Clarissa P. C. Gomes

University of Luxembourg

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Rejko Krüger

Luxembourg Institute of Health

Lukas Pavelka

Luxembourg Institute of Health

Octávio Luiz Franco

Universidade Católica Dom Bosco

Tainá M. Marques

University of Luxembourg

Patrick May

University of Luxembourg

Rinaldo Wellerson Pereira

Universidade Católica de Brasília

Gloria Aguayo

Luxembourg Institute of Health

Venkata Satagopam

University of Luxembourg

Enrico Glaab

University of Luxembourg

Michel Vaillant

Luxembourg Institute of Health

Cooperative Institutions

University of Luxembourg

220

Luxembourg Institute of Health

219

Centre Hospitalier de Luxembourg

108

Laboratoire National de Santé

Inserm

Universidade Católica de Brasília

National Library of Luxembourg

Universidade de Brasília

Central Bank of Luxembourg

Maastricht University Medical Centre

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CyTOF and Flow Cytometry dataset assocaited with "Early-to-mid stage idiopathic Parkinson's disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females"

Zenodo (CERN European Organization for Nuclear Research) (2023)

Christophe Capelle Séverine Ciré Fanny Hedin Maxime Hansen Lukas Pavelka

This dataset contains all the raw mass cytometry (CyTOF) and flow cytometry fcs files associated with Capelle et al. 'Early-to-mid stage idiopathic Parkinson's disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females', Nature Communications, 2023, In Press. The dataset contains the following information: 1, The folder " CoPImmunoPD Flow Zenodo V2.zip " contains all the raw fcs files of flow cytometry analysis and the excel table with marker information of five staining panels in the initial discovery analysis using fresh blood samples. The folder also includes the fcs files of analyzing cytotoxicity potential within CD8 T cells and of validation analyses using cryopreserved samples. Single-color/fluorochrome staining files have also been provided for the relevant experiments in the given subfolders for compensation. 2, The folder "CoPImmunoPD_CyTOF_Zenodo.zip" contains all the raw fcs files generated from the CyTOF measurements in the initial discovery analysis. To reproduce our published Figures, please be assure to first read all the accompanied readme/excel information annotation files deposited in the corresponding folders within the zip files, all the Source Data files of different main and supplementary Figure subpanels, Methods and/or any other relevant sections in our manuscript.

10.5281/zenodo.8382969

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Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa‐Induced Dyskinesia

Movement Disorders (2024)

Yuri L. Sosero Sara Bandrés‐Ciga Bart Ferwerda Maria Teresa Periñan Tocino Dìaz R. Belloso

Abstract Background Levodopa‐induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2 . Objectives Our goal was to investigate the effects of genetic variants on risk and time to LID. Methods We performed a genome‐wide association study (GWAS) and analyses focused on GBA1 and LRRK2 variants. We also calculated polygenic risk scores (PRS) including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1612 PD patients with and 3175 without LID. Results We found that GBA1 variants were associated with LID risk (odds ratio [OR] = 1.65; 95% confidence interval [CI], 1.21–2.26; P = 0.0017) and LRRK2 variants with reduced time to LID onset (hazard ratio [HR] = 1.42; 95% CI, 1.09–1.84; P = 0.0098). The fourth quartile of the PD PRS was associated with increased LID risk (OR fourth_quartile = 1.27; 95% CI, 1.03–1.56; P = 0.0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HR third_quartile = 1.38; 95% CI, 1.07–1.79; P = 0.0128; HR fourth_quartile = 1.38; 95% CI = 1.06–1.78; P = 0.0147). Conclusions This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

LRRK2

Quartile

Genome-wide Association Study

10.1002/mds.29960

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Citations (1)

The implications on clinical diagnostics of using microRNA-based biomarkers in exercise

Expert Review of Molecular Diagnostics (2015)

Clarissa P. C. Gomes Taek‐Kyun Kim Kai Wang Yuqing He

Regular exercise is one of the best ways to maintain health and to prevent and control several chronic diseases. Identifying the molecular mechanisms associated with benefits of exercise is crucial and miRNAs have been suggested to be key players. Understanding the roles of miRNAs in these processes provides an opportunity to improve the clinical application of using exercise as a therapeutic intervention. Circulating miRNAs particularly are promising candidates for non-invasive biomarkers, which would enable oriented interventions. Furthermore, better and easier ways to assess exercise capacity can impact exercise evaluations and prescriptions, minimizing risks and monitoring the exercise response better. This review summarizes the current knowledge of miRNAs, recent advancements in miRNAs associated with exercise and addresses their role as biomarkers for exercise-related biological responses.

