Predicting disease severity in Multiple Sclerosis using multimodal data and machine learning

Author:

Andorra Magi1,Freire Ana2,Zubizarreta Irati1,de Rosbo Nicole Kerlero3,Bos Steffan D.4,Rinas Melanie5,Høgestøl Einar A.4,Benavent Sigrid A. Rodez4,Berge Tone6,Brune-Ingebretse Synne4,Ivaldi Federico3,Cellerino Maria3,Pardini Matteo7,Vila Gemma1,Pulido-Valdeolivas Irene1,Martinez-Lapiscina Elena H.1,Llufriu Sara1,Saiz Albert1,Blanco Yolanda1,Martinez-Heras Eloy1,Solana Elisabeth1,Bäcker-Koduah Priscilla8,Behrens Janina8,Kuchling Joseph8,Asseyer Susanna8,Scheel Michael8,Chien Claudia8,Zimmermann Hanna8,Motamedi Seyedamirhosein8,Kauer-Bonin Joseph8,Brandt Alex8,Saez-Rodriguez Julio5,Alexopoulos Leonidas9,Paul Friedemann8,Harbo Hanne F4,Shams Hengameh10,Oksenberg Jorge10,Uccelli Antonio7,Baeza-Yates Ricardo2,Villoslada Pablo1

Affiliation:

1. Institut d’Investigacions Biomediques August Pi Sunyer (IDIBAPS) and Hospital Clinic

2. Pompeu Fabra University

3. University of Genoa

4. University of Oslo

5. Heidelberg University

6. Oslo University Hospital

7. IRCCS Ospedale Policlinico San Martino Genoa

8. Charité Universitaetsmedizin Berlin

9. ProtATonce Ltd

10. University of California, San Francisco

Abstract

Abstract Background Multiple Sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging, and multimodal biomarkers to define the risk of disease activity. Methods We have analyzed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centers, collecting disability scales at baseline and 2 years later. Imaging data included brain MRI and optical coherence tomography, and omics included genotyping, cytomics and phosphoproteomic data from peripheral blood mononuclear cells. Predictors of clinical outcomes were searched using Random Forest algorithms. Validation was conducted in an independent prospective cohort of 271 MS patients from a single center. Results We found algorithms for predicting confirmed disability accumulation for the different scales, No Evidence of Disease Activity (NEDA), onset of immunotherapy and the escalation from low- to high-efficacy therapy with intermediate to high-accuracy. This accuracy was achieved for most of the predictors by using clinical data alone or in combination with imaging data. Still, in some cases, the addition of omics data slightly increased algorithm performance. Accuracies were comparable in the discovery and validation cohorts. Conclusion Combining clinical, imaging, and omics data with machine learning helps to identify MS patients at risk of disability worsening.

Publisher

Research Square Platform LLC

Reference56 articles.

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2. Precision medicine for multiple sclerosis: an update of the available biomarkers and their use in therapeutic decision making;Pulido-Valdeolivas I;Expert Rev Precis Med Drug Dev,2017

3. Villoslada P. Personalized medicine for multiple sclerosis: How to integrate neurofilament light chain levels in the decision? Mult Scler. 2021: 13524585211049552.

4. Pitt D, Lo CH, Gauthier SA, et al. Toward Precision Phenotyping of Multiple Sclerosis. Neurology(R) neuroimmunology & neuroinflammation. 2022; 9.

5. A brief history of NEDA;Giovannoni G;Multiple sclerosis and related disorders,2018

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