Browsing by Author "Damien Chaussabel"

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    Blood gene transcript signature profiling in pregnancies resulting in preterm birth: A systematic review
    (2020-10-01) Tobias Brummaier; Basirudeen Syed Ahamed Kabeer; Damien Chaussabel; Jürg Utzinger; Rose McGready; Daniel H. Paris; Shoklo Malaria Research Unit; Universitat Basel; Swiss Tropical and Public Health Institute (Swiss TPH); Nuffield Department of Medicine; Sidra Medicine
    © 2020 The Author(s) Objective: To pursue a systematic review and summarise the current evidence for the potential of transcriptome molecular profiling in investigating the preterm phenotype. Study design: We systematically reviewed the literature, using readily available electronic databases (i.e. PubMed/Medline, Embase, Scopus and Web of Science) from inception until March 2020 to identify investigations of maternal blood-derived RNA profiling in preterm birth (PTB). Studies were included if circulating coding or non-coding RNA was analysed in maternal blood during pregnancy and/or at delivery. Interventional trials were not included. The primary outcome was the availability of whole genome expression patterns evaluated in pregnancies resulting in preterm deliveries. Results: A total of 35 articles were included in the final analysis. Most of the studies were conducted in high-income countries and published in the last decade. Apart from spontaneous PTB, a variety of phenotypes leading to preterm delivery were reported. Differences in sampling methods, target gene selection and laboratory protocols severely limited any quantitative comparisons. Most of the studies revealed that gene expression profiling during pregnancy has high potential for identifying women at risk of spontaneous and/or non-spontaneous PTB as early as in the first trimester. Conclusion: Assessing maternal blood-derived transcriptional signatures for PTB risk in pregnant women holds promise as a screening approach. However, longitudinally followed, prospective pregnancy cohorts are lacking. These are relevant for identifying causes leading to PTB and whether prediction of spontaneous PTB or co-morbidities associated with PTB is achievable. More emphasis on widely employed standardised protocols is required to ensure comparability of results.
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    Cohort profile: Molecular signature in pregnancy (MSP): Longitudinal high-frequency sampling to characterise cross-omic trajectories in pregnancy in a resource-constrained setting
    (2020-10-10) Tobias Brummaier; Basirudeen Syed Ahamed Kabeer; Pornpimon Wilaisrisak; Mupawjay Pimanpanarak; Aye Kyi Win; Sasithon Pukrittayakamee; Alexandra K. Marr; Tomoshige Kino; Souhaila Al Khodor; Annalisa Terranegra; Verena I. Carrara; Francois Nosten; Jürg Utzinger; Damien Chaussabel; Daniel H. Paris; Rose McGready; Shoklo Malaria Research Unit; Universitat Basel; Swiss Tropical and Public Health Institute (Swiss TPH); Mahidol University; Nuffield Department of Medicine; Sidra Medicine
    © Purpose A successful pregnancy relies on the interplay of various biological systems. Deviations from the norm within a system or intersystemic interactions may result in pregnancy-Associated complications and adverse pregnancy outcomes. Systems biology approaches provide an avenue of unbiased, in-depth phenotyping in health and disease. The molecular signature in pregnancy (MSP) cohort was established to characterise longitudinal, cross-omic trajectories in pregnant women from a resource constrained setting. Downstream analysis will focus on characterising physiological perturbations in uneventful pregnancies, pregnancy-Associated complications and adverse outcomes. Participants First trimester pregnant women of Karen or Burman ethnicity were followed prospectively throughout pregnancy, at delivery and until 3 months post partum. Serial high-frequency sampling to assess whole blood transcriptomics and microbiome composition of the gut, vagina and oral cavity, in conjunction with assessment of gene expression and microbial colonisation of gestational tissue, was done for all cohort participants. Findings to date 381 women with live born singletons averaged 16 (IQR 15-18) antenatal visits (13 094 biological samples were collected). At 5% (19/381) the preterm birth rate was low. Other adverse events such as maternal febrile illness 7.1% (27/381), gestational diabetes 13.1% (50/381), maternal anaemia 16.3% (62/381), maternal underweight 19.2% (73/381) and a neonate born small for gestational age 20.2% (77/381) were more often observed than preterm birth. Future plans Results from the MSP cohort will enable in-depth characterisation of cross-omic molecular trajectories in pregnancies from a population in a resource-constrained setting. Moreover, pregnancy-Associated complications and unfavourable pregnancy outcomes will be investigated at the same granular level, with a particular focus on population relevant needs such as effect of tropical infections on pregnancy. More detailed knowledge on multiomic perturbations will ideally result in the development of diagnostic tools and ultimately lead to targeted interventions that may disproportionally benefit pregnant women from this resource-limited population. Trial registration number NCT02797327.
