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Article ; Online: Finger stick blood collection for gene expression profiling and storage of tempus blood RNA tubes [version 2; referees

Darawan Rinchai / Esperanza Anguiano / Phuong Nguyen / Damien Chaussabel

F1000Research, Vol

1 approved, 2 approved with reservations]

2017 Volume 5

Abstract: With this report we aim to make available a standard operating procedure (SOP) developed for RNA stabilization of small blood volumes collected via a finger stick. The anticipation that this procedure may be improved through peer-review and/or readers ... ...

Abstract	With this report we aim to make available a standard operating procedure (SOP) developed for RNA stabilization of small blood volumes collected via a finger stick. The anticipation that this procedure may be improved through peer-review and/or readers public comments is another element motivating the publication of this SOP. Procuring blood samples from human subjects can, among other uses, enable assessment of the immune status of an individual subject via the profiling of RNA abundance using technologies such as real time PCR, NanoString, microarrays or RNA-sequencing. It is often desirable to minimize blood volumes and employ methods that are the least invasive and can be practically implemented outside of clinical settings. Finger stick blood samples are increasingly used for measurement of levels of pharmacological drugs and biological analytes. It is a simple and convenient procedure amenable for instance to field use or self-collection at home using a blood sample collection kit. Such methodologies should also enable the procurement of blood samples at high frequency for health or disease monitoring applications.
Keywords	Medical Genetics ; Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-03-01T00:00:00Z
Publisher	F1000 Research Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe

Gaspard Kerner / Anna-Lena Neehus / Quentin Philippot / Jonathan Bohlen / Darawan Rinchai / Nacim Kerrouche / Anne Puel / Shen-Ying Zhang / Stéphanie Boisson-Dupuis / Laurent Abel / Jean-Laurent Casanova / Etienne Patin / Guillaume Laval / Lluis Quintana-Murci

Cell Genomics, Vol 3, Iss 2, Pp 100248- (2023)

2023

Abstract: Summary: Ancient genomics can directly detect human genetic adaptation to environmental cues. However, it remains unclear how pathogens have exerted selective pressures on human genome diversity across different epochs and affected present-day ... ...

Abstract	Summary: Ancient genomics can directly detect human genetic adaptation to environmental cues. However, it remains unclear how pathogens have exerted selective pressures on human genome diversity across different epochs and affected present-day inflammatory disease risk. Here, we use an ancestry-aware approximate Bayesian computation framework to estimate the nature, strength, and time of onset of selection acting on 2,879 ancient and modern European genomes from the last 10,000 years. We found that the bulk of genetic adaptation occurred after the start of the Bronze Age, <4,500 years ago, and was enriched in genes relating to host-pathogen interactions. Furthermore, we detected directional selection acting on specific leukocytic lineages and experimentally demonstrated that the strongest negatively selected candidate variant in immunity genes, lipopolysaccharide-binding protein (LBP) D283G, is hypomorphic. Finally, our analyses suggest that the risk of inflammatory disorders has increased in post-Neolithic Europeans, possibly because of antagonistic pleiotropy following genetic adaptation to pathogens.
Keywords	ancient DNA ; immunity ; host defense ; natural selection ; local adaptation ; inflammatory disorders ; Genetics ; QH426-470 ; Internal medicine ; RC31-1245
Subject code	930
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A curated compendium of monocyte transcriptome datasets of relevance to human monocyte immunobiology research [version 2; referees

Darawan Rinchai / Sabri Boughorbel / Scott Presnell / Charlie Quinn / Damien Chaussabel

F1000Research, Vol

2 approved]

2016 Volume 5

Abstract: Systems-scale profiling approaches have become widely used in translational research settings. The resulting accumulation of large-scale datasets in public repositories represents a critical opportunity to promote insight and foster knowledge discovery. ... ...

