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27/03/2015

Bioinformatics, a Weapon to Fight Leukemia

Vidjil - © Bonsai - Inria

The Inria Lille - Nord Europe project-team Bonsai (run jointly with the CNRS and Université Lille1*) has created Vidjil, software for high-throughput analysis of white blood cells. Objective: provide physicians with a tool for treating leukemia. As March 28 and 29 are national leukemia days in France, the creators of Vidjil took this opportunity to explain how it works.

Vidjil is making giant strides. A research outcome of the Bonsai project-team, jointly run by Inria Lille - Nord Europe and CRIStAL (Centre de Recherche en Informatique, Signal et Automatique de Lille), this software is now used in one of the foremost genetic biology-pathology centers in France, at the Lille hospital . Since 2011, Bonsai has worked in close collaboration with the Lille CHRU hematology laboratory, directed by the Professor Claude Preudhomme. This lab monitors leukemia cases, a specialty representing around one third of its activities.

Bonsai members Mathieu Giraud and Mikaël Salson developed Vidjil. With others in the project-team, Marc Duez and Tatiana Rocher, they created this new tool in collaboration with the hospital teams. Vidjil's algorithms enable in-depth analysis of leukemia patients. Today, leukemia is still a hard-to-treat illness despite constant advances in research. The computational and processing capacities of this software offer physicians an invaluable way of refining their diagnoses.

Before, physicians could only look at the cancerous lymphocyte. Now they can access the entire population of lymphocytes

Vidjil provides a better picture of the development of acute leukemia, the form with the fastest progression, characterized by a sudden, abnormal proliferation of immature cancerous white blood cells. To be able to measure blood levels of these cells, whether they're antibody-forming B cells or immunity-boosting T cells, is crucial to determining the phase of the disease and initiating treatment. This is where Bonsai's software comes in. "The algorithmic part of Vidjil makes it possible to analyze a very high number of lymphocytes ", notes Mikaël Salson, a research-lecturer at Université Lille.

More specifically, Vidjil processesa million DNA sequences in a few minutes, which corresponds to a gigabyte of data. This means that physicians are no longer limited to analyzing the progression of a single lymphocyte (known as a "clone") that has been deemed cancerous and the cause of the leukemia. The implications are critical considering that relapse is possible in other lymphocytes than the analyzed cell at diagnosis. "Before, physicians could only look at the cancerous lymphocyte. Now they can access the entire population of lymphocytes ", notes Mathieu Giraud, a CNRS researcher. After analyzing the cells, Vidjil can separate the detected lymphocytes based on the genes used by their receptors and group them by type to facilitate study. PhD student Tatiana Rocher is working on a new algorithm that's even more efficient at analyzing these groups.

Detecting lymphocytes over the long term helps physicians and researchers better understand the disease, especially the issue of relapse.

Vidjil's high-throughput sequencing and the resulting analysis could also open the way to adapting treatment according to how the body responds.

Make results as clear as possible

As to Vidjil's online accessibility, the question remains an open one. Bonsai has worked on the visualization of Vidjil to make the results as clear as possible for hematologists. "The hematologist enters sequences in the software and can see the results ," explains Marc Duez, a SIRIC OncoLille engineer working on the project. The software presents a selection of analyzed lymphocytes in the form of curves. The hematologist can then follow the progression as he or she cares for the patient, measuring the effects of treatment on the lymphocyte population and detecting any relapse as rapidly as possible. "For physicians, this digital tool is revolutionary. That said, further improvements are necessary to fine-tune Vidjil visualization ," according to Mathieu Giraud and Mikaël Salson.

All patients in Nord - Pas de Calais and  Picardie with acute leukemia will have their analyses processed by Vidjil

At the same time, Bonsai is working to standardize medical protocols as part of a European consortium. "The consortium fully grasps the relevance of high-throughput sequencing. Every European patient should leave the lab with the same diagnosis, whether in Salamanca, Prague or Lille. " Vidjil is currently in a pre-production phase and used systematically at the Lille University Medical Center. "Since the first of January, all patients in Nord - Pas de Calais and  Picardie with acute leukemia have hadtheir analyses processed by Vidjil. This doesn't replace the usual monitoring, but just adds to it, since more time is needed to totally validate the protocols. In any case, we're very pleased because we have a chance to further test Vidjil, " the researchers note.Other French and European hospitals are currently testing Bonsai's software.

* UMR 9189 CNRS-Centrale Lille-Université Lille 1, CRIStAL.

Keywords: Medical Bonsai Algorithm Vidjil Bioinformatics Leukemia

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