Development of comer score a new tool to predict covid 19 TNT phu

Development of CoMeR score: A new tool to predict Covid-19 infection severity Presented by Nguyen-Trong-Phu Tran Dec 24th, 2022 Nguyen-Trong-Phu Tran1,2, Ba-Thien Tran3 Thi-Thanh-Khuong Tran3, and Phuc-Loi Luu4,5* 1Can Tho University of Medicine and Pharmacy, Can Tho city 90000, Vietnam Medicine, Chulalongkorn University, Thailand 3Department of Molecular Biology, Institute Of Food And Biotechnology, Can Tho University, Can Tho city 90000, Vietnam 4Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney 2010, New South Wales, Australia 5St Vincent's Clinical School, UNSW Sydney, 2010, New South Wales, Australia 2Faculty of NO CONFLICTS OF INTEREST TO DECLARE Outline • Background: Covid-19, Epigenetics and Epigenomics • Objectives • Methods • Results and discussions • Conclusion BACKGROUND Covid-19 and the need to early predict severe cases 262 million cases 5.21 million deaths Nov 30, 2021 → Biomarker for stratifying severe cases vs other phenotypes → Reduce healthcare burden Previous Studies Asgari, S., & Pousaz, L A (2021) Human genetic variants identified that affect COVID susceptibility and severity Polygenic Risk Score for Admixed Americans were predictive for COVID-19 severity AUC = 0.54 (adapted from preliminary results of Christopher H) 10.1007/s10557-020-07105-7 BACKGROUND Epigenetics and epigenomics What is Epigenetics? Your genes play an important role in your health Awomanwithouthermanisnothing Your behaviors and environment can cause changes that affect the way your genes work A woman, without her man, is nothing A woman: without her, man is nothing 10.3892/br.2016.781 Input: Epigenomic data Output: CoMeR score Filtering: P 0.15 => 32 DMPs Input: Epigenomic data Output: CoMeR score 32 DMPs Feature Selection best DMPs Input: Epigenomic data Output: CoMeR score 𝐂𝐨𝐌𝐞𝐑 �𝐜𝐨�𝐞 = 6.9642 − 3.2855 × 𝜷� − 6.7090 × 𝜷� − 6.3302 × 𝜷 � DMP CHR POSITION MEAN DIFF GENE (Severe/non.Severe) 𝛽1 cg13452062 chr1 79088559 -0.223 IFI44L 𝛽2 cg07189579 chr8 134258444 -0.109 NDRG1 𝛽3 cg22652934 chr21 36180035 -0.088 RUNX1 CoMeR score – the new tool CoMeR score RESULTS 4.2 Evaluating the predictive performance of CoMeR score Input: Epigenomic data CoMeR score Validate on testing set AUC, accuracy Validate on an independent cohort AUC, accuracy Evaluation on testing set True class Severe Non severe Severe 35 79 Non severe 14 343 AUC=0.85 Evaluation on independent validation set True class Severe Non severe Severe 51 15 Non severe 15 45 AUC=0.83 Input: Epigenomic data CoMeR score Validate on testing set AUC = 0.85 Validate on an independent cohort AUC = 0.83 Polygenic Risk Score for Admixed Americans were predictive for COVID-19 severity AUC = 0.54 (adapted from preliminary results of Christopher.H) 10.1007/s10557-020-07105-7 CoMeR score is correlated with COVID-19 GRAM risk score Based on 10 clinical factors • Chest radiographic abnormality • Age • Hemoptysis • Dyspnea • Unconsciousness • Number of comorbidities • Cancer history • Neutrophil-to-lymphocyte ratio • Lactate dehydrogenase • Direct bilirubin → AUC = 0.88 RESULTS 4.3 To facilitate the application of CoMeR Future direction: CoMeR score for diagnosis of COVID-19 patient severity in clinic Multiplex bisulfite ddPCR with amplicons Blood sample Predict Compute CoMeR score B-value of CpG sites CoMeR score Severe/non Severe 37 Patient_ID Cg01 Cg02 Cg03 XYZ 0.34 0.84 0.53 Patient_ID Cg01 Cg02 Cg03 CoMeR score XYZ 0.34 0.84 0.53 0.79 Predicted Severe CONCLUSION CONCLUSION • Our work represents CoMeR score - a simplified new tool with good performance in predicting severe Covid-19 infection patients at admission • Future studies are needed to validate our tool in other different populations with Covid-19 infections