Biology subjects

Rey, G.

Publications and source records attributed to Rey, G..

6 recordsLinked to original sources

bioRxiv2022

Genetic variation in correlated regulatory region of Immunity

Studying the interplay between genetic variation, epigenetic changes and regulation of gene expression in immune cells is important to understand the modification of cellular states in various conditions, including immune diseases. Here, we built cis maps of regulatory regions with coordinated activity - Cis Regulatory Domains (CRDs) - in neutrophils, monocytes and T cells. For this, we leveraged (i) whole-genome sequencing (WGS), (ii) chromatin immunoprecipitation sequencing (ChIP-seq), (iii) DNA methylation (450k arrays), and (iv) transcriptional profiles (RNA-seq) from the BLUEPRINT consortium, for up to 200 individuals. Our study uncovers 9287, 7666 and 5480 histone CRDs (hCRDs) and 6053, 6112, 5701 methyl CRDs (mCRDs) in monocytes, neutrophils and T-cells, respectively. We discovered 15294 hCRD-gene and 6185 mCRD-gene associations (5% FDR). Only 33% of hCRD-gene associations and 37% of mCRD-gene associations were shared between cell-types, revealing the dynamic nature of regulatory interactions and how similarly located regulatory regions modulate the activity of different genes on different cell types. We mapped Quantitative Trait Loci associated with CRD activity (CRD-QTLs) and found that 89% and 70% of these hCRDs and mCRDs are under genetic control highlighting the importance of genetic variation to study the coordination of cellular regulatory programs. We found CRD-QTLs to be enriched in celltype-specific transcription factor binding sites, such as SPI1, STAT3, RFX1, SOX4, ATF3 for neutrophils and monocytes and TCF4 and BCL11A for T-cells, in line with the Human protein Atlas. We integrated PCHi-C data, which showed that most significant associations discovered within gene-CRD associations and co-expressed genes associated with the same CRD, involving large genomic distances, tend to happen between genomic regions in close spatial proximity. Finally, we mapped trans regulatory associations between CRDs, which enabled the discovery of 207 trans-eQTLs across cell types. Overlapping our hits with trans eQTLs from eQTLGen Consortium meta-analysis in whole blood revealed 52 trans-eQTLs shared between the two studies. Overall, we show that mapping functional regulatory units using population genomics data allows discovering important mechanisms in the regulation of gene expression in immune cells and gain a greater understanding of cell-type specific regulatory mechanisms of immunity.

bioinformatics↗

bioRxiv2021

Functional dynamics of brain networks associated with carry-over effects of negative events on subsequent resting state.

Affective inertia represents the lasting impact of transient emotions at one time point on affective state at a subsequent time point. Here we describe the neural underpinnings of inertia following negative emotions elicited by sad events in movies. Using a co-activation pattern analysis of dynamic functional connectivity, we examined the temporal expression and reciprocal interactions among brain-wide networks during movies and subsequent resting periods. Our findings revealed distinctive spatiotemporal expression of visual (VIS), default mode (DMN), central executive (CEN), and frontoparietal control (FPCN) networks both in negative movies and in rest periods following these movies. We also identified different reciprocal relationships among these networks, in transitions from movie to rest. While FPCN and DMN expression increased during and after negative movies, respectively, FPCN occurrences during the movie predicted lower DMN and higher CEN expression during subsequent rest after neutral movies, but this relationship was reversed after the elicitation of negative emotions. Changes in FPCN and DMN activity correlated with more negative subjective affect. These findings provide new insights into the transient interactions of intrinsic brain networks underpinning the inertia of negative emotions. More specifically, they describe a major role of FPCN in emotion elicitation processes, with prolonged impact on DMN activity in subsequent rest, presumably involved in emotion regulation and restoration of homeostatic balance after negative events. HighlightsO_LIModulations of dynamic functional brain connectivity are associated to the temporal inertia of negative emotions. C_LIO_LIFunctional co-activations patterns (CAPs) during emotional episodes predict changes in spontaneous brain dynamics during subsequent resting state. C_LIO_LIClassical "task-rest" anticorrelations in network activity are reversed by negative emotions. C_LI

neuroscience↗

bioRxiv2020

The adaptive transcriptional response of pathogenic Leptospira to peroxide reveals new defenses against infection-related oxidative stress

