Multidisciplinary Institute in Artificial intelligence

DESCRIPTION

The production of biological data has achieved unprecedented levels. On a single specimen, uncountable variables are generated by a single “omic” experiment, while several of them are already used in medical researches: genomics (DNA- or whole-genome sequencing), epigenomics (methylated-DNA-, RNA-, Chromatin-IP-, ATAC-sequencing, etc.), metabolomics, lipidomics, proteomics and others. Beside these multiple “omics”, in vivo imaging technologies and high-throughput environmental exposure data are also available. Relating high throughput data to health status unleash new opportunities, to understand molecular mechanisms of diseases or to provide biomarkers for disease prediction, management and prognosis. However, general-purpose AI methodologies need to be adapted to face the numerous machine learning issues raised when investigating relationships between biological features and phenotypes: small sample size (w. r. t. number of features), confounding variables, very low signal /noise ratio, and need for interpretability (confusion between causation and correlation). In this research chair, we ambition to investigate methodological issues, which are specific to omics data, in order to implement efficient machine learning solutions in biomedical research programs.

ACTIVITIES

First, we seek to develop new methods to relate high-dimensional genomic features to high dimensional phenotypic obtained with Magnetic Resonance Imaging techniques (MRI). Machine learning techniques will be based on multi-constrained models that include spatial coherence for MRI and sparseness constraint for genotypes. The chair will leverage data from the national pilot program of Plan France Médecine Génomique 2025 on 1500 individuals (multimodal health data and Electronic Health Record - EHR) with intellectual disability. In this program, referred to as DEFIDIAG, (1) AVIESAN will provide whole-genome sequencing data in 2020. (2) A network of clinical geneticists from the French healthcare pathway for rare disorders with multiple congenital anomalies and intellectual disability (www.anddi-rares.org) will expertise the 1500 patients. (3) Raw brain MRI will be gathered in a national repository. This unique dataset will make it possible to learn accurate prioritization of genomic variants through the analysis of phenotypic data from EHR and from raw brain MRI signals.

Second, the chair will leverage the unique Grenoble position in the field of mass spectrometry (MS) based omics (proteomics, metabolomics, lipidomics): The Proteomics French national Infrastructure (www.profi-proteomics.fr), as well as its computational work-package are both coordinated by the Grenoble partner lab. In addition, a metabolomics/lipidomics platform is emerging as a joint effort of IAB lab, TIMC lab and CHUGA. MS-based sequencing is recent (compared to other omics) and its data processing is still hindered by open questions (non-exhaustive coverage, instrumental sources of data corruption, multiplexed acquisitions, occurrence and nature of missing values, etc.). Among these questions, we will investigate data disentangling methods to improve the capability of multiplexed MS acquisitions, leading to more accurate quantifications and deeper coverage.

Finally, outreach and education actions will be conducted: our industrial partners will foster the transfer of machine learning tools into routine medical practice (Genetic department of CHUGA). Software tools and data science know-how transfer will be organized, to bring most recently emerging omics technology to state-of-the-art data processing practices. Finally, a national educational program in medical data science for future physicians is already under construction.

CHAIR EVENTS

3ième Journée Intégrative de Protéomique et Métabolomique, Lyon, 2020.
• Conférence Midi-Minatec (pending to unlock-down)

SELECTED LIST OF PUBLICATIONS 

• Olga Permiakova, Romain Guibert, Alexandra Kraut, Thomas Fortin, Anne-Marie Hesse et al. CHICKN: extraction of peptide chromatographic elution profiles from large scale mass spectrometry data by means of Wasserstein compressive hierarchical cluster analysis. BMC Bioinformatics, BioMed Central, 2021, 22 (1), 

• Olga Permiakova, Thomas Burger. Sketched Stochastic Dictionary Learning for large‐scale data and application to high‐throughput mass spectrometry. Statistical Analysis and Data Mining: The ASA Data Science Journal, 2021, 

• Hélène Borges, Anne-Marie Hesse, Alexandra Kraut, Yohann Couté, Virginie Brun et al. Well Plate Maker: A user-friendly randomized block design application to limit batch effects in largescale biomedical studies. Bioinformatics, Oxford University Press (OUP), 2021.

