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Biology subjects

Aubry, M.

Publications and source records attributed to Aubry, M..

9 recordsLinked to original sources

Refining type and timing of measured crop variables for the calibration of a new winter wheat cultivar in the STICS crop model

Crop models need to be regularly upgraded with parametrization for new cultivars but this requires calibration, which is a major challenge. With winter wheat cultivar Rubisko as a case study, we propose to apply a calibration protocol to estimate the parameters of this new cultivar with multi-trials experimental data. We tested the calibration protocol in different conditions including or not LAI and/or biomass experimental data and we found that the resulting LAI and biomass dynamics strongly diverge. Several key findings emerge from this study: (1) RUE parameters should be excluded from the calibration process, as their critical role in biomass dynamics causes the optimization algorithm to treat them as adjustment parameters, resulting in unrealistic values for multiple parameters; (2) either LAI or biomass variables alone are sufficient for calibration, enabling experimental efforts to focus on one variable rather than both; and (3) the use of a synthetic dataset has facilitated the identification of the optimal type and timing of data collection needed to parameterize a new variety in the model. Moreover, the proposed methodology offers extrapolatable solutions applicable to other contexts (e.g., different models or datasets) and provides guidance on acquiring the most effective dataset for optimal calibration. The unbalanced structure of our dataset also highlighted the need to mobilize other calibration criteria (weighted RMSE) and alternative solutions to bridge the gap between quantitative metrics and empirical visual assessments.

plant biology↗

A Genome-wide CRISPR screen unveils WDR91 protein as a promoter of productive ASO activity

Antisense oligonucleotides (ASOs) belong to promising therapeutics for the treatment of neurologic, muscular and metabolic disorders. Several ASOs have been approved so far and more than a hundred clinical trials are currently underway covering a dozen therapeutic areas. Yet, the mechanisms of internalization and cell trafficking of these molecules remain poorly understood. Moreover, with only a small fraction of ASOs reaching the correct cellular compartment following systemic delivery, the majority of targeted diseases requires recurrent injections of ASOs. A deeper understanding of these mechanisms would guide the improvement of their potency and thus, reduce the amount of delivered ASOs and their potential side-effects. Here, using a CRISPR screen, we investigated intracellular proteins involved in ASOs efficiency using a whole genome approach and identified several potential regulators which could significantly impact ASOs potency in melanoma cells. We validated WD Repeat Domain 91 (WDR91), a regulator of endosomal maturation, as a modulator whose depletion significantly inhibits ASO productive activity. This study provides the first list of ASO modulators using a biologically relevant assay to estimate the role of these proteins. In conclusion, these data could lead to a better understanding of the mechanisms favoring productive uptake or improved endosomal escape of ASOs.

molecular biology↗

Cirscan: a shiny application to identify differentially active sponge mechanisms and visualize circRNA-miRNA-mRNA networks.

BackgroundNon-coding RNAs represent a large part of the human transcriptome and have been shown to play an important role in disease such as cancer. However, their biological functions are still incompletely understood. Among noncoding RNAs, circular RNAs (circRNAs) have recently been identified for their microRNA (miRNA) sponge function which allows them to modulate the expression of miRNA target genes by taking on the role of competitive endogenous RNAs (ce-circRNAs). Today, most computational tools are not adapted to the search for ce-circRNAs or have not been developed for the search for ce-circRNAs from users transcriptomic data. ResultsIn this study, we present Cirscan (CIRcular RNA Sponge CANdidates), an interactive Shiny application that automatically infers circRNA-miRNA-mRNA networks from human multi-level transcript expression data from two biological conditions (e.g. tumor versus normal conditions in the case of cancer study) in order to identify on a large scale, potential sponge mechanisms active in a specific condition. Cirscan ranks each circRNA-miRNA-mRNA subnetwork according to a sponge score that integrates multiple criteria based on interaction reliability and expression level. Finally, the top ranked sponge mechanisms can be visualized as networks and an enrichment analysis is performed to help its biological interpretation. We showed on two real case studies that Cirscan is capable of retrieving sponge mechanisms previously described, as well as identifying potential novel circRNA sponge candidates. ConclusionsCirscan can be considered as a companion tool for biologists, facilitating their ability to prioritize sponge mechanisms for experimental validations and identifying potential therapeutic targets. Cirscan is implemented in R, released under the license GPL-3 and accessible on GitLab (https://gitlab.com/geobioinfo/cirscan_Rshiny). The scripts used in this paper are also provided on Gitlab (https://gitlab.com/geobioinfo/cirscan_paper).

