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Conference presentations


API 2017 (Asociacion Panamericana de Infectologia) - XVIII Congresso Panamericano de Infectologia, 17-20 May 2017, Panama

“P8: Comorbidities increase In-Hospital Mortality in Dengue Patients in Mexico”, TOH M.L.[1], BAURIN N.[1], MORLEY D.[2], RECAMIER V.[2], GUERGOVA-KURAS M.[2], PUENTES-ROSAS E[3], OCHIAI L.[4], COUDEVILLE L.[1], MASCAREÑAS C.[3]
[1]Sanofi Pasteur, France; [2]Ariana Pharma, France; [3]Sanofi Pasteur, Mexico; [4]Sanofi Pasteur, Singapore

“P9: Comorbidities increase In-Hospital Mortality in Dengue Patients in Brazil”, TOH M.L.[1], BAURIN N.[1], MORLEY D.[2], RECAMIER V.[2], GUERGOVA-KURAS M.[2], PUENTES-ROSAS E[3], OCHIAI L.[4], COUDEVILLE L.[1], MASCAREÑAS C.[3]
[1]Sanofi Pasteur, France; [2]Ariana Pharma, France; [3]Sanofi Pasteur, Mexico; [4]Sanofi Pasteur, Singapore

Links: API 2017 conference website | Download P8 PDF | Download P9 PDF

TAT 2017: 15th International Congress on Targeted Anticancer Therapies, 6-8 Mar 2017, Paris, France

“O10.6 Initial perspectives from WINTHER, an international precision medicine trial using both DNA and RNA data to guide treatment”, Vladimir Lazar [1], Razelle Kurzrock [2], Raanan Berger [3], Jordi Rodon [4], Wilson Miller [5], Vincent Miller [6], Fanny Wunder [1], Eitan Rubin [7], Serge Koscielny [8], Mohammad Afshar [9], Jean-Charles Soria [8]
[1] Worldwide Innovative Networking (WIN) Consortium, Villejuif, France [2] UC San Diego Moores Cancer Center, San Diego, USA [3] Chaim Sheba Medical Center, Tel-Hashomer, Israel [4] Vall d’Hebron Institute of Oncology Universidad Autonoma de Barcelona, Barcelona, Spain [5] Segal Cancer Centre at the Jewish General Hospital, Montreal, Canada [6] Foundation Medicine Inc., Cambridge, USA [7] Ben-Gurion University of the Negev, Be’er Sheva, Israel [8] Gustave Roussy, Villejuif, France [9] Ariana Pharma, Paris, France

tat2017_thumbThe WINTHER clinical trial is a cutting edge precision medicine prospective study, using not only genomic but also transcriptomic assays to guide treatment decisions. This multinational trial (4 countries) coordinated by the Worldwide Innovative Networking (WIN) Consortium is structured in two arms. Arm A uses Foundation Medicine’s Foundation One DNA gene panel to guide therapeutic decisions. If no actionable alterations are identified or therapies suggested in Arm A are not available, patients are moved to the Arm B that uses an innovative transcriptomic assay and algorithm further developed in a clinical decision support system (Onco KEM). The study has included a broad range of solid tumor patients heavily pretreated that exhausted conventional therapy. The main study endpoint is the comparison of the progression-free-survival (PFS) under the WINTHER selected therapy to the PFS of the last therapeutic line for which the patient had a progression. 303 patients were registered in the study. 107 patients were treated according to the WINTHER therapeutic decisions taken by the study’s Clinical Management Committees. Analysis of the treated patients shows that 64% (69) were treated using the identified DNA based panel alterations. The transcriptomic test enabled treatment selection for the remaining 36% (38). This group consisted of 22% (23) patients for whom an actionable DNA alteration was not identified and an additional 14% (15) patients for whom the DNA based suggested therapy was not accessible in the clinical center. Indeed, Arm B assay explores a large number of genes (7442) and therapies (178) both targeted and chemotherapies. In 45% of patients in Arm A and 45% in Arm B, best response was Stable Disease or better based on already available data. While awaiting the final prospective efficacy data, the study already demonstrates that the innovative transcriptomic based decision support system fills a gap left by traditional DNA based targeted therapy, enabling more patients to reach a larger pool of accessible drugs and potentially benefit from precision medicine, even at a late stage of the disease, when no more clinical guidelines exist.