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    A modular framework for the development of targeted Covid-19 blood transcript profiling panels
    (2020-07-31) Darawan Rinchai; Basirudeen Syed Ahamed Kabeer; Mohammed Toufiq; Zohreh Tatari-Calderone; Sara Deola; Tobias Brummaier; Mathieu Garand; Ricardo Branco; Nicole Baldwin; Mohamed Alfaki; Matthew C. Altman; Alberto Ballestrero; Matteo Bassetti; Gabriele Zoppoli; Andrea De Maria; Benjamin Tang; Davide Bedognetti; Damien Chaussabel; Ospedale Policlinico San Martino; Nepean Clinical School; Shoklo Malaria Research Unit; Benaroya Research Institute at Virginia Mason; Baylor Institute for Immunology Research; Università degli Studi di Genova; Universitat Basel; Swiss Tropical and Public Health Institute (Swiss TPH); University of Washington, Seattle; Nuffield Department of Medicine; Sidra Medicine
    BACKGROUND: Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of targeted blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. METHODS: We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. RESULTS: As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: immunological relevance, therapeutic development relevance and SARS biology relevance. CONCLUSION: Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients.
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    Shared and organism-specific host responses to childhood diarrheal diseases revealed by whole blood transcript profiling
    (2018-01-01) Hannah A. DeBerg; Mussaret B. Zaidi; Matthew C. Altman; Prasong Khaenam; Vivian H. Gersuk; Freddy D. Campos; Iza Perez-Martinez; Mario Meza-Segura; Damien Chaussabel; Jacques Banchereau; Teresa Estrada-Garcia; Peter S. Linsley; Michigan State University; Benaroya Research Institute at Virginia Mason; University of Washington School of Medicine; Centro de Investigacion y de Estudios Avanzados; Mahidol University; Hospital General O’Horan; Jackson Laboratory for Genomic Medicine
    © 2018 DeBerg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Globally, diarrheal diseases are a leading cause of death in children under five and disproportionately affect children in developing countries. Children who contract diarrheal diseases are rarely screened to identify the etiologic agent due to time and cost considerations associated with pathogen-specific screening and hence pathogen-directed therapy is uncommon. The development of biomarkers to rapidly identify underlying pathogens could improve treatment options and clinical outcomes in childhood diarrheal diseases. Here, we perform RNA sequencing on blood samples collected from children evaluated in an emergency room setting with diarrheal disease where the pathogen(s) present are known. We determine host response gene signatures specific to Salmonella, Shigella and rotavirus, but not E. coli, infections that distinguish them from each other and from healthy controls. Specifically, we observed differential expression of genes related to chemokine receptors or inflammasome signaling in Shigella cases, such as CCR3, CXCR8, and NLRC4, and interferon response genes, such as IFI44 and OASL, in rotavirus cases. Our findings add insight into the host peripheral immune response to these pathogens, and suggest strategies and limitations for the use host response transcript signatures for diagnosing the etiologic agent of childhood diarrheal diseases.
