four occasions during a 12-month period. Meningococcal isolates were characterised using whole-genome sequencing. The carriage rate among the students was 9.1% (319/3488; 95% CI 8.2-10.1). Factors associated with higher carriage rate were age ≤22 years, previous tonsillectomy, cigarette smoking, drinking alcohol and attending parties, pubs and clubs. Female gender and sharing a household with children aged 0-9 years were associated with lower carriage. The most frequent genogroups were capsule null locus (cnl), group B and group Y and the most commonly identified clonal complexes (cc) were cc198 and cc23. Persistent carriage with the same meningococcal strain for 12 months was observed in two students. Follow-up times exceeding 12 months are recommended for future studies investigating long-term carriage of N. meningitidis.

Place, publisher, year, edition, pages
Cambridge University Press, 2023
Keywords
Carriage, Neisseria meningitidis, Swedish snus, university students, whole genome sequencing
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:oru:diva-104135 (URN)10.1017/S0950268823000018 (DOI)000930011500001 ()36775828 (PubMedID)2-s2.0-85147835011 (Scopus ID)
Available from: 2023-02-13 Created: 2023-02-13 Last updated: 2023-03-16Bibliographically approved
Fioretos, T., Wirta, V., Cavelier, L., Berglund, E., Friedman, M., Akhras, M., . . . Rosenquist, R. (2022). Implementing precision medicine in a regionally organized healthcare system in Sweden [Letter to the editor]. Nature Medicine, 28(10), 1980-1982
Open this publication in new window or tab >>Implementing precision medicine in a regionally organized healthcare system in Sweden
Show others...
2022 (English)In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 28, no 10, p. 1980-1982Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Nature Publishing Group, 2022
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:oru:diva-101431 (URN)10.1038/s41591-022-01963-4 (DOI)000857867600001 ()36123428 (PubMedID)2-s2.0-85138201780 (Scopus ID)
Note

Funding agencies:

SciLifeLab 

Medical faculty at Gothenburg University

Medical faculty at Linköping University

Medical faculty at Lund University

Medical faculty at Karolinska Institutet 

Available from: 2022-09-23 Created: 2022-09-23 Last updated: 2022-10-26Bibliographically approved
Säll, O., Stenmark, B., Jacobsson, S., Eriksson, L., Thulin Hedberg, S., Hertting, O., . . . Mölling, P. (2021). Atypical presentation of Neisseria meningitidis serogroup W disease is associated with the introduction of the 2013 strain. Epidemiology and Infection, 149, Article ID e126.
Open this publication in new window or tab >>Atypical presentation of Neisseria meningitidis serogroup W disease is associated with the introduction of the 2013 strain
Show others...
2021 (English)In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 149, article id e126Article in journal (Refereed) Published
Abstract [en]

Since 2015, the incidence of invasive meningococcal disease (IMD) caused by serogroup W (MenW) has increased in Sweden, due to the introduction of the 2013 strain belonging to clonal complex 11. The aim of this study was to describe the clinical presentation of MenW infections, in particular the 2013 strain, including genetic associations. Medical records of confirmed MenW IMD cases in Sweden during the years 1995-2019 (n = 113) were retrospectively reviewed and the clinical data analysed according to strain. Of all MenW patients, bacteraemia without the focus of infection was seen in 44%, bacteraemic pneumonia in 26%, meningitis in 13% and epiglottitis in 8%, gastrointestinal symptoms in 48% and 4% presented with petechiae. Phylogenetic analysis was used for possible links between genetic relationship and clinical picture. The 2013 strain infections, particularly in one cluster, were associated with more severe disease compared with other MenW infections. The patients with 2013 strain infections (n = 68) were older (52 years vs. 25 years for other strains), presented more often with diarrhoea as an atypical presentation (P = 0.045) and were more frequently admitted for intensive care (P = 0.032). There is a risk that the atypical clinical presentation of MenW infections, with predominantly gastrointestinal or respiratory symptoms rather than neck stiffness or petechiae, may lead to delay in life-saving treatment.

Place, publisher, year, edition, pages
Cambridge University Press, 2021
Keywords
Invasive meningococcal disease, meningococcal disease, Neisseria meningitidis, serogroup W, Sweden
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-91688 (URN)10.1017/S0950268821001035 (DOI)000652182800001 ()33910672 (PubMedID)
Note

Funding Agency:

Swedish state under the ALF  

Available from: 2021-05-10 Created: 2021-05-10 Last updated: 2023-06-30Bibliographically approved
Stenmark, B., Eriksson, L., Thulin Hedberg, S., Anton, B. P., Fomenkov, A., Roberts, R. J. & Mölling, P. (2021). Genome-wide methylome analysis of two strains belonging to the hypervirulent Neisseria meningitidis serogroup W ST-11 clonal complex. Scientific Reports, 11(1), Article ID 6239.
Open this publication in new window or tab >>Genome-wide methylome analysis of two strains belonging to the hypervirulent Neisseria meningitidis serogroup W ST-11 clonal complex
Show others...
2021 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 6239Article in journal (Refereed) Published
Abstract [en]

