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Bioinformatics for Precision Medicine in Oncology: principles and application to the SHIVA clinical trial

By Nicolas eServant, Nicolas eServant, Nicolas eServant, Julien eRoméjon, Julien eRoméjon, Julien eRoméjon, Pierre eGestraud, Pierre eGestraud, Pierre eGestraud, Philippe eLa Rosa, Philippe eLa Rosa, Philippe eLa Rosa, Georges eLucotte, Georges eLucotte, Georges eLucotte, Séverine eLair, Séverine eLair, Séverine eLair, Virginie eBernard, Bruno eZeitouni, Bruno eZeitouni, Bruno eZeitouni, Fanny eCoffin, Fanny eCoffin, Fanny eCoffin, Gérôme eJules-Clément, Gérôme eJules-Clément, Gérôme eJules-Clément, Gérôme eJules-Clément, Florent eYvon, Florent eYvon, Florent eYvon, Alban eLermine, Alban eLermine, Alban eLermine, Patrick ePoullet, Patrick ePoullet, Patrick ePoullet, Stéphane eLiva, Stéphane eLiva, Stéphane eLiva, Stuart ePook, Stuart ePook, Stuart ePook, Tatiana ePopova, Camille eBarette, Camille eBarette, Camille eBarette, Camille eBarette, François ePrud'homme, François ePrud'homme, François ePrud'homme, Jean-Gabriel eDick, Maud eKamal, Christophe eLe Tourneau, Christophe eLe Tourneau, Emmanuel eBarillot, Emmanuel eBarillot, Emmanuel eBarillot and Philippe eHupé and Philippe eHupé and Philippe eHupé and Philippe eHupé

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

Topics: bioinformatics, Sequencing, Clinical Trial, oncology, SHIVA, precision medicine, Genetics, QH426-470
Publisher: Frontiers Media S.A.
Year: 2014
DOI identifier: 10.3389/fgene.2014.00152
OAI identifier: oai:doaj.org/article:39bea5026b3849e0b2338d109ce7d0d3
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