Abstract	Systems-scale profiling approaches have become widely used in translational research settings. The resulting accumulation of large-scale datasets in public repositories represents a critical opportunity to promote insight and foster knowledge discovery. However, resources that can serve as an interface between biomedical researchers and such vast and heterogeneous dataset collections are needed in order to fulfill this potential. Recently, we have developed an interactive data browsing and visualization web application, the Gene Expression Browser (GXB). This tool can be used to overlay deep molecular phenotyping data with rich contextual information about analytes, samples and studies along with ancillary clinical or immunological profiling data. In this note, we describe a curated compendium of 93 public datasets generated in the context of human monocyte immunological studies, representing a total of 4,516 transcriptome profiles. Datasets were uploaded to an instance of GXB along with study description and sample annotations. Study samples were arranged in different groups. Ranked gene lists were generated based on relevant group comparisons. This resource is publicly available online at http://monocyte.gxbsidra.org/dm3/landing.gsp.
Keywords	Data Sharing ; Genomics ; Medicine ; R ; Science ; Q
Subject code	306
Language	English
Publishing date	2016-04-01T00:00:00Z
Publisher	F1000 Research Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Increased abundance of ADAM9 transcripts in the blood is associated with tissue damage [version 2; referees

Darawan Rinchai / Chidchamai Kewcharoenwong / Bianca Kessler / Ganjana Lertmemongkolchai / Damien Chaussabel

F1000Research, Vol

2 approved, 1 approved with reservations]

2016 Volume 4

Abstract: Background: Members of the ADAM (a disintegrin and metalloprotease domain) family have emerged as critical regulators of cell-cell signaling during development and homeostasis. ADAM9 is consistently overexpressed in various human cancers, and has been ... ...

Abstract	Background: Members of the ADAM (a disintegrin and metalloprotease domain) family have emerged as critical regulators of cell-cell signaling during development and homeostasis. ADAM9 is consistently overexpressed in various human cancers, and has been shown to play an important role in tumorigenesis. However, little is known about the involvement of ADAM9 during immune-mediated processes. Results: Mining of an extensive compendium of transcriptomic datasets identified important gaps in knowledge regarding the possible role of ADAM9 in immunological homeostasis and inflammation: 1) The abundance of ADAM9 transcripts in the blood was increased in patients with acute infection but, 2) changed very little after in vitro exposure to a wide range of pathogen-associated molecular patterns (PAMPs). 3) Furthermore it was found to increase significantly in subjects as a result of tissue injury or tissue remodeling, in absence of infectious processes. Conclusions: Our findings indicate that ADAM9 may constitute a valuable biomarker for the assessment of tissue damage, especially in clinical situations where other inflammatory markers are confounded by infectious processes.
Keywords	Genomics ; Structure: Transcription & Translation ; Medicine ; R ; Science ; Q
Language	English
Publishing date	2016-10-01T00:00:00Z
Publisher	F1000 Research Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Transketolase and vitamin B1 influence on ROS-dependent neutrophil extracellular traps (NETs) formation.

Donporn Riyapa / Darawan Rinchai / Veerachat Muangsombut / Chayanin Wuttinontananchai / Mohammed Toufiq / Damien Chaussabel / Manabu Ato / Jenefer M Blackwell / Sunee Korbsrisate

PLoS ONE, Vol 14, Iss 8, p e

2019 Volume 0221016

Abstract: 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 ... ...

Abstract	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.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Neutrophil-Driven Inflammatory Signature Characterizes the Blood Transcriptome Fingerprint of Psoriasis

Arun Rawat / Darawan Rinchai / Mohammed Toufiq / Alexandra K. Marr / Tomoshige Kino / Mathieu Garand / Zohreh Tatari-Calderone / Basirudeen Syed Ahamed Kabeer / Navaneethakrishnan Krishnamoorthy / Davide Bedognetti / Mohammed Yousuf Karim / Konduru S. Sastry / Damien Chaussabel

Frontiers in Immunology, Vol

2020 Volume 11

Abstract: Transcriptome profiling approaches have been widely used to investigate the mechanisms underlying psoriasis pathogenesis. Most researchers have measured changes in transcript abundance in skin biopsies; relatively few have examined transcriptome changes ... ...

Abstract	Transcriptome profiling approaches have been widely used to investigate the mechanisms underlying psoriasis pathogenesis. Most researchers have measured changes in transcript abundance in skin biopsies; relatively few have examined transcriptome changes in the blood. Although less relevant to the study of psoriasis pathogenesis, blood transcriptome profiles can be readily compared across various diseases. Here, we used a pre-established set of 382 transcriptional modules as a common framework to compare changes in blood transcript abundance in two independent public psoriasis datasets. We then compared the resulting “transcriptional fingerprints” to those obtained for a reference set of 16 pathological or physiological states. The perturbations in blood transcript abundance in psoriasis were relatively subtle compared to the changes we observed in other autoimmune and auto-inflammatory diseases. However, we did observe a consistent pattern of changes for a set of modules associated with neutrophil activation and inflammation; interestingly, this pattern resembled that observed in patients with Kawasaki disease. This similarity between the blood-transcriptome signatures in psoriasis and Kawasaki disease suggests that the immune mechanisms driving their pathogenesis might be partially shared.
Keywords	psoriasis ; transcriptomics ; blood ; Kawasaki disease ; systems biology ; Immunologic diseases. Allergy ; RC581-607
Subject code	610
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer

Claudia Winkler / Matthew King / Julie Berthe / Domenico Ferraioli / Anna Garuti / Federica Grillo / Jaime Rodriguez-Canales / Lorenzo Ferrando / Nicolas Chopin / Isabelle Ray-Coquard / Oona Delpuech / Darawan Rinchai / Davide Bedognetti / Alberto Ballestrero / Elisabetta Leo / Gabriele Zoppoli

JCI Insight, Vol 6, Iss

2021 Volume 18

Abstract: Large independent analyses on cancer cell lines followed by functional studies have identified Schlafen 11 (SLFN11), a putative helicase, as the strongest predictor of sensitivity to DNA-damaging agents (DDAs), including platinum. However, its role as a ... ...

Abstract	Large independent analyses on cancer cell lines followed by functional studies have identified Schlafen 11 (SLFN11), a putative helicase, as the strongest predictor of sensitivity to DNA-damaging agents (DDAs), including platinum. However, its role as a prognostic biomarker is undefined, partially due to the lack of validated methods to score SLFN11 in human tissues. Here, we implemented a pipeline to quantify SLFN11 in human cancer samples. By analyzing a cohort of high-grade serous ovarian carcinoma (HGSOC) specimens before platinum-based chemotherapy treatment, we show, for the first time to our knowledge, that SLFN11 density in both the neoplastic and microenvironmental components was independently associated with favorable outcome. We observed SLFN11 expression in both infiltrating innate and adaptive immune cells, and analyses in a second, independent, cohort revealed that SLFN11 was associated with immune activation in HGSOC. We found that platinum treatments activated immune-related pathways in ovarian cancer cells in an SLFN11-dependent manner, representative of tumor-immune transactivation. Moreover, SLFN11 expression was induced in activated, isolated immune cell subpopulations, hinting that SLFN11 in the immune compartment may be an indicator of immune transactivation. In summary, we propose SLFN11 is a dual biomarker capturing simultaneously interconnected immunological and cancer cell–intrinsic functional dispositions associated with sensitivity to DDA treatment.
Keywords	Cell biology ; Oncology ; Medicine ; R
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Integrated transcriptional‐phenotypic analysis captures systemic immunomodulation following antiangiogenic therapy in renal cell carcinoma patients

Darawan Rinchai / Elena Verzoni / Veronica Huber / Agata Cova / Paola Squarcina / Loris De Cecco / Filippo deBraud / Raffaele Ratta / Matteo Dugo / Luca Lalli / Viviana Vallacchi / Monica Rodolfo / Jessica Roelands / Chiara Castelli / Damien Chaussabel / Giuseppe Procopio / Davide Bedognetti / Licia Rivoltini

Clinical and Translational Medicine, Vol 11, Iss 6, Pp n/a-n/a (2021)

2021

Abstract: Abstract Background The combination of immune checkpoint blockade (ICB) with standard therapies is becoming a common approach for overcoming resistance to cancer immunotherapy in most human malignancies including metastatic renal cell carcinoma (mRCC). ... ...