A rising incidence of meningococcal serogroup W disease has been evident in many countries worldwide. Serogroup W isolates belonging to the sequence type (ST)-11 clonal complex have been associated with atypical symptoms and increased case fatality rates. The continued expansion of this clonal complex in the later part of the 2010s has been largely due to a shift from the so-called original UK strain to the 2013 strain. Here we used single-molecule real-time (SMRT) sequencing to determine the methylomes of the two major serogroup W strains belonging to ST-11 clonal complex. Five methylated motifs were identified in this study, and three of the motifs, namely 5'-GATC-3', 5'-GAAGG-3', 5'-GCGCGC-3', were found in all 13 isolates investigated. The results showed no strain-specific motifs or difference in active restriction modification systems between the two strains. Two phase variable methylases were identified and the enrichment or depletion of the methylation motifs generated by these methylases varied between the two strains. Results from this work give further insight into the low diversity of methylomes in highly related strains and encourage further research to decipher the role of regions with under- or overrepresented methylation motifs.

Place, publisher, year, edition, pages
Nature Publishing Group, 2021
National Category
Microbiology
Identifiers
urn:nbn:se:oru:diva-90626 (URN)10.1038/s41598-021-85266-7 (DOI)000667581800039 ()33737546 (PubMedID)2-s2.0-85102697942 (Scopus ID)
Note

Funding Agency:

Örebro University 

Available from: 2021-03-22 Created: 2021-03-22 Last updated: 2022-09-15Bibliographically approved
Qvick, A., Stenmark, B., Carlsson, J., Isaksson, J., Karlsson, C. & Helenius, G. (2021). Liquid biopsy as an option for predictive testing and prognosis in patients with lung cancer. Molecular Medicine, 27(1), Article ID 68.
Open this publication in new window or tab >>Liquid biopsy as an option for predictive testing and prognosis in patients with lung cancer
Show others...
2021 (English)In: Molecular Medicine, ISSN 1076-1551, E-ISSN 1528-3658, Vol. 27, no 1, article id 68Article in journal (Refereed) Published
Abstract [en]

Background: The aim of this study was to investigate the clinical value of liquid biopsy as a primary source for variant analysis in lung cancer. In addition, we sought to characterize liquid biopsy variants and to correlate mutational load to clinical data.

Methods: Circulating cell-free DNA was extracted from plasma from patients with lung cancer (n = 60) and controls with benign lung disease (n = 16). Variant analysis was performed using the AVENIO ctDNA Surveillance kit and the results were correlated to clinical and variant analysis data from tumor tissue or cytology retrieved from clinical routine diagnostics.

Results: There were significantly more variants detected in lung cancer cases compared to controls (p = 0.011), but no difference between the histological subgroups of lung cancer was found (p = 0.465). Furthermore, significantly more variants were detected in patients with stage IIIb-IV disease compared to patients with stage I-IIIa (median 7 vs 4, p = 0.017). Plasma cfDNA mutational load was significantly associated with overall survival (p = 0.010). The association persisted when adjusted for stage and ECOG performance status (HR: 3.64, 95% CI 1.37-9.67, p = 0.009). Agreement between tumor and plasma samples significantly differed with stage; patients with stage IIIb-IV disease showed agreement in 88.2% of the cases with clinically relevant variants, compared to zero cases in stage I-IIIa (p = 0.004). Furthermore, one variant in EGFR, two in KRAS, and one in BRAF were detected in plasma but not in tumor samples.

Conclusion: This study concludes that in the vast majority of advanced NSCLC patients a reliable variant analysis can be performed using liquid biopsy from plasma. Furthermore, we found that the number of variants in plasma is associated with prognosis, possibly indicating a strategy for closer follow up on this crucial patient group.

Place, publisher, year, edition, pages
Springer, 2021
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-93189 (URN)10.1186/s10020-021-00331-1 (DOI)000669300200001 ()34217228 (PubMedID)2-s2.0-85110796418 (Scopus ID)
Note

Funding Agencies:

Örebro County Council Research committee  

Lions fund for cancer research Uppsala-Örebro  

Nyckelfonden-Örebro University Hospital Research Foundation  

Uppsala-Örebro Regional research council 

Available from: 2021-07-30 Created: 2021-07-30 Last updated: 2023-03-03Bibliographically approved
Stenmark, B., Harrison, O. B., Eriksson, L., Anton, B. P., Fomenkov, A., Roberts, R. J., . . . Mölling, P. (2020). Complete genome and methylome analysis of Neisseria meningitidis associated with increased serogroup Y disease. Scientific Reports, 10(1), Article ID 3644.
Open this publication in new window or tab >>Complete genome and methylome analysis of Neisseria meningitidis associated with increased serogroup Y disease
Show others...
2020 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 3644Article in journal (Refereed) Published
Abstract [en]