Links: Download abstracts PDF | Conference website

Institut Pasteur International Network Scientific Symposium, 29 Nov-2 Dec 2016, Paris, France

“117 – Combination Therapy in Melanoma: finding biomarkers of synergistic associations using Large Scale Drug Combination Screening and integrated Omics Data Analysis”, F. Parmentier [1], A. Amzallag [2], M. Guergova-Kuras [1], M. Afshar [1], C.H. Benes [2]
[1] Ariana Pharmaceuticals, Paris, France [2] Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA

poster117_thumbThe drive towards precision medicine in oncology is fueling the identification and characterization of an ever-increasing number of drugs specifically targeted to altered tumor targets. The lack of complete response and the emergence of resistance in large number of patients is pushing clinicians to search for combination therapies to prevent disease progression. The ability to perform large scale omic analysis against a large number of drugs is an opportunity to develop a systematic approach for identifying optimal drug combinations for a given patient. High throughput unbiased screening of targeted drug combinations, with appropriate library selection and mechanistic follow-up, can yield to clinically actionable combination therapeutic options. In this work, we screened a library of 24 melanoma cell lines against the 5778 pair combinations of 108 anticancer drugs. The synergistic effect across cell lines was assessed for each drug pair. The cell lines were characterized using 6916 omics features, including gene expression, copy number variations and single nucleotide polymorphism. Using a machine learning approach (KEM®) we systematically extracted all logical associations between omics features and drug pair synergies. Exploring a search space of around 150 million possible relations, we constructed a knowledge base by extracting 889 181 rules of interest for 4832 drug pairs. The knowledge base enables the exhaustive identification of specific markers linked to each synergistic pair. Detailed analysis of the combination of 104 drugs with PLX4720, a precursor of vemurafenib, a wellknown BRAFV600E inhibitor widely used in melanoma treatment, is presented showing specific markers that can gate the selection of a particular drug combination. We speculate that the identification of specific biomarkers linked to specific synergies may be transformed in the future into a therapeutic decision support system, identifying optimal combination therapies for melanoma patients.

Links: Download P117 PDF

ASTMH 2016: 65th Annual Meeting of the American Society of Tropical Medicine and Hygiene, 13-17 Nov 2016, Atlanta, USA

“212 – Management of dengue hospitalizations in Brazil during and outside epidemic periods: Insights from Data Mining”, Nicolas Baurin, David Morley, Leon Ochiai, Mariana Guergova-Kuras, Mohammad Afshar, Laurent Coudeville

Links: P212 abstract | Download P212 PDF | ASTMH 2016 conference website

EACR-23: 23rd Biennial Congress of the European Association for Cancer Research. From Basic Research to Personalised Cancer Treatment, 5-8 July 2014, Munich, Germany

“P667: Shorter multimarker signatures: a new tool to facilitate cancer diagnosis”, M.P. Schneider, N. Jullian, M. Afshar, M. Guergova-Kuras, Ariana Pharma.

Links: EACR-23 conference website | Download P667 PDF

WIN 2014: Breakthrough biomarker investigations and combined therapeutic approaches for precision cancer medicine, 23-24 June 2014, Paris, France

“P2.26: Computational biomarker models to predict response to lung cancer treatments from combined molecular data”, Marine Le Morvan, Maria del Pilar Schneider, Mariana Guergova-Kuras, Ariana Pharma.

“LBA2: Text mining workflow for extraction of paragraphs from full articles describing drug-gene interactions to support Onco KEM software platform for personalized treatments”, Fanny Perraudeau, David Morley, Mohammad Afshar, Mariana Guergova-Kuras, Ariana Pharma.

Links: WIN 2014 conference website | Download P2.26 PDF | Download LBA2 PDF

APS 2013: 33rd Annual Scientific Meeting of the Australian Pain Society, 17-20 March 2013, Canberra, Australia

“Which baseline characteristics influence the response to milnacipran (Joncia®) in patients with fibromyalgia?”, O Vitton, P Bunouf, F Bonfils and L Girard, Pierre Fabre Research & Development Center, Toulouse, France.

Links: APS 2013 conference website | Download poster PDF

48th Annual Meeting of the EASL, April 2013, Amsterdam, The Netherlands

“A 4 serum protein signature for the diagnosis of mild fibrosis in chronic Hepatitis C (Hepachronix study)”, B Jardin Watelet, I Bieche, M Lapalus, A Duces, E Mathieu-Dupas, S De Muynck, N Lambert, I Baxtelli-Molina, B Sallenave, E Nicolas, E Estrabaud, N Jullian, J Balicchi, M Martinot-Peignoux, O Lada, V Paradis, D Valla, P Bedossa, D Laune, P Marcellin, M Vidaud, T Asselah*.

Links: EASL 2013 conference website

The Liver Meeting 2012, November 2012, Boston, Massachussets, USA

“A liver gene molecular study rational to identify serum proteins signature to predict treatment response in chronic Hepatitis C”, T Asselah, I Bieche, I Molina, A Duces, M Lapalus, S De Muynck, E Mathieu-Dupas, N Jullian, N Lambert, D Laune, E Nicolas, B Sallenave, M Blanuet, M Estrabaud, S Pawlowski, V Moulin, M Martinot-Peignoux, O Lada, D Valla, P Bedossa, B Jardin-Watelet, P Marcellin, M Vidaud.