Abstract	Abstract Background The combination of immune checkpoint blockade (ICB) with standard therapies is becoming a common approach for overcoming resistance to cancer immunotherapy in most human malignancies including metastatic renal cell carcinoma (mRCC). In this regard, insights into the immunomodulatory properties of antiangiogenic agents may help designing multidrug schedules based on specific immune synergisms. Methods We used orthogonal transcriptomic and phenotyping platforms combined with functional analytic pipelines to elucidate the immunomodulatory effect of the antiangiogenic agent pazopanib in mRCC patients. Nine patients were studied longitudinally over a period of 6 months. We also analyzed transcriptional data from The Cancer Genome Atlas (TCGA) RCC cohort (N = 571) to assess the prognostic implications of our findings. The effect of pazopanib was assessed in vitro on NK cells and T cells. Additionally, myeloid‐derived suppressor (MDSC)‐like cells were generated from CD14+ monocytes transfected with mimics of miRNAs associated with MDSC function in the presence or absence of pazopanib. Results Pazopanib administration caused a rapid and dramatic reshaping in terms of frequency and transcriptional activity of multiple blood immune cell subsets, with a downsizing of MDSC and regulatory T cells in favor of a strong enhancement in PD‐1 expressing cytotoxic T and Natural Killer effectors. These changes were paired with an increase of the expression of transcripts reflecting activation of immune‐effector functions. This immunomodulation was marked but transient, peaking at the third month of treatment. Moreover, the intratumoral expression level of a MDSC signature (MDSC INT) was strongly associated with poor prognosis in RCC patients. In vitro experiments indicate that the observed immunomodulation might be due to an inhibitory effect on MDSC‐mediated suppression, rather than a direct effect on NK and T cells. Conclusions The marked but transient nature of this immunomodulation, peaking at the third month ...
Keywords	antiangiogenics ; bioinformatics ; blood transcriptomic profile ; cancer biomarkers ; immunomonitoring ; immunosuppression ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Blood Interferon Signatures Putatively Link Lack of Protection Conferred by the RTS,S Recombinant Malaria Vaccine to an Antigen-specific IgE Response [version 2; referees

Darawan Rinchai / Scott Presnell / Marta Vidal / Sheetij Dutta / Virander Chauhan / David Cavanagh / Gemma Moncunill / Carlota Dobaño / Damien Chaussabel

F1000Research, Vol

2 approved]

2017 Volume 4

Abstract: Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular ... ...

Abstract	Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular repertoire approach to re-analyze a publically available microarray blood transcriptome dataset monitoring the response to malaria vaccination. We report the seminal identification of interferon signatures in the blood of subjects on days 1, 3 and 14 following administration of the third dose of the RTS,S recombinant malaria vaccine. These signatures at day 1 correlate with protection, and at days 3 and 14 to susceptibility to subsequent challenge of study subjects with live parasites. In addition we putatively link the decreased abundance of interferon-inducible transcripts observed at days 3 and 14 post-vaccination with the elicitation of an antigen-specific IgE response in a subset of vaccine recipients that failed to be protected by the RTS,S vaccine. Furthermore, profiling of antigen-specific levels of IgE in a Mozambican cohort of malaria-exposed children vaccinated with RTS,S identified an association between elevated baseline IgE levels and subsequent development of naturally acquired malaria infection during follow up. Taken together these findings warrant further investigation of the role of antigen-specific IgE in conferring susceptibility to malaria infection.
Keywords	Bioinformatics ; Global Health ; Tropical & Travel-Associated Diseases ; Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-07-01T00:00:00Z
Publisher	F1000 Research Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A proteasome inhibitor produced by Burkholderia pseudomallei modulates intracellular growth

Wagley, Sariqa / Darawan Rinchai / Ganjana Lertmemongkolchai / Gregory J. Bancroft / Laura Conejero / Muthita Vanaporn / Richard W. Titball

Elsevier Ltd Microbial pathogenesis. 2017 June, v. 107

2017

Abstract: The NRPS/PKS cluster encodes the enzymes necessary for glidobactin synthesis it is partially conserved in various members of the Burkholderia genus including B. pseudomallei. In this study we have shown that the insertional inactivation or deletion of ... ...

Abstract	The NRPS/PKS cluster encodes the enzymes necessary for glidobactin synthesis it is partially conserved in various members of the Burkholderia genus including B. pseudomallei. In this study we have shown that the insertional inactivation or deletion of glbC in this cluster in B. pseudomallei could reduce the ability of the bacterium to survive or grow in murine macrophages or in human neutrophils. Exogenously added proteasome inhibitors were able to chemically complement the mutation. The insertional inactivation or deletion of glbC increased virulence in an acute model of infection in Balb/c or C57BL/6 mice but virulence in a chronic model of infection was similar to that of the wild type. Our findings contrast with the previous finding that inactivation of the glb gene cluster in B. pseudomallei strain 1026b resulted in marked attenuation, and provides evidence of differential roles for some genes in virulence of different strains of B. pseudomallei.
Keywords	bacteria ; Burkholderia pseudomallei ; enzymes ; humans ; macrophages ; mice ; models ; multigene family ; mutation ; neutrophils ; proteasome inhibitors ; virulence
Language	English
Dates of publication	2017-06
Size	p. 175-180.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2017.03.015
Database	NAL-Catalogue (AGRICOLA)

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