title: Bioinformatics for precision medicine in oncology: principles and application to the SHIVA clinical trial.
abstract: Precision medicine (PM) requires the delivery of individually adapted medical care based on the genetic characteristics of each patient and his/her tumor. The last decade witnessed the development of high-throughput technologies such as microarrays and next-generation sequencing which paved the way to PM in the field of oncology. While the cost of these technologies decreases, we are facing an exponential increase in the amount of data produced. Our ability to use this information in daily practice relies strongly on the availability of an efficient bioinformatics system that assists in the translation of knowledge from the bench towards molecular targeting and diagnosis. Clinical trials and routine diagnoses constitute different approaches, both requiring a strong bioinformatics environment capable of (i) warranting the integration and the traceability of data, (ii) ensuring the correct processing and analyses of genomic data, and (iii) applying well-defined and reproducible procedures for workflow management and decision-making. To address the issues, a seamless information system was developed at Institut Curie which facilitates the data integration and tracks in real-time the processing of individual samples. Moreover, computational pipelines were developed to identify reliably genomic alterations and mutations from the molecular profiles of each patient. After a rigorous quality control, a meaningful report is delivered to the clinicians and biologists for the therapeutic decision. The complete bioinformatics environment and the key points of its implementation are presented in the context of the SHIVA clinical trial, a multicentric randomized phase II trial comparing targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer. The numerous challenges faced in practice during the setting up and the conduct of this trial are discussed as an illustration of PM application.
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Servant
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Julien
authors.initials: J
authors.lastname: Roméjon
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gestraud
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Philippe
authors.initials: P
authors.lastname: La Rosa
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Georges
authors.initials: G
authors.lastname: Lucotte
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Lair
authors.affiliation: INSERM U932, Paris France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Bernard
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Zeitouni
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Coffin
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France ; INSERM U932, Paris France.
authors.forename: Gérôme
authors.initials: G
authors.lastname: Jules-Clément
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Florent
authors.initials: F
authors.lastname: Yvon
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Alban
authors.initials: A
authors.lastname: Lermine
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Poullet
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Liva
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Stuart
authors.initials: S
authors.lastname: Pook
authors.affiliation: Institut Curie, Paris France ; INSERM U830, Paris France.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Popova
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France ; Institut Curie, Informatic Department, Paris France.
authors.forename: Camille
authors.initials: C
authors.lastname: Barette
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France ; Institut Curie, Informatic Department, Paris France ; Institut Curie, Sequencing Facility ICGex, Paris France.
authors.forename: François
authors.initials: F
authors.lastname: Prud'homme
authors.affiliation: Institut Curie, Informatic Department, Paris France.
authors.forename: Jean-Gabriel
authors.initials: JG
authors.lastname: Dick
authors.affiliation: Institut Curie, Translational Research Department, Paris France.
authors.forename: Maud
authors.initials: M
authors.lastname: Kamal
authors.affiliation: INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France ; Department of Medical Oncology, Institut Curie, Paris France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Le Tourneau
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.affiliation: Institut Curie, Paris France ; INSERM U900, Paris France ; Mines ParisTech, Fontainebleau France ; CNRS UMR144, Paris France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hupé
keywords: SHIVA; bioinformatics; clinical trial; oncology; precision medicine; sequencing