bioinformatics↗

TGFβ-induced long non-coding RNA LINC00313 activates Wnt signaling and promotes cholangiocarcinoma

Cholangiocarcinoma (CCA) is a poor prognosis liver cancer characterized by high aggressiveness and resistance to therapy. Long non-coding RNAs (lncRNAs) and signals imposed by oncogenic pathways, such as transforming growth factor {beta} (TGF{beta}), contribute to cholangiocarcinogenesis. Here, we identified LINC00313 lncRNA as a novel target of TGF{beta} signalling in CCA cells. TGF{beta} induced LINC00313 expression in a T{beta}RI/Smad-dependent manner. Gene expression and genome-wide chromatin accessibility profiling revealed that nuclear LINC00313 transcriptionally regulated genes involved in Wnt signalling, such as TCF7. LINC00313 gain-of-function enhanced TCF/LEF-dependent transcription, promoted colony formation in vitro and accelerated tumour growth in vivo. Genes associated with LINC00313 over-expression in human CCA were characterized by KRAS and TP53 mutations and reduced patients overall survival. Mechanistically, actin-like 6A (ACTL6A), a subunit of SWI/SNF chromatin remodelling complex, interacted with LINC00313 and impacted on TCF7 and SULF2 transcription. We propose a model whereby TGF{beta} induces LINC00313 in order to regulate expression of hallmark Wnt pathway genes, in co-operation with SWI/SNF. By modulating key genes of the Wnt pathway, LINC00313 fine-tunes Wnt/TCF/LEF-dependent transcriptional responses and boosts cholangiocarcinogenesis.

cancer biology↗

Genomic characteristics and clinical significance of CD56+ Circulating Tumor Cells in Small Cell Lung Carcinoma

IntroductionCirculating Tumor Cells (CTC) have been studied in various solid tumors but clinical utility of CTC in Small Cell Lung Cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics. Patients and methodsCTC-CPC is a monocentric prospective non-interventional study including treatment-naive newly diagnosed SCLC. CD56+CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to Whole-exome-sequencing (WES). ResultsPhenotypic study confirms tumor lineage and tumorigenic properties of isolated cells for the 4 patients analyzed with WES. WES of CD56+CTC and matched tumor biopsy reveal genomic alteration frequently impaired in SCLC. At diagnosis CD56+CTC were characterized by a high mutation load, a distinct mutational profile and a unique genomic, compared to match tumors biopsies. In addition to classical pathways altered in SCLC, we found new biological processes specifically affected in CD56+CTC at diagnosis. High numeration of CD56+CTC (>7/ml) at diagnosis was associated with ES-SCLC. Comparing CD56+CTC isolated at diagnosis and relapse, we identify differentially altered oncogenic pathways (e.g. DLL3 or MAPK pathway). ConclusionsWe report a versatile method of CD56+CTC detection in SCLC. Numeration of CD56+CTC at diagnosis is correlated with disease extension. Isolated CD56+CTC are tumorigenic and a distinct mutational profile. We report a minimal gene set as a unique signature of CD56+CTC and identify new affected biological pathways enriched in EpCAM-independent isolated CTC in SCLC.

cancer biology↗

Uveal Melanoma: a miR-16 disease?

