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 Tran 1,2 , Ba-Thien Tran 3 Thi-Thanh-Khuo

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 Tran 1,2 , Ba-Thien Tran 3 Thi-Thanh-Khuong Tran 3 , and Phuc-Loi Luu 4,5*

1 Can Tho University of Medicine and Pharmacy, Can Tho city 90000, Vietnam.

2 Faculty of Medicine, Chulalongkorn University, Thailand

3 Department of Molecular Biology, Institute Of Food And Biotechnology, Can Tho University, Can Tho city 90000, Vietnam.

4 Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney 2010, New South Wales, Australia.

5 St Vincent's Clinical School, UNSW Sydney, 2010, New South Wales, Australia.

NO CONFLICTS OF INTEREST

TO DECLARE

1 BACKGROUND

Covid-19 and the need to early predict severe cases

Nov 30, 2021

262 million cases

5.21 million deaths

→ 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

1 BACKGROUND

Epigenetics and epigenomics

What is Epigenetics?

Your genes play an important role in your health

10.3892/br.2016.781

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

Awomanwithouthermanisnothing

Identical twins come from the same fertilized egg

→ share identical genetic profiles (genome)

Identical twins' differences focus of epigenetics studies | CBC News

→ Behavioral and environmental impact may vary the way your genes work

Linda Lewis(leukemia)Leora Eisen

Example: Identical twins

DNA Methylation?

Genome-wide DNA methylation (Epigenome)?

https://en.wikipedia.org/wiki/DNA_methylation

2 OBJECTIVES

1 Developing a COVID-19 Methylation risk (CoMeR) score for SeverityClassification

2 Evaluating the predictive performance of CoMeR score

3 Characterization of CoMeR score

4 ShinyApp to facilitate the application of CoMeR score

3 METHODS

Materials and methods

• Study design: a patient-level meta-analysis of epigenomic and clinical

data of Covid-19 patients and healthy controls

• Subjects of interest: Adults (754 covid-19 patients and 950 controls)

Validation cohort Discovery cohort

WORKFLOW

Data table after processed

690285 rows

754 covid-19 patients and 950 controls

Beta values (proportion of methylation at one specific site)

patient 1

patient 2

4 RESULTS

4 RESULTS

1 Development of CoMeR score

Controls Mild Severe P-value and R2 from Linear regression model

Severity = intercept + cg[i] + age + sex

significant values

=> 32 DMPs

DMPs

3 best DMPs

CoMeR score – the new tool

DMP CHR POSITION MEAN DIFF

CoMeR score

4 RESULTS

4.2 Evaluating the predictive performance of CoMeR score

1 2 3 4 5 6

Input:

Epigenomic data

CoMeR score

Validate on testing set Validate on an independent cohort

Evaluation on testing set

Polygenic Risk Score for Admixed Americans were predictive for

CoMeR score is correlated with COVID-19 GRAM risk score

Based on 10 clinical factors

• Chest radiographic abnormality

4 RESULTS

4.3 To facilitate the application of CoMeR

Blood sample B-value of 3CpG sites CoMeRscore Severe/non Severe

Multiplex bisulfite ddPCR with 3 amplicons Compute CoMeR score Predict

5 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