Predicting and elucidating the etiology of fatty liver disease using a machine learning-based approach: an IMI DIRECT study
By
Naeimeh Atabaki-Pasdar,
Mattias Ohlsson,
Ana Viñuela,
Francesca Frau,
Hugo Pomares-Millan,
Mark Haid,
Angus G Jones,
E Louise Thomas,
Robert W Koivula,
Azra Kurbasic,
Pascal M Mutie,
Hugo Fitipaldi,
Juan Fernandez,
Adem Y Dawed,
Giuseppe N Giordano,
Ian M Forgie,
Timothy J McDonald,
Femke Rutters,
Henna Cederberg,
Elizaveta Chabanova,
Matilda Dale,
Federico De Masi,
Cecilia E Thomas,
Kristine H Allin,
Tue H. Hansen,
Alison Heggie,
Mun-Gwan Hong,
Petra JM Elders,
Gwen Kennedy,
Tarja Kokkola,
Helle Krogh Pedersen,
Anubha Mahajan,
Donna McEvoy,
Francois Pattou,
Violeta Raverdy,
Ragna S. Häussler,
Sapna Sharma,
Henrik S Thomsen,
Jagadish Vangipurapu,
Henrik Vestergaard,
Leen M ‘t Hart,
Jerzy Adamski,
Petra B Musholt,
Soren Brage,
Søren Brunak,
Emmanouil T. Dermitzakis,
Gary Frost,
Torben Hansen,
Markku Laakso,
Oluf Pedersen,
Martin Ridderstråle,
Hartmut Ruetten,
Andrew T Hattersley,
Mark Walker,
Joline WJ Beulens,
Andrea Mari,
Jochen M Schwenk,
Ramneek Gupta,
Mark I. McCarthy,
Ewan R Pearson,
Jimmy D Bell,
Imre Pavo,
Paul W Franks
Posted 11 Feb 2020
medRxiv DOI: 10.1101/2020.02.10.20021147
BackgroundNon-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in type 2 diabetes (T2D) and beyond. Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and ultimately hepatocellular carcinomas. Methods and FindingsUtilizing the baseline data from the IMI DIRECT participants (n=1514) we sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. Multi-omic (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, and measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI image-derived liver fat content (<5% or [≥]5%). We applied LASSO (least absolute shrinkage and selection operator) to select features from the different layers of omics data and Random Forest analysis to develop the models. The prediction models included clinical and omics variables separately or in combination. A model including all omics and clinical variables yielded a cross-validated receiver operator characteristic area under the curve (ROCAUC) of 0.84 (95% confidence interval (CI)=0.82, 0.86), which compared with a ROCAUC of 0.82 (95% CI=0.81, 0.83) for a model including nine clinically-accessible variables. The IMI DIRECT prediction models out-performed existing non-invasive NAFLD prediction tools. ConclusionsWe have developed clinically useful liver fat prediction models (see: www.predictliverfat.org) and identified biological features that appear to affect liver fat accumulation.
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