“Liver gene expression rational to build a serum proteins signature of mild fibrosis in chronic hepatitis C”, B Jardin-Watelet, I Bieche, M Lapalus, A Duces, EM Dupas, S De Muynck, N Lambert, I Molina, B Sallenave, E Nicolas, E Estrabaud, N Jullian, J Balicchi, M Martinot-Peignoux, O Lada, V Paradis, D Valla, P Bedossa, D Laune, P Marcellin, M Vidaud, T Asselah.

19th International Symposium on Hepatitis C Virus and Related Viruses, October 2012, Venice, Italy

47th Annual Meeting of the EASL, April 2012, Barcelona , Spain

“A four Gene molecular signature is better than IL28B polymorphism to predict treatment response to pegylated –interferon and ribavirin in chronic hepatitis C”, T Asselah, I Bieche, B Jardin-Watelet, A Duces, M Lapalus, S De Muynck, E Dupas, N Jullian, I Molina, N Lambert, E Nicolas, B Sallenave, M Blanuet, E Estrabaud, M Martinot-Peignoux, O Lada, D Valla, P Bedossa, D Laune, P Marcellin, M Vidaud.

18th International Symposium on Hepatitis C Virus and Related Viruses, September 2011, Seattle, Washington USA

Digestive Disease Week, May 2010, New Orleans, LA

“Liver gene expression signature of mild fibrosis in chronic hepatitis C”, A Ducès, M Lapalus, I Bièche, B Jardin Watelet, E Dupas, S De Muynck, I Molina, N Lambert, B Sallenave, E Nicolas, E Estrabaud, N Jullian, M Martinot-Peignoux, O Lada, V Paradis, D Valla, P Bedossa, D Laune, M Vidaud, P Marcellin, T Asselah.

45th Annual Meeting of the EASL, April 2010, Vienna, Austria

“Liver gene expression signature to predict response to pegylated interferon plus ribavirin in chronic hepatitis C”, A Ducès, I Bièche, B Jardin-Watelet, M Lapalus, S De Muynck, E Dupas, I Molina, N Lambert, E Nicolas, B Sallenave, E Estrabaud, N Jullian, M Martinot-Peignoux, O Lada, V Paradis, D Valla, P Bedossa, D Laune, M Vidaud, P Marcellin, T Asselah.


Publications


Patient Stratification using KEM


“Is the Efficacy of Milnacipran in Fibromyalgia Predictable? A Data-Mining Analysis of Baseline and Outcome Variables”, L Abtroun, P Bunouf, RM Gendreau and O Vitton, Clin. J. Pain, 32 (2016) 435–440.

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Formal Concept Analysis


For a recent review of FCA, see Proceedings of the 10th International Conference on Formal Concept Analysis, ICFCA 2012, Leuven, Belgium, May 7-10, 2012, F Domenach, D Ignatov and J Poelmans (Eds.), Lecture Notes in Computer Science / Lecture Notes in Artificial Intelligence, 7278 (2012).

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“Human Discovery and Machine Learning”, C Dartnell, E Martin, H Hagège and J Sallantin, International Journal of Cognitive Informatics and Natural Intelligence, 2 (2008) 55-69.

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“Multiobjective/Multicriteria Optimization and Decision Support in Drug Discovery”, M Afshar, A Lanoue and J Sallantin, Comprehensive Medicinal Chemistry II, 4 (2006) 767-774.

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“A pragmatic logic of scientific discovery”, J Sallantin, C Dartnell, and M Afshar in Proceedings of the 9th International Conference on Discovery Science, DS 2006, Barcelona, Spain, Oct 7-10, 2006, N Lavrač, L Todorovski and KP Jantke (Eds.), Lecture Notes in Computer Science / Lecture Notes in Artificial Intelligence, 4265 (2006) 231-242.

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KEM citations

Publications from other research groups that have cited KEM. “Automating Knowledge Discovery for Toxicity Prediction Using Jumping Emerging Pattern Mining”, R Sherhod, VJ Gillet, PN Judson and JD Vessey, J. Chem. Inf. Model., 52 (2012) 3074-87.

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Systems Biology, Drug Repositioning

“The CancerCell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity”, Nature, 483 (2012) 603–607.

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“Systematic identification of genomic markers of drug sensitivity in cancer cells”, Nature, 483 (2012) 570-575.

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“Navigating the kinome”, Nature Chemical Biology, 7 (2011) 200-202.

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“Predicting new molecular targets for known drugs”, Nature, 462 (2009) 175-181.

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“A quantitative analysis of kinase inhibitor selectivity”, Nature Biotechnology, 26 (2008) 127–132.

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