Biomarker Discovery

10.1586/14737159.2015.1039517

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The Function and Therapeutic Potential of Long Non-coding RNAs in Cardiovascular Development and Disease

Molecular Therapy — Nucleic Acids (2017)

Clarissa P. C. Gomes Helen Spencer K L Ford Lauriane Y. M. Michel Andrew H. Baker

The popularization of genome-wide analyses and RNA sequencing led to the discovery that a large part of the human genome, while effectively transcribed, does not encode proteins. Long non-coding RNAs have emerged as critical regulators of gene expression in both normal and disease states. Studies of long non-coding RNAs expressed in the heart, in combination with gene association studies, revealed that these molecules are regulated during cardiovascular development and disease. Some long non-coding RNAs have been functionally implicated in cardiac pathophysiology and constitute potential therapeutic targets. Here, we review the current knowledge of the function of long non-coding RNAs in the cardiovascular system, with an emphasis on cardiovascular development and biology, focusing on hypertension, coronary artery disease, myocardial infarction, ischemia, and heart failure. We discuss potential therapeutic implications and the challenges of long non-coding RNA research, with directions for future research and translational focus.

ENCODE

10.1016/j.omtn.2017.07.014

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Citations (102)

TRACE ELEMENT ANALYSIS OF PROTEINS DIRECTLY FROM 2D-PAGE: AN EFFICIENT STRATEGY FOR METALLOPROTEOMICS

Preparative Biochemistry & Biotechnology (2011)

Clarissa P. C. Gomes Mirna S. Freire Octávio Luiz Franco

Inductively coupled plasma-mass spectrometry (ICP-MS) is a sensitive analytical method to detect the total concentrations of elements in biological samples, but it is unable to identify molecules that can bind to metals, and for this reason it is vital to combine this method's use with other biochemical techniques. Therefore, in order to identify elements complexed to specific proteins, a very relevant combination of bidimensional electrophoresis followed by ICP-MS was used. Protein spots from gels were excised and submitted directly to element detection, a method not reported before. This report focused on the use of plasma from people with laryngeal carcinoma. Most elements were below detection level, with only Cr and Pb being observed in all samples. Although the relationship between metals and laryngeal cancer was not conclusive, it is possible to affirm that the methodology utilized here is successful and has the advantage of determining to which proteins the elements bind.

Trace element

TRACE (psycholinguistics)

10.1080/10826068.2011.575272

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Creation of a pandemic memory by tracing COVID-19 infections and immunity in Luxembourg (CON-VINCE)

BMC Infectious Diseases (2024)

Olena Tsurkalenko Dmitry Bulaev Marc Paul O’Sullivan Chantal J. Snoeck Soumyabrata Ghosh

Abstract Background During the COVID-19 pandemic swift implementation of research cohorts was key. While many studies focused exclusively on infected individuals, population based cohorts are essential for the follow-up of SARS-CoV-2 impact on public health. Here we present the CON-VINCE cohort, estimate the point and period prevalence of the SARS-CoV-2 infection, reflect on the spread within the Luxembourgish population, examine immune responses to SARS-CoV-2 infection and vaccination, and ascertain the impact of the pandemic on population psychological wellbeing at a nationwide level. Methods A representative sample of the adult Luxembourgish population was enrolled. The cohort was followed-up for twelve months. SARS-CoV-2 RT-qPCR and serology were conducted at each sampling visit. The surveys included detailed epidemiological, clinical, socio-economic, and psychological data. Results One thousand eight hundred sixty-five individuals were followed over seven visits (April 2020—June 2021) with the final weighted period prevalence of SARS-CoV-2 infection of 15%. The participants had similar risks of being infected regardless of their gender, age, employment status and education level. Vaccination increased the chances of IgG-S positivity in infected individuals. Depression, anxiety, loneliness and stress levels increased at a point of study when there were strict containment measures, returning to baseline afterwards. Conclusion The data collected in CON-VINCE study allowed obtaining insights into the infection spread in Luxembourg, immunity build-up and the impact of the pandemic on psychological wellbeing of the population. Moreover, the study holds great translational potential, as samples stored at the biobank, together with self-reported questionnaire information, can be exploited in further research. Trial registration Trial registration number: NCT04379297, 10 April 2020.

Pandemic

Herd Immunity

10.1186/s12879-024-09055-z

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Citations (2)

Early-to-mid stage idiopathic Parkinson’s disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females

Nature Communications (2023)

Christophe Capelle Séverine Ciré Fanny Hedin Maxime Hansen Lukas Pavelka

Neuroinflammation in the brain contributes to the pathogenesis of Parkinson's disease (PD), but the potential dysregulation of peripheral immunity has not been systematically investigated for idiopathic PD (iPD). Here we showed an elevated peripheral cytotoxic immune milieu, with more terminally-differentiated effector memory (TEMRA) CD8 T, CD8+ NKT cells and circulating cytotoxic molecules in fresh blood of patients with early-to-mid iPD, especially females, after analyzing > 700 innate and adaptive immune features. This profile, also reflected by fewer CD8+FOXP3+ T cells, was confirmed in another subcohort. Co-expression between cytotoxic molecules was selectively enhanced in CD8 TEMRA and effector memory (TEM) cells. Single-cell RNA-sequencing analysis demonstrated the accelerated differentiation within CD8 compartments, enhanced cytotoxic pathways in CD8 TEMRA and TEM cells, while CD8 central memory (TCM) and naïve cells were already more-active and transcriptionally-reprogrammed. Our work provides a comprehensive map of dysregulated peripheral immunity in iPD, proposing candidates for early diagnosis and treatments.

