Biology subjects

Le Bizec, B.

Publications and source records attributed to Le Bizec, B..

3 recordsLinked to original sources

bioRxiv2020

Combining mass spectrometric platforms for lipidome investigation - Application to the characterisation of disruptions in the lipid profile of pig serum upon β agonist treatment

In the last decade, many mass spectrometric fingerprinting methods dedicated to lipidomics have been proposed: either non-targeted approaches, coupled with annotation methods, or targeted strategies, aiming at specifically monitoring a limited number of substances. In a general public health perspective and through a strategy combining non-targeted and targeted lipidomics MS-based approaches, this study aims at identifying disrupted patterns in serum lipidome upon growth promoter treatment in pig and evaluating the relative contributions of the three platforms involved. Pig serum samples collected during an animal experiment involving control and treated animals, whose food had been supplemented with ractopamine, were extracted and characterised using three MS strategies: Non-targeted RP LC-HRMS; the targeted Lipidyzer platform (differential ion mobility associated with shotgun lipidomics) and a homemade LC-HRMS triglyceride platform. The three different platforms showed complementarity insight into lipid characterisation, which, applied to a selected set of samples, enabled highlighting specific lipid profile patterns involving various lipid classes, mainly in relation with cholesterol esters, sphingomyelins, lactosylceramide, phosphatidylcholines and triglycerides. Thanks to the combination of both non-targeted and targeted MS approaches, the exploration of various compartments of the pig serum lipidome could be performed, including commonly characterised lipids (Lipidyzer), triglyceride isomers (Triglyceride platform) -whose accurate analysis was considered an analytical challenge, and unique lipid features (non-targeted LC-HRMS). Thanks to their respective characteristics, the complementarity of the three tools could be demonstrated for public health purposes, with enhanced lipidome coverage, level of characterisation and applicability.

biochemistry↗

bioRxiv2019

WiPP: Workflow for improved Peak Picking for Gas Chromatography-Mass Spectrometry (GC-MS) data

Lack of reliable peak detection impedes automated analysis of large scale GC-MS metabolomics datasets. Performance and outcome of individual peak-picking algorithms can differ widely depending on both algorithmic approach and parameters as well as data acquisition method. Comparing and contrasting between algorithms is thus difficult. Here we present a workflow for improved peak picking (WiPP), a parameter optimising, multi-algorithm peak detection for GC-MS metabolomics. WiPP evaluates the quality of detected peaks using a machine learning-based classification scheme based on seven peak classes. The quality information returned by the classifier for each individual peak is merged with results from different peak detection algorithms to create one final high quality peak set for immediate down stream analysis. Medium and low quality peaks are kept for further inspection. By applying WiPP to standard compound mixes and a complex biological dataset we demonstrate that peak detection is improved through the novel way to assign peak quality, an automated parameter optimisation, and results integration across different embedded peak picking algorithms. Furthermore, our approach can provide an impartial performance comparison of different peak picking algorithms. WiPP is freely available on GitHub (https://github.com/bihealth/WiPP) under MIT licence.

bioinformatics↗

bioRxiv2018

Alternative (backdoor) androgen production and masculinization in the human fetus

Masculinization of the external genitalia in humans is dependent on formation of 5-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway. The fetal testes are essential for canonical androgen production but little is known about the synthesis of backdoor androgens despite their known critical role in masculinization. In this study, we have measured plasma and tissue levels of endogenous steroids in second trimester human male fetuses using multi-dimensional and high-resolution mass-spectrometry. Results show that androsterone is the principal backdoor androgen in the fetal circulation and that DHT is undetectable (<1ng/ml). Backdoor pathway intermediates are found primarily in the placenta and fetal liver with significant androsterone levels also in the fetal adrenal. Backdoor intermediates, including androsterone, are mostly undetectable in the fetal testes. This is consistent with transcript levels of enzymes involved in the backdoor pathway (SRD5A1, AKR1C2/4, CYP17A1), as measured by qPCR. These data identify androsterone as the predominant backdoor androgen in the human fetus and show that it is formed primarily in non-gonadal tissue with placental progesterone the likely substrate. Masculinization of the human fetus depends, therefore, on androgen synthesis by both the fetal testes and non-gonadal tissues leading to DHT formation at the genital tubercle. Our findings provide, for the first time, a solid basis to explain why placental insufficiency is associated with disorders of sex development in humans

physiology↗