• T. Crespy, M. Durost, P. Fricault, B. Lemasson, P. Bouzat, E. L. Barbier, J.-F. Payen. Hypertonic sodium lactate to alleviate functional deficits following diffuse traumatic brain injury: an osmotic or a lactate-related effect? Neurocritical Care. Early view.

• S. Hamelin, V. Stupar, L. Mazière, J. Guo, W. Labriji, C. Liu, L. Bretagnolle, S. Parrot, E. L. Barbier, A. Depaulis*, F. Fauvelle*. In vivo GABA increase as a biomarker of the epileptogenic zone: an unbiased metabolomics approach. Epilepsia, 62(1);163-175, 2021.

• H. Borges, A.-M. Hesse, A. Kraut, Y. Couté, V. Brun, T. Burger. "Well Plate Maker: A user-friendly randomized block design application to limit batch effects in large-scale biomedical studies". Bioinformatics, btab065, 2021.

• O. Permiakova, R. Guibert, A. Kraut, T. Fortin, A.-M. Hesse, T. Burger. "CHICKN: Extraction of peptide chromatographic elution profiles from large scale mass spectrometry data by means of Wasserstein compressive hierarchical cluster analysis". BMC Bioinformatics, in press, 2021.

• Aurélien Delphin, Fabien Boux, Clément Brossard, Jan Warnking, Benjamin Lemasson et al. Towards optimizing MR vascular fingerprinting. ISMRM & SMRT Virtual Conference & Exhibition, May 2021, Vancouver, Canada.

• Fabien Boux, Florence Forbes, Julyan Arbel, Benjamin Lemasson, Emmanuel L Barbier. Bayesian inverse regression for vascular magnetic resonance fingerprinting. IEEE Transactions on Medical Imaging, Institute of Electrical and Electronics Engineers, 2021, 40 (7), pp.1827-1837.

• Fabien Boux, Florence Forbes, Nora Collomb, Emma Zub, Lucile Maziere et al. Neurovascular multiparametric MRI defines epileptogenic and seizure propagation regions in experimental mesiotemporal lobe epilepsy. Epilepsia, Wiley, 2021, 62 (5), pp.1244-1255.

• Wesley J. Delage, Julien Thevenon & Claire Lemaitre, Towards a better understanding of the low recall of insertion variants with short-read based variant callers, BMC Genomics.

• ESHG 2021 (Yauy et al.)

• JOBIM (Testard et al.)

• ACLF, (Yauy et al.)

•  A. Attyé, S. Cackowski, A. Tucholka, P. Roca, P. Rubini, S. Verclytte, L. Colas, J. Ding, J.-F. Budzik, F. Renard, E. L Barbier, R. Casey, S. Vukusic, F. Cotton. Breaking the clinico-radiological paradox in multiple sclerosis using machine learning. Proceedings 28th Annual Meeting ISMRM, 2020, Sidney (Australia).

• B. Meyer, L. Hirschler, J. Warnking, E. Barbier, M. Budde. Preclinical Spinal Cord Perfusion Imaging with Pseudo-Continuous Arterial Spin Labeling. Proceedings 28th Annual Meeting ISMRM, 2020, Sidney (Australia).

• C. Brossard, O. Montigon, F. Boux, A. Delphin, T. Christen, E. L Barbier, Benjamin Lemasson*. MP3: Medical software for Processing multi-Parametric images Pipelines, Frontiers Neuroinformatics. 14:594799, 2020.

• J.-F. Payen, M. Richard, G. Francony, G. Audibert, E. L. Barbier, N. Bruder, C. Dahyot-Fizelier, T. Geeraerts, L. Gergele, L. Puybasset, B. Vigue, K. Skaare, J.-L. Bosson, P. Bouzat. Comparison of strategies for monitoring and treating patients at the early phase of severe traumatic brain injury: The multicentre randomized controlled OXY-TC trial study protocol. BMJ Open, 10:e040550, 2020.