Uveal melanoma (UM), the most common primary intraocular tumor in adults, has been extensively characterized by omics technologies during the last 5 years. Despite the discovery of gene signatures, the molecular actors driving the cancer aggressiveness are not fully understood and UM is still associated to a dismal overall survival at metastatic stage. Here, we showed that microRNA-16 (miR-16) is involved in uveal melanoma by an unexpected mechanism. By defining the miR-16-interactome, we revealed that miR-16 mainly interacts via non-canonical base-pairing to a subset of RNAs, promoting their expression levels (sponge RNAs). Consequently, the canonical miR-16 activity, involved in the RNA decay of oncogenes such as cyclin D1 and D3, is impaired. This miR-16 non-canonical base-pairing to sponge RNAs can explain both the derepression of miR-16 targets and the promotion of oncogenes expression observed for patients with poor overall survival in two cohorts. miR-16 activity assessment using our sponge-signature discriminates the patients overall survival as efficiently as the current method based on copy number variations and driver mutations detection. To conclude, miRNA loss of function due to miRNA sequestration seems to promote cancer burden by two combined events - "loss of brake and an acceleration". Our results highlight the oncogenic role of the non-canonical base-pairing between miRNAs/mRNAs in uveal melanoma.

cancer biology↗

Engineering E. coli for magnetic control and the spatial localization of functions

The fast-developing field of synthetic biology enables broad applications of programmed microorganisms including the development of whole-cell biosensors, delivery vehicles for therapeutics, or diagnostic agents. However, the lack of spatial control required for localizing microbial functions could limit their use and induce their dilution leading to ineffective action or dissemination. To overcome this limitation, the integration of magnetic properties into living systems enables a contact-less and orthogonal method for spatiotemporal control. Here, we generated a magnetic-sensing Escherichia coli by driving the formation of iron-rich bodies into bacteria. We found that these bacteria could be spatially controlled by magnetic forces and sustained cell growth and division, by transmitting asymmetrically their magnetic properties to one daughter cell. We combined the spatial control of bacteria with genetically encoded-adhesion properties to achieve the magnetic capture of specific target bacteria as well as the spatial modulation of human cell invasions.

synthetic biology↗

Zika virus seroprevalence declines and neutralization antibodies wane in adults following outbreaks in French Polynesia and Fiji

BackgroundSerosurveys published following major outbreaks of Zika virus (ZIKV) have so far shown a high level of seroprevalence from samples collected within 12 months of the first confirmed case. A common assumption is that ZIKV infection confers long-term protection against reinfection, preventing ZIKV from re-emerging in previously affected areas for many years. However, the long-term immune response to ZIKV following an outbreak remains poorly documented.\n\nMethodsWe compared results from eight serological surveys, with sample sizes ranging from 49 to 700, before and after known ZIKV outbreaks in the Pacific region: five from cross-sectional studies of schoolchildren and the general population in French Polynesia over a seven-year period; and three from a longitudinal cohort in Fiji over a four-year period.\n\nFindingsWe found strong evidence of a decline in seroprevalence in both countries over a two-year period following first reported ZIKV transmission. In the cohort in Fiji, there was also a significant decline in antibody titres against ZIKV. However, the decline in seroprevalence was concentrated in adults, while high seroprevalence persisted in children.\n\nInterpretationThe observed patterns of long-term anti-ZIKV antibody levels following outbreaks in the Pacific could be an early indication of the dynamics of population immunity in Latin America. Given that ZIKV antibody levels can wane substantially over time, follow-up seroprevalence studies and prospective clinical trial designs in Latin America may need to be revised, and assumptions about the potential for ZIKV to re-emerge may need to be revisited.\n\nFundingPacific Funds, ANR, MRC, Wellcome, Royal Society.

epidemiology↗

Using paired serology and surveillance data to quantify dengue transmission and control during a large outbreak in Fiji

Dengue is a major health burden, but it can be challenging to examine transmission dynamics and evaluate control measures because outbreaks depend on multiple factors, including human population structure, prior immunity and climate. We combined population-representative paired sera collected before and after the major 2013/14 dengue-3 outbreak in Fiji with surveillance data to determine how such factors influence dengue virus transmission and control in island settings. Our results suggested the 10-19 year-old age group had the highest risk of acquiring infection, but we did not find strong evidence that other demographic or environmental risk factors were linked to seroconversion. Mathematical modelling showed that temperature-driven variation in transmission and herd immunity could not fully explain observed dynamics. However, there was evidence of an additional reduction in transmission coinciding with a vector clean-up campaign, which may have contributed to the decline in cases and prevented transmission continuing into the following season.

epidemiology↗