Invasive meningococcal disease (IMD) due to serogroup Y Neisseria meningitidis emerged in Europe during the 2000s. Draft genomes of serogroup Y isolates in Sweden revealed that although the population structure of these isolates was similar to other serogroup Y isolates internationally, a distinct strain (YI) and more specifically a sublineage (1) of this strain was responsible for the increase of serogroup Y IMD in Sweden. We performed single molecule real-time (SMRT) sequencing on eight serogroup Y isolates from different sublineages to unravel the genetic and epigenetic factors delineating them, in order to understand the serogroup Y emergence. Extensive comparisons between the serogroup Y sublineages of all coding sequences, complex genomic regions, intergenic regions, and methylation motifs revealed small point mutations in genes mainly encoding hypothetical and metabolic proteins, and non-synonymous variants in genes involved in adhesion, iron acquisition, and endotoxin production. The methylation motif CACNNNNNTAC was only found in isolates of sublineage 2. Only seven genes were putatively differentially expressed, and another two genes encoding hypothetical proteins were only present in sublineage 2. These data suggest that the serogroup Y IMD increase in Sweden was most probably due to small changes in genes important for colonization and transmission.

Place, publisher, year, edition, pages
Nature Publishing Group, 2020
National Category
Genetics
Identifiers
urn:nbn:se:oru:diva-80302 (URN)10.1038/s41598-020-59509-y (DOI)000563070300006 ()32108139 (PubMedID)2-s2.0-85080987210 (Scopus ID)
Funder
Wellcome trust, 218205/Z/19/Z 214374/Z/18/Z
Note

Funding Agencies:

"Functional Genomics" program of the Research Council of Norway  

"Infrastructure" program of the Research Council of Norway  

Southeastern Regional Health Authorities 

European Union (EU)

Örebro County Council Research Committee  

Nyckelfonden  

Örebro University 

Available from: 2020-03-03 Created: 2020-03-03 Last updated: 2022-09-15Bibliographically approved
Eriksson, L., Stenmark, B., Deghmane, A.-E., Thulin Hedberg, S., Säll, O., Fredlund, H., . . . Taha, M.-K. (2020). Difference in virulence between Neisseria meningitidis serogroups W and Y in transgenic mice. BMC Microbiology, 20(1), Article ID 92.
Open this publication in new window or tab >>Difference in virulence between Neisseria meningitidis serogroups W and Y in transgenic mice
Show others...
2020 (English)In: BMC Microbiology, E-ISSN 1471-2180, Vol. 20, no 1, article id 92Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Neisseria meningitidis serogroups W and Y are the most common serogroups causing invasive meningococcal disease in Sweden. The majority of cases are caused by the serogroup W UK 2013 strain of clonal complex (cc) 11, and subtype 1 of the serogroup Y, YI strain of cc23. In this study, virulence factors of several lineages within cc11 and cc23 were investigated in transgenic BALB/c mice expressing human transferrin. Transgenic mice were infected intraperitoneally with serogroup W and Y isolates. Levels of bacteria and the proinflammatory cytokine CXCL1 were determined in blood collected 3 h and 24 h post-infection. Apoptosis was investigated in immune cells from peritoneal washes of infected mice. Adhesion and induction of apoptosis in human epithelial cells were also scored.

RESULTS: The levels of bacteraemia, CXCL1, and apoptosis were higher in serogroup W infected mice than in serogroup Y infected mice. Serogroup W isolates also induced higher levels of apoptosis and adhesion in human epithelial cells. No significant differences were observed between different lineages within cc11 and cc23.

CONCLUSIONS: N. meningitidis Serogroup W displayed a higher virulence in vivo in transgenic mice, compared to serogroup Y. This was reflected by higher bacteremia, proinflammatory activity, and ability to induce apoptosis in mouse immune cells and human epithelial cells.

Place, publisher, year, edition, pages
BioMed Central, 2020
Keywords
Neisseria meningitidis, Serogroup W, Serogroup Y, Transgenic mice, Virulence
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-81345 (URN)10.1186/s12866-020-01760-4 (DOI)000528725400001 ()32295520 (PubMedID)2-s2.0-85083478167 (Scopus ID)
Note

Funding Agencies:

Örebro County Council Research Committee  

Nyckelfonden, Örebro University Hospital, Örebro, Sweden  

Institut Pasteur, Paris, France  

Örebro University 

Available from: 2020-04-29 Created: 2020-04-29 Last updated: 2024-01-17Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-4637-8626

Search in DiVA

Show all publications