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    Transketolase and vitamin B1 influence on ROS-dependent neutrophil extracellular traps (NETs) formation
    (2019-01-01) Donporn Riyapa; Darawan Rinchai; Veerachat Muangsombut; Chayanin Wuttinontananchai; Mohammed Toufiq; Damien Chaussabel; Manabu Ato; Jenefer M. Blackwell; Sunee Korbsrisate; University of Cambridge; National Institute of Infectious Diseases; Mahidol University; Faculty of Medicine, Siriraj Hospital, Mahidol University; Telethon Kids Institute; Systems Biology and Immunology Department; Sidra Medicine
    © 2019 Riyapa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Neutrophil extracellular traps (NETs) are a recently identified, web-like, extracellular structure composed of decondensed nuclear DNA and associated antimicrobial granules. NETs are extruded into the extracellular environment via the reactive oxygen species (ROS)-dependent cell death pathway participating in inflammation and autoimmune diseases. Transketolase (TKT) is a thiamine pyrophosphate (vitamin B1)-dependent enzyme that links the pentose phosphate pathway with the glycolytic pathway by feeding excess sugar phosphates into the main carbohydrate metabolic pathways to generate biosynthetic reducing capacity in the form of NADPH as a substrate for ROS generation. In this work, TKT was selected as a lead candidate from 24 NET-associated proteins obtained by literature screening and knowledge gap assessment. Consequently, we determined whether TKT influenced NET formation in vitro. We firstly established that the release of ROS-dependent NETs was significantly decreased after purified human PMNs were pretreated with oxythiamine, a TKT inhibitor, and in a concentration dependent manner. As a cofactor for TKT reaction, we evaluated the release of NET formation either in vitamin B1 treatment or in combined use of oxythiamine and vitamin B1, and found that those treatments also exerted a significant suppressive effect on the amount of NET-DNA and ROS production. The regulation of TKT by oxythiamine and/ or vitamin B1 may therefore be associated with response to the modulation of NET formation by preventing generation of excessive NETs in inflammatory diseases.
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    Vaginal Microbiota and Cytokine Levels Predict Preterm Delivery in Asian Women
    (2021-03-04) Manoj Kumar; Selvasankar Murugesan; Parul Singh; Marwa Saadaoui; Duaa Ahmed Elhag; Annalisa Terranegra; Basirudeen Syed Ahamed Kabeer; Alexandra K. Marr; Tomoshige Kino; Tobias Brummaier; Rose McGready; François Nosten; Damien Chaussabel; Souhaila Al Khodor; Faculty of Tropical Medicine, Mahidol University; Sidra Medicine; Universitat Basel; Swiss Tropical and Public Health Institute (Swiss TPH); Nuffield Department of Medicine
    Preterm birth (PTB) is the most common cause of neonatal morbidity and mortality worldwide. Approximately half of PTBs is linked with microbial etiologies, including pathologic changes to the vaginal microbiota, which vary according to ethnicity. Globally more than 50% of PTBs occur in Asia, but studies of the vaginal microbiome and its association with pregnancy outcomes in Asian women are lacking. This study aimed to longitudinally analyzed the vaginal microbiome and cytokine environment of 18 Karen and Burman pregnant women who delivered preterm and 36 matched controls delivering at full term. Using 16S ribosomal RNA gene sequencing we identified a predictive vaginal microbiota signature for PTB that was detectable as early as the first trimester of pregnancy, characterized by higher levels of Prevotella buccalis, and lower levels of Lactobacillus crispatus and Finegoldia, accompanied by decreased levels of cytokines including IFNγ, IL-4, and TNFα. Differences in the vaginal microbial diversity and local vaginal immune environment were associated with greater risk of preterm birth. Our findings highlight new opportunities to predict PTB in Asian women in low-resource settings who are at highest risk of adverse outcomes from unexpected PTB, as well as in Burman/Karen ethnic minority groups in high-resource regions.