10.1038/s41467-023-43053-0

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Exercise induction of gut microbiota modifications in obese, non-obese and hypertensive rats

BMC Genomics (2014)

Bernardo Petriz Alinne Pereira de Castro Jeeser Alves de Almeida Clarissa P. C. Gomes Gabriel da Rocha Fernandes

Obesity is a multifactor disease associated with cardiovascular disorders such as hypertension. Recently, gut microbiota was linked to obesity pathogenesisand shown to influence the host metabolism. Moreover, several factors such as host-genotype and life-style have been shown to modulate gut microbiota composition. Exercise is a well-known agent used for the treatment of numerous pathologies, such as obesity and hypertension; it has recently been demonstrated to shape gut microbiota consortia. Since exercise-altered microbiota could possibly improve the treatment of diseases related to dysfunctional microbiota, this study aimed to examine the effect of controlled exercise training on gut microbial composition in Obese rats (n = 3), non-obese Wistar rats (n = 3) and Spontaneously Hypertensive rats (n = 3). Pyrosequencing of 16S rRNA genes from fecal samples collected before and after exercise training was used for this purpose. Exercise altered the composition and diversity of gut bacteria at genus level in all rat lineages. Allobaculum (Hypertensive rats), Pseudomonas and Lactobacillus (Obese rats) were shown to be enriched after exercise, while Streptococcus (Wistar rats), Aggregatibacter and Sutturella (Hypertensive rats) were more enhanced before exercise. A significant correlation was seen in the Clostridiaceae and Bacteroidaceae families and Oscillospira and Ruminococcus genera with blood lactate accumulation. Moreover, Wistar and Hypertensive rats were shown to share a similar microbiota composition, as opposed to Obese rats. Finally, Streptococcus alactolyticus, Bifidobacterium animalis, Ruminococcus gnavus, Aggregatibacter pneumotropica and Bifidobacterium pseudolongum were enriched in Obese rats. These data indicate that non-obese and hypertensive rats harbor a different gut microbiota from obese rats and that exercise training alters gut microbiota from an obese and hypertensive genotype background.

10.1186/1471-2164-15-511

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Accurate long-read sequencing identified GBA1 as major risk factor in the Luxembourgish Parkinson’s study

npj Parkinson s Disease (2023)

Sinthuja Pachchek Zied Landoulsi Lukas Pavelka Claudia Schulte Elena Buena‐Atienza

Abstract Heterozygous variants in the glucocerebrosidase GBA1 gene are an increasingly recognized risk factor for Parkinson’s disease (PD). Due to the GBAP1 pseudogene, which shares 96% sequence homology with the GBA1 coding region, accurate variant calling by array-based or short-read sequencing methods remains a major challenge in understanding the genetic landscape of GBA1 -associated PD. We analyzed 660 patients with PD, 100 patients with Parkinsonism and 808 healthy controls from the Luxembourg Parkinson’s study, sequenced using amplicon-based long-read DNA sequencing technology. We found that 12.1% (77/637) of PD patients carried GBA1 variants, with 10.5% (67/637) of them carrying known pathogenic variants (including severe, mild, risk variants). In comparison, 5% (34/675) of the healthy controls carried GBA1 variants, and among them, 4.3% (29/675) were identified as pathogenic variant carriers. We found four GBA1 variants in patients with atypical parkinsonism. Pathogenic GBA1 variants were 2.6-fold more frequently observed in PD patients compared to controls (OR = 2.6; CI = [1.6,4.1]). Three novel variants of unknown significance (VUS) were identified. Using a structure-based approach, we defined a potential risk prediction method for VUS. This study describes the full landscape of GBA1 -related parkinsonism in Luxembourg, showing a high prevalence of GBA1 variants as the major genetic risk for PD. Although the long-read DNA sequencing technique used in our study may be limited in its effectiveness to detect potential structural variants, our approach provides an important advancement for highly accurate GBA1 variant calling, which is essential for providing access to emerging causative therapies for GBA1 carriers.

Pseudogene

10.1038/s41531-023-00595-w

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A Review of Computational Tools in microRNA Discovery

Frontiers in Genetics (2013)

Clarissa P. C. Gomes Ji‐Hoon Cho Leroy Hood Octávio Luiz Franco Rinaldo Wellerson Pereira

REVIEW article Front. Genet., 15 May 2013Sec. Computational Genomics Volume 4 - 2013 | https://doi.org/10.3389/fgene.2013.00081

Computational genomics

10.3389/fgene.2013.00081

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Citations (103)