CE45 - Mathématique, informatique, automatique, traitement du signal pour répondre aux défis de la biologie et de la santé

SoftwAiR: High-throughput processing of real-time and high-resolution mass spectrometry analysis from exhaled air for the characterization of the human volatolome variations in disease and response to pharmacological treatments – SoftwAiR

Submission summary

SoftwAiR: High-throughput processing of real-time and high-resolution mass spectrometry analysis from exhaled air for the characterization of the human volatolome variations in disease and response to pharmacological treatments

Metabolomics is the last-born “omic” approach, consisting in exploring the metabolome; i.e. the expression of all endogenous molecules located downstream (in biological terms) of those targeted by established genomic, transcriptomic and proteomic methods. In the last years, an innovative metabolomic approach focusing on exhaled breath (and therefore called “breathomics” or “volatolomics”) has emerged. It consists in a comprehensive analysis of metabolism-derived Volatile Organic Compounds (VOCs) (the volatolome) in patients' exhaled air. Those VOCs can be directly derived from pulmonary metabolism and reflect the metabolic state of the lungs, but they can also be derived from all other organs by being transported through the bloodstream to the lungs and then into the exhaled air. Recent reports suggest that volatolomics is a promising tool for personalized medicine with major advantages over classical biological investigations: the sampling is completely non-invasive, painless and fast and some instruments allow real-time analysis. Such instruments, such as proton transfer reaction-high resolution mass spectrometry (PTR-HRMS) have emerged as a powerful technology for VOC analysis in a wide range of environmental, biological and medical applications. However, several pitfalls remain to be addressed before volatolomics can be adopted in routine medical practice, the major ones being the lack of bioinformatics tools for the efficient processing and analysis of real-time PTR-MS data and of the associated statistical pipelines for biomarker discovery. Here we have built a team of experienced clinicians, biologists, and applied mathematicians to propose for the first time 1) to develop innovative algorithms and software environment for the processing of real-time analysis of VOCs in exhaled air and to implement a statistical framework for the longitudinal study of individuals’ temporal profiles, and 2) to apply this workflow to samples obtained during a clinical trial aimed at identifying biomarkers of acute rejection in lung transplant recipients. The work will be carried out with data obtained from a last-generation, high-resolution and high-sensitivity PTR-time-of-flight instrument, equipped with a CE-labelled BET-med device to collect patient’s samples. The 3-year program of a PhD student, supervised by an internationally recognized expert in metabolomic data processing and analysis from the Commissariat à l’Energie Atomique (CEA) will mainly include i) the development of the bioinformatic tools for the processing of PTR-HRMS data (peak detection and quantification, peak alignment…), ii) the development of statistical workflows for biomarker discovery and longitudinal analysis and iii) the application of the developed tools to samples obtained in clinical trials taking place at Foch Hospital, starting with a study to detect acute rejection in lung transplant recipients. The completion of this study would result in real progresses in the medical management of patients, by avoiding numbers of invasive and time-consuming diagnostic methods, improving both quality, acceptability and the medico-economic burden of medical care. The dissemination of our results and tools in publicly available repositories and online platforms will enable the use of our approaches by other teams working in the field and also in non-medical applications worldwide. Moreover, prospects do exist in several other lung and non-lung diseases for which several clinical trials are already planed for the next months (detection of fungi or mycobacteria infections in immunocompromised or cystic fibrosis patients, monitoring of the response to targeted immunotherapies in patients with asthma...).

Project coordination

Etienne THEVENOT (Commissariat à l'Energie Atomique et aux Energies Alternatives - Laboratoire Analyse de Données et Intelligence des Systèmes)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

2IC Infection et Inflammation chronique
CEA - LIST Commissariat à l'Energie Atomique et aux Energies Alternatives - Laboratoire Analyse de Données et Intelligence des Systèmes
ASSOCIATION HOPITAL FOCH

Help of the ANR 192,966 euros
Beginning and duration of the scientific project: November 2018 - 36 Months

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