Niveau de diplôme exigé : Bac + 5 ou équivalent
Fonction : Doctorant
A propos du centre ou de la direction fonctionnelle
The Inria Université Côte d’Azur center counts 36 research teams as well as 7 support departments. The center's staff (about 500 people including 320 Inria employees) is made up of scientists of different nationalities (250 foreigners of 50 nationalities), engineers, technicians and administrative staff. 1/3 of the staff are civil servants, the others are contractual agents. The majority of the center’s research teams are located in Sophia Antipolis and Nice in the Alpes-Maritimes. Four teams are based in Montpellier and two teams are hosted in Bologna in Italy and Athens. The Center is a founding member of Université Côte d'Azur and partner of the I-site MUSE supported by the University of Montpellier.
Contexte et atouts du poste
The PhD position will take place within the framework of an interdisciplinary call between the immuno-oncology and Laënnec (artificial intelligernce for health) Marseille institutes.
The position will be located in the Inria-Inserm team COMPO (COMputational Pharmacology in Oncology), located in the University Hospital of Marseille (AP-HM). The team is composed of mathematicians, pharmacists and clinicians and is a unique multidisciplinary environment focused on developing novel computational tools for decision- making in clinical oncology.
The project will consist in working within the SChISM (Size Cfdna Immunotherapies Signature Monitoring) clinical study, in collaboration with AP-HM and the id-Solution and ADELIS biotechs. The PhD student will be co-supervised by a mathematician (Dr S. Benzekry) and a clinical oncologist (Pr S. Salas).
Mission confiée
Early prediction of resistance to immunotherapy is a major challenge in oncology. The ongoing SChISM clinical study proposes an innovative approach based on patented cfDNA (circulating free DNA) quantification methods. Leveraging the longitudinal and quantitative aspect of this data (260 patients in total), we propose to develop mechanistic models of cfDNA joint kinetics with other longitudinal markers and tumor size imaging. Such models embedded within a statistical mixed-effects framework will be calibrated to the population data and subsequently provide individual parameters using Bayesian estimation. Subsequently, we aim to develop integrative machine learning models able to predict outcome (response, PFS and OS) from the combination of these dynamic parameters and other variables available at baseline.
For a better knowledge of the proposed research subject :
[1] Claret, L. et al. A Model of Overall Survival Predicts Treatment Outcomes with Atezolizumab versus Chemotherapy in Non-Small Cell Lung Cancer Based on Early Tumor Kinetics. Clin Cancer Res, 24, 3292–3298 (2018).
[2] Khan, K. H. et al. Longitudinal Liquid Biopsy and Mathematical Modeling of Clonal Evolution Forecast Time to Treatment Failure in the PROSPECT-C Phase II Colorectal Cancer Clinical Trial. Cancer discovery (2018) doi:10.1158/2159-8290.cd-17-0891.
[3] Benzekry, S. Artificial intelligence and mechanistic modeling for clinical decision making in oncology. Clinical pharmacology and therapeutics (2020)
Principales activités
The objectives are to:
1) Establish and validate a mechanistic model of the joint kinetics of cfDNA concentrations and other circulating markers
2) Establish and validate a mixed-effects statistical model for quantification of inter-individual variability
3) Integrate the kinetic parameters together with baseline variables into ML pipelines for early prediction of outcome (response, progression-free survival, 3-years survival, overall survival)
keywords: immunotherapy, cfDNA, mechanistic modeling, machine learning, mixed-effects modeling
Examples of activities:
- Data exploration and visualization
- Biostatistics (e.g. statistical tests, survival analysis)
- Programming (R/python)
- Mathematical modeling of the pharmaco-physio-pathology
- Mixed-effects statistical modeling
- Literature review
- Analyze the requirements of the project partners
- Write synthetic and meaningful reports and scientific publications
Compétences
Technical skills and level required :
- Excellent data science programming skills (python/R)
- Familiarity with real-world data analysis
- Ideally, experience in mixed-effects modeling
Relational skills :
- Ability to work as a team
Avantages
- Subsidized meals
- Partial reimbursement of public transport costs
- Leave: 7 weeks of annual leave + 10 extra days off due to RTT (statutory reduction in working hours) + possibility of exceptional leave (sick children, moving home, etc.)
- Possibility of teleworking (after 6 months of employment) and flexible organization of working hours
- Professional equipment available (videoconferencing, loan of computer equipment, etc.)
- Social, cultural and sports events and activities
- Access to vocational training
- Social security coverage
Rémunération
1982€brut per month (year 1 & 2) and 2085€ brut/month (year 3)
Partager
Informations générales
- Thème/Domaine :
Neurosciences et médecine numériques
Statistiques (Big data) (BAP E) - Ville : Marseille
- Centre Inria : CRI Sophia Antipolis - Méditerranée
- Date de prise de fonction souhaitée : 2022-10-01
- Durée de contrat : 3 ans
- Date limite pour postuler : 2022-06-30
Contacts
- Equipe Inria : COMPO
-
Directeur de thèse :
Benzekry Sebastien / Sebastien.Benzekry@inria.fr
L'essentiel pour réussir
Strong motivation to apply computational methods to concrete health problems
A propos d'Inria
Inria est l’institut national de recherche dédié aux sciences et technologies du numérique. Il emploie 2600 personnes. Ses 200 équipes-projets agiles, en général communes avec des partenaires académiques, impliquent plus de 3500 scientifiques pour relever les défis du numérique, souvent à l’interface d’autres disciplines. L’institut fait appel à de nombreux talents dans plus d’une quarantaine de métiers différents. 900 personnels d’appui à la recherche et à l’innovation contribuent à faire émerger et grandir des projets scientifiques ou entrepreneuriaux qui impactent le monde. Inria travaille avec de nombreuses entreprises et a accompagné la création de plus de 180 start-up. L'institut s'efforce ainsi de répondre aux enjeux de la transformation numérique de la science, de la société et de l'économie.
Consignes pour postuler
Sécurité défense :
Ce poste est susceptible d’être affecté dans une zone à régime restrictif (ZRR), telle que définie dans le décret n°2011-1425 relatif à la protection du potentiel scientifique et technique de la nation (PPST). L’autorisation d’accès à une zone est délivrée par le chef d’établissement, après avis ministériel favorable, tel que défini dans l’arrêté du 03 juillet 2012, relatif à la PPST. Un avis ministériel défavorable pour un poste affecté dans une ZRR aurait pour conséquence l’annulation du recrutement.
Politique de recrutement :
Dans le cadre de sa politique diversité, tous les postes Inria sont accessibles aux personnes en situation de handicap.
Attention: Les candidatures doivent être déposées en ligne sur le site Inria. Le traitement des candidatures adressées par d'autres canaux n'est pas garanti.