Pathogenic Leptospira spp. are the causative agents of the waterborne zoonotic disease leptospirosis. During infection, Leptospira are confronted with dramatic adverse environmental changes such as deadly reactive oxygen species (ROS). Withstanding ROS produced by the host innate immunity is an important strategy evolved by pathogenic Leptospira for persisting in and colonizing hosts. In L. interrogans, genes encoding defenses against ROS are repressed by the peroxide stress regulator, PerR. In this study, RNA sequencing was performed to characterize both the L. interrogans adaptive response to low and high concentrations of hydrogen peroxide and the PerR regulon. We showed that Leptospira solicit three main peroxidase machineries (catalase, cytochrome C peroxidase and peroxiredoxin) and heme to detoxify oxidants produced during a peroxide stress. In addition, canonical molecular chaperones of the heat shock response and DNA repair proteins from the SOS response were required for Leptospira recovering from oxidative damages. Determining the PerR regulon allowed to identify the PerR-dependent mechanisms of the peroxide adaptive response and has revealed a PerR-independent regulatory network involving other transcriptional regulators, two-component systems and sigma factors as well as non-coding RNAs that putatively orchestrate, in concert with PerR, this adaptive response. In addition, we have identified other PerR-regulated genes encoding a TonB-dependent transport system, a lipoprotein (LipL48) and a two-component system (VicKR) involved in Leptospira tolerance to superoxide and that could represent the first defense mechanism against superoxide in L. interrogans, a bacterium lacking canonical superoxide dismutase. Our findings provide a comprehensive insight into the mechanisms required by pathogenic Leptospira to overcome infection-related oxidants during the arm race with a host. This will participate in framing future hypothesis-driven studies to identify and decipher novel virulence mechanisms in this life-threatening pathogen. Author summaryLeptospirosis is a zoonotic infectious disease responsible for over one million of severe cases and 60 000 fatalities annually worldwide. This neglected and emerging disease has a worldwide distribution, but it mostly affects populations from developing countries in sub-tropical areas. The causative agents of leptospirosis are pathogenic bacterial Leptospira spp. There is a considerable deficit in our knowledge of these atypical bacteria, including their virulence mechanisms. During infection, Leptospira are confronted with the deadly oxidants produced by the host tissues and immune response. Here, we have identified the cellular factors necessary for Leptospira to overcome the oxidative stress response. We found that Leptospira solicit peroxidases to detoxify oxidants as well as chaperones of the heat shock response and DNA repair proteins of the SOS response to recover from oxidative damage. Moreover, our study indicates that adaptation to oxidative stress is orchestrated by a regulatory network involving PerR and other transcriptional regulators, sigma factors, two component systems, and putative non-coding RNAs. These findings provide a comprehensive insight into the mechanisms required by pathogenic Leptospira to tolerate infection-related oxidants, helping identify novel virulence factors, developing new therapeutic targets and vaccines against leptospirosis.

microbiology↗

bioRxiv2019

Brain functional connectivity dynamics in the aftermaths of affective and cognitive events.

Neuroimaging studies have shown carry-over effects on brain activity and connectivity following both emotional and cognitive events, persisting even during subsequent rest. Here, we investigate the functional dynamics of such effects by identifying recurring co-activation patterns (CAPs). Using the precuneus as seed region, we compare carrying-over effects on brain-wide CAPs and their modulation after both affective and cognitive challenges. Female volunteers (n=19) underwent fMRI scanning during emotional induction with sad movie clips, and executive control tasks, each followed by resting periods. Several CAPs, overlapping the default mode, salience, attention, and social cognition networks were impacted by both the preceding events (movie or task) and their valence (neutral or negative), with differential fluctuations over time. Specifically, a modulation of CAPs in posterior cingulate and ventromedial prefrontal cortex was observed after exposure to negatively valenced emotional content and predicted changes in subjective affect. Additionally, CAPs in anterior cingulate cortex and dorsal fronto-parietal areas were induced by cognitive control in a negative, but not neutral context, and amplified by the task difficulty. These findings provide new insights on the anatomical organization and temporal inertia of intrinsic functional brain networks, engaged by transient emotions and presumably involved in subsequent adaptive homeostatic processes.

neuroscience↗

bioRxiv2018

Exploration Of The Timeliness Of ICD Codes In Administrative Databases: A Nationwide Study

INTRODUCTIONThe ICD codes are ubiquitously available in hospital information systems and have been used in a number of areas such as epidemiology, phenotype-genotype association mining, surveillance of the use of drugs and medical devices and health care evaluation. We aimed to analyze the timeliness of the 3-character ICD-10 codes collected in the French national hospital discharge summary database between 2008 and 2017 and we classified the codes according to their evolution.\n\nMATERIAL AND METHODSWe extracted all 3-character ICD-10 codes from all French hospital discharge summaries between 2008 and 2017. For each code and by the month, we computed a relative frequency; we also computed the overall amplitude of the study period. Temporal clustering, according to the SAX representation, was performed to classify the main evolution patterns.\n\nRESULTSWe extracted 238,334,751 encounters corresponding to 56,621,773 distinct patients. 1,006 ICD codes presented a variation of the relative amplitude of frequencies lower than 50%, 510 codes between 50% and 100% and 521 greater than 100%. Out of the 2,037 codes included in the study, we kept the 1,758 for the temporal clustering. Four clusters were identified, including a global increase and a global decrease patterns.\n\nDISCUSSIONThe overall results showed a strong instability (i.e. large variation of frequency over time) of the use of ICD codes over time, with an important variation of the relative amplitude of the frequencies. We distinguished between external factors due to changes in billing, organization, policy or regulation and intrinsic factors due to epidemiological phenomenon. The detailed analysis of profiles show that the same cluster can contain profiles influenced by intrinsic epidemiological or external factors or both. Additional knowledge and sources are probably required to determine automatically the origin of the profile.

epidemiology↗

bioRxiv2017

Non-canonical circadian oscillations in Drosophila S2 cells drive gene-expression cycles coupled to metabolic oscillations

Circadian rhythms are cell-autonomous biological oscillations with a period of about 24 hours. Current models propose that transcriptional feedback loops are the principal mechanism for the generation of circadian oscillations. In these models, Drosophila S2 cells are generally regarded as non-rhythmic cells, as they do not express several canonical circadian components. Using an unbiased multi-omics approach, we made the surprising discovery that Drosophila S2 cells do in fact display widespread daily rhythms. Transcriptomics and proteomics analyses revealed that hundreds of genes and their products are rhythmically expressed in a 24-hour cycle. Metabolomics analyses extended these findings and illustrated that central carbon metabolism and amino acid metabolism are the main pathways regulated in a rhythmic fashion. We thus demonstrate that daily genome-wide oscillations, coupled to metabolic cycles, take place in eukaryotic cells without the contribution of known circadian regulators.

systems biology↗