• P. Roca, A. Attyé, L. Colas, A. Tucholka, P. Rubini, S. Cackowski, J. Ding, J.-F. Budzik, F. Renard, S. Doyle, E. L. Barbier, I. Bousaid, R. Casey, S. Vukusic, N. Lassau, S. Verclytte, F. Cotton; OFSEP Investigators;Steering Committee; Investigators; Imaging group. Artificial intelligence to predict clinical disability in patients with multiple sclerosis using FLAIR MRI. Diagnostic and Interventional Imaging. S2211-5684(20)30155-8, 2020 

• C. Verry, S. Dufort, B. Lemasson, S. Grand, J. Pietras, I. Troprès, Y. Crémillieux, F. Lux, S. Mériaux, B. Larrat, J. Balosso, G. Le Duc, E. L. Barbier, O. Tillement. Targeting brain metastases with ultrasmall theranostic nanoparticles, a first-in-human trial from an MRI perspective. Science Advances, 6(29), eaay5279, 2020.

• G. J.-P. C. Becq, E. L. Barbier, S. Achard. Brain networks of rats under anesthesia using resting-state fMRI: comparison with dead rats, random noise and generative models of networks. Journal of Neural Engineering, 17(4):045012, 2020.

• Cancé C, Madiot PE, Lenne C, Artemova S, Cohard B, Bodin M, Caporossi A, Blatier JF, Fauconnier J, Olive F, Pagonis D, Le Magny D, Bosson JL, Charriere K, Paturel I, Lavaire B, Schummer G, Eterno J, Ravey JN, Bricault I, Ferretti G, Chanoine S, Bedouch P, Barbier E, Thevenon J, Mossuz P, Moreau-Gaudry A. Cohort Creation and Visualization Using Graph Model in the PREDIMED Health Data Warehouse. Stud Health Technol Inform., 270:108-112, 2020.

• G. J.-P. C. Becq, T. Habet, N. Collomb, M. Faucher, C. Delon-Martin, V. Coizet, S. Achard*, E. L. Barbier*. Functional connectivity is preserved but reorganized across several anesthetic regimes. Neuroimage, 219:116945, 2020.

• Tristan T. Deruelle, F. Kober, A. Perles-Barbacaru, T. Delzescaux, V. Noblet, E. L Barbier, M. Dojat. A Multicenter Preclinical MRI Study: Definition of Rat Brain Relaxometry Reference Maps. Frontiers in Neuroinformatics, 14:22, 2020.

• L. Hirschler, N. Collomb, J. Voiron, S. Köhler, E. L. Barbier, J. M. Warnking. SAR comparison between CASL and pCASL at high magnetic field and evaluation of the benefit of a dedicated labeling coil. Magnetic Resonance in Medicine 83(1):54-261, 2020.

• M. Lacombe, M. Jaquinod, L. Belmudes, Y. Couté, C. Ramus, F. Combes, T. Burger, E. Mintz, J. Barthelon, V. Leroy, A. Poujois, A. Lachaux, F. Woimant, V. Brun. "Comprehensive and comparative exploration of the Atp7b-/-mouse plasma proteome". Metallomics, 12(2), pp 249-258, 2020.

• Y. Couté, C. Bruley, T. Burger. "Beyond target-decoy competition: stable validation of peptide and protein identifications in mass spectrometry-based discovery proteomics". Analytical Chemistry, 92(22), pp 14898–14906, 2020.

• A. T. Pagnamenta, P. Heemeryck, H. C. Martin, C. Bosc, I. Uszynski, S. Gory-Fauré, S. Couly, C. Deshpande, A. Siddiqui, A. A. Elmonairy, WGS500 consortium, 100,000 Genomes Project, S. Jayawant, S. Murthy, I. Walker, L. Loong, P. Bauer, F. Vossier, E. Denarier, T. Maurice, E. L. Barbier, J.-C. Deloulme, J. C. Taylor, E. M. Blair, A. Andrieux, M-Jo Moutin. Defective tubulin detyrosination causes structural brain abnormalities with cognitive deficiency in humans and mice. Human Molecular Genetics 28(20):3391-3405, 2019.

• N. Coquery, J.-F. Adam, C. Nemoz, R. Janvier, J. Livingstone, A. Chauvin, S. Kefs, C. Guerineau, L. de Saint Jean, A. Bouchet, S. Bartzsch, E. Schültke, A. Siegbahn, E. Bräuer-Krisch, B. Lemasson, E. L. Barbier, J. Laissue, J. Balosso, D. Val-Laillet, R. Serduc. Locomotion and eating-behaviour changes of the Yucatan minipig model after unilateral radio-induced ablation of the caudate nucleus. Scientific Reports. 9(1):17082, 2019.

• F. Natali, C. Dolce, J. Peters, C. Stelletta, B. Demé, J. Ollivier, G. Leduc, A. Cupane, E. L. Barbier. Brain lateralization probed by water diffusion at the atomic to micrometric scale. Scientific reports 9:14694, 2019.

• W. Klement, M. Blaquiere, E. Zub, F. deBock, F. Boux, E. Barbier, E. Audinat, M. Lerner-Natoli, N. Marchi. A pericyte-glia scarring develops at the leaky capillaries in the hippocampus during seizure activity. Epilepsia 60(7):1399-1411, 2019.

• F. Natali, C. Dolce, J. Peters, C. Stelletta, B. Demé, J. Ollivier, M. Boehm, G. Leduc, I. Piazza, A. Cupane, E. L. Barbier. Anomalous water dynamics in brain: a combined diffusion Magnetic Resonance Imaging and Neutron Scattering investigation. Journal of the Royal Society Interface 16(157):20190186, 2019.

• S. Dufort, G. Appelboom, C. Verry, E. L. Barbier, F. Lux, E. Brauer-Krisch, L. Sancey, S. D. Chang, M. Zhang, S. Roux, O. Tillement, G. Le Duc. Ultrasmall theranostic gadolinium-based nanoparticles improve high-grade rat glioma survival. Journal of Clinical Neuroscience, 67;215-219. 2019.

• O. F. Eker, R. Ameli, N. Makris, T. Jurkovic, O. Montigon, E. L. Barbier, T. H. Cho, N. Nighoghossian, Y. Berthezène. MRI Assessment of Oxygen Metabolism and Hemodynamic Status in Symptomatic Intracranial Atherosclerotic Stenosis: A Pilot Study. J Neuroimaging 29(4), 467-475, 2019.

• H. Borges, R. Guibert, O. Permiakova, T. Burger. "Distinguishing between spectral clustering and cluster analysis of mass spectra". Journal of Proteome Research, 18(1), pp 571–573, 2019.

• S. Wieczorek, Q. Giai Gianetto, T. Burger. "Five simple yet essential steps to correctly estimate the rate of false differentially abundant proteins in mass spectrometry analyses". Journal of Proteomics, vol. 207, p. 103441, 2019.

• C. Verry, S. Dufort, B. Lemasson, S. Grand, Y. Crémillieux, F. Lux, S. Mériaux, B. Larrat, J. Balosso, G. Le Duc, E. L. Barbier, O. Tillement. MR imaging of theranostic Gd-based Aguix nanoparticles in patients with 4 histological types of brain metastasis. Proceedings Contrast Media Research Symposium, 2019, Erice (IT)

• S. Artemova, P.-E. Madiot, A. Caporossi, PREDIMED group, P. Mossuz, A. Moreau-Gaudry. PREDIMED – Clinical Data Warehouse of Grenoble Alpes University Hospital. Proceedings MEDINFO 2019, Lyon, France

• C. Verry, S. Dufort, B. Lemasson, S. Grand, Y. Crémillieux, F. Lux, S. Mériaux, B. Larrat, J. Balosso, G. Le Duc, E. L. Barbier, O. Tillement. First-in-human trial of Gd-based theranostic nanoparticles: MRI assessment of uptake and biodistribution in patients with multiple brain metastases. Proceedings EMIM, 2019, Glasgow (UK)

• S. Dufort, C. Verry, B. Lemasson, S. Grand, Y. Crémillieux, F. Lux, S. Mériaux, B. Larrat, J. Balosso, G. Le Duc, E. L. Barbier, O. Tillement. First-in-human trial of Gd-based theranostic nanoparticles: MRI assessment of uptake and biodistribution in patients with multiple brain metastases. Proceedings 27th Annual Meeting ISMRM, 2019